Compositions comprising alditol and alditol derivates for supporting and protecting the skin

Abstract

A topical composition, preferably an emulsion or wash, more preferably a (W / O) emulsion, (O / W) emulsion or wash, for use on the skin comprising: a. 0.01 to 8.00% of a selective prebiotic comprising: i. Xylitol, ii. Anhydroxylitol, and iii. Xylitylglucoside, b. at least one humectant, c. at least one provitamin, vitamin and / or vitamin derivate from provitamin, vitamin B3 and / or a salt thereof, preferably niacinamide, provitamin, vitamin B5 and / or a salt thereof, preferably dexpanthenol and / or provitamin, vitamin E and / or a salt thereof, preferably tocopheryl acetate, and d. at least two lipids from the list comprising or consisting of ceramides, cholesterol, cholesterol esters, triglycerides, free fatty acids, free fatty acid derivates including glyceryl oleate and ethyl linoleate, caprylic capric triglyceride, Butyrospermum parkii (shea) butter, shea butter derivatives, squalane and / or squalene. Said composition for use in the treatment and / or prevention of an acne and / or an eczema skin disease. Non-therapeutic use of said composition for strengthening the physical, biochemical and microbial layer of the skin, wherein the skin is newborn, infant, child, adolescent, adult or mature, preferably newborn and / or infant skin.

Description

[0001] BYH240210 FC -1-

[0002]

[0003] alditol and alditol derivates for

[0004]

[0005] and protecting the skin

[0006] Description

[0007] Disclosed herein are compositions that can support a local microenvironment in a subject by selective supporting the growth of beneficial bacteria and / or reduce the growth of opportunistic pathogens and / or pathogens. The disclosure relates to compositions for supporting and protecting the skin, in particular the skin of newborns and infants by fostering a beneficial skin microbiome.

[0008] TECHNICAL FIELD

[0009] The present disclosure relates to the field of microbiology, more particular to supporting the selective growth of host beneficial bacteria, and specifically to supporting the growth of host beneficial bacteria with compositions comprising alditols and their derivates.

[0010] BACKGROUND

[0011] The relevance of the microbiome in humans and animals and their location specific composition has been increasingly revealed in the past decade. Among other insights it has been discovered that the microbiome or microbiota compositions are specific to their location but that the different microbiomes share functions such as the breakdown of molecules, the protection from invading pathogens and the education of the host’s immune system.

[0012] The compositions of the microbiomes are affected in their assembly, stability and function by factors stemming from the host, the specific location of the host, environmental factors and / or the interactions with other members of the microbiome. The interactions of the members of the microbiome can act competitively to exclude one another, neutrally or synergistically for mutual benefits. The individual members of the microbiome can have different effects on the host acting as pathogens, opportunistic pathogens or commensals.

[0013] The skin is part of the integumentary system that encloses the body and a particular microbiota site. The skin is an essential organ with versatile functions. Among those it protects the body from external influences such as irritants, antigens and allergens. The skin’s functional composition is comprised of biological or microbiome, physical and biochemical functions or barriers provided by different constituents of the skin.BYH240210 FC -2- The biological function is provided by the skin’s microbiome, also known as skin flora or microbiota, the millions of bacteria, archaea, protists, viruses and fungi that reside on the skin. The physical barrier is localized primarily in the stratum corneum (SC) and the epidermis. In the SC physical barrier function is provided by cells which are rich in proteins the so called comeocytes with a cornified enveloped and cytoskeleton which are held together by comeodesmosomes and intercellular domains which are rich in lipids in particular ceramides. The tight, gap and adherens junctions, desmosomes and cytoskeletal elements of the epidermis as well as the lipids synthesized and secreted by the keratinocytes of the epidermis contribute to the physical barrier function of the skin. The biochemical function is mediated by several (bio)chemical factors and (bio)chemical homeostasis processes, which inter alia ensure that transepithelial water loss (TEWL) is managed by binding water in the SC for example or maximizing water circulation within the epidermis, ensuring an acidic pH on the skin or the secretion of anti-microbial peptides to counteract the colonization with opportunistic bacteria. A dysfunction of these functions of the skin is characteristic for multiple dermatologic conditions including psoriasis and atopic dermatitis.

[0014] Various physiological and / or pathological situations may result in a reduction in one or more of these functions of the skin. A prevalent situation is the situation in newborns and infants in which the physical, biochemical and / or microbiome barrier function of the skin is underdeveloped. Their stratum corneum is thinner and less cohesive, resulting in increased transepidermal water loss and heightened susceptibility to irritants and pathogens. Biochemically, infant skin pH is slightly more alkaline, the production of lipids and antimicrobial peptides is lower, compromising the skin's ability to maintain hydration and defend against microbial colonization. Additionally, the infant skin microbiome is still in the process of maturation, the composition of the skin microbiome changes over the course of the first year of life beginning with a rapid colonization after the newborn leaves the womb, making the skin more prone to early colonization by Staphylococcus aureus, which can affect immune responses and overall skin health. The development of the infantile skin barrier and its microbiome have been linked with skin diseases such as atopic dermatitis. In particular dysbiosis or the disruption of the balance of the infantile skin microbiome have been linked to atopic dermatitis and seborrheic dermatitis. Intervening to prevent dysbiosis of the newborn during the development of the skin may prevent development of skin diseases (Schoch JJ, Monir RL, Satcher KG, Harris J, Triplett E, Neu J. The infantile cutaneous microbiome: A review. Pediatr Dermatol. 2019;36:574-580. https : / / doi.org / 10.1111 / pde.13870).BYH240210 FC -3- The skin barrier is not considered fully mature at birth and continues to develop during the first year of life. Simultaneously, the immune system is also developing, notably through the crosstalk between the skin microbiome and other environmental factors. This period represents a critical window when the skin is particularly vulnerable to environmental stressors such as pollution and infections. Maintaining and strengthening the integrity of the infant skin barrier while promoting the growth of non-pathogenic bacteria is essential, as this serves as a protective measure against early skin barrier breakdown, which can lead to sensitization and improper immune system development, potentially resulting in the atopic march.

[0015] Many of such protective functions for the human fetus and newborn are carried out by the vernix caseosa, a complex membranous structure comprising about 80% water, 10% protein and 10% lipids. The vernix caseosa is generated on the skin of the fetus during the last trimester of gestation, which has a role in innate immunity potentially mediated by antimicrobial peptides comprised, the prevention of water loss and temperature regulation (Schoch JJ, Monir RL, Satcher KG, Harris J, Triplett E, Neu J. The infantile cutaneous microbiome: A review. Pediatr Dermatol. 2019;36:574-580. https : / / doi.org / 10.1111 / pde.13870). Natural vernix caseosa contains various types of lipids including cholesterol esters, ceramides, triglycerides cholesterol, free fatty acids, phospholipids wax esters, squalene, wax diesters, cerebrosides and cholesterol sulphate. The loss of the vernix caseosa soon after birth leaves the newborn skin prone to detrimental situation such as the colonization with opportunistic bacteria, inter alia as the pH of the skin of the newborn is uniformly neutral. The vernix caseosa has been implicated in the development of the acid mantle or the skin acidity that starts within the first 16 hours after birth, which is relevant to inhibit the growth of opportunistic and / or pathogenic bacteria and which may support the colonization with commensal bacterial (Schoch JJ, Monir RL, Satcher KG, Harris J, Triplett E, Neu J. The infantile cutaneous microbiome: A review. Pediatr Dermatol. 2019;36:574-580. https : / / doi.org / 10.1111 / pde.l3870). Further factors establishing the acid mantle are sebaceous glands, sweat glands and a balanced skin microbiome. Therefore, there is a need to provide means to support the skin functions in newborns, infants or children. In particular, there is a need for providing composition for use in newborns, infants or children which support all skin functions and are not detrimental, which are therefore devoid of potentially ingredients such as volatile siloxanes, parabens, sulfates or perfumes which may affect any one of the skin’s functions negatively. In a further aspect, the disclosure relates to compositions for mimicking the function of vernix caseosa to address in particular the need in newborns, infants or children to prevent the colonization of their skin with opportunistic or pathogenic bacteria, protect it from irritants and / or reduce transepidermal water loss. The vernixBYH240210 FC -4-caseosa supports the development of all three barrier functions of the skin in infants and thereby helps to reduce the onset of skin diseases such atopic dermatitis or atopic eczema in infants. Loss of skin function such as increased TEWL is associated with dry skin which has been found to precede the development of atopic dermatitis or atopic eczema in childhood. Reduced vernix caseosa was associated with skin dryness and higher TEWL values (Rehbinder et al. Predicting skin barrier dysfunction and atopic dermatitis in early infancy. J Allergy Clin Immunol Pract.

[0016] 2019. https: / / doi.Org / 10.1016 / j.jaip.2019.09.014).

[0017] The beneficial role of commensal Staphylococci for the host has been shown in infants. Significantly fewer commensal staphylococci were present at the age of 2 months in infants that went on to develop atopic dermatitis (AD) by the age of 12 months, compared to control subjects, suggesting commensal staphylococci have a protective role against the later development the skin disease AD. Furthermore, young infants did not have noticeably dysbiotic communities and were not colonized by S. aureus before having AD (Kennedy EA, Connolly J, Hourihane JO, Fallon PG, McLean WHI, Murray D, et al. Skin microbiome before development of atopic dermatitis: early colonization with commensal staphylococci at 2 months is associated with a lower risk of atopic dermatitis at 1 year. J Allergy Clin Immunol.

[0018] 2017;139(l): 166-72). Similarly, in a prospective birth cohort study of 149 infants, S. aureus was more prevalent at age 3 months on the skin of infants who later developed AD. S. aureus prevalence was increased at AD onset and within an average of 2 months before onset, when compared with age-matched, unaffected infants, suggesting that specific changes in early-life skin colonization predict clinical AD onset ((Meylan P, Lang C, Mermoud S, Johannsen A, Norrenberg S, Hohl D, et al. Skin colonization by Staphylococcus aureus precedes the clinical diagnosis of atopic dermatitis in infancy. J Invest Dermatol. 2017; 137(12):2497- 504.)).

[0019] Controlling the growth of S. aureus in the early life and in the meantime supporting the growth of commensal staphylococci, like S. epidermidis, could act as a protective measure to support healthy skin development and potentially reduces the risk of developing atopic eczema. However, there is a need to provide reliable means to selective support the growth and presence of commensal bacteria over pathogenic or opportunistic pathogenic bacteria and / or selectively reduce the growth of pathogenic and opportunistic pathogenic bacteria for the benefit of the (human) host.

[0020] S. epidermidis, has been recognized as the “microbial guardian of skin health”, S. epidermidis is a Gram-positive bacterium that is ubiquitous in the human skin and mucosal flora. As one of the earliest colonizers of the skin after birth, S. epidermidis plays an important role in cutaneousBYH240210 FC -5-immunity and maintaining microbial community homeostasis. The mechanism by which commensal microorganisms prevent or impede the colonization of the host with harmful bacteria has also been termed colonization resistance. Therefore, there is a need in the art to identify prebiotics that can selectively support the growth of commensal, host-beneficial bacteria over that of opportunistic pathogenic or pathogenic bacteria in the different microbiomes of the host.

[0021] Traditionally, while skin infections are treated with antibiotics, skin diseases that are inflammatory diseases such as atopic eczema are managed with anti-inflammatory products. However, recent discoveries indicate that the pathophysiology of these diseases involves significant microbiome alterations, suggesting that treatment should also address the dysbiosis observed in these conditions (Schoch JJ, Monir RL, Satcher KG, Harris J, Triplett E, Neu J. The infantile cutaneous microbiome: A review. Pediatr Dermatol. 2019;36:574-580. https : / / doi.org / 10.1111 / pde.l3870)). In atopic dermatitis, the skin barrier is compromised, making it more susceptible to colonization by Staphylococcus aureus, which can exacerbate inflammation and worsen symptoms. This overgrowth of S. aureus not only contributes to the severity of the condition but also disrupts the skin's microbiome balance. Therefore, effective management of atopic dermatitis should include strategies to restore the skin barrier and address the microbial imbalance, potentially reducing S. aureus colonization.

[0022] Therefore, considerable efforts have been undertaken to identify a more specific approach to supporting a situation of colonization resistance on the skin including the identification of prebiotics such as carbohydrates and fibers and methods to support the growth of commensals including the Alditol Xylitol in WO2021212073 or WO2021212077 or identify components including plant extracts that reduce the growth of (pathogenic) bacteria in the skin microbiome as disclosed in CN111407719. CN109303746 provides prebiotic compositions. CN111388403 discloses compositions comprising FLORASKIN L, OPTIMEALTH 10W, Aquaxyl™ and further ingredients. Aquaxyl™ is a composition which comprises the alditol Xylitol (CAS 87-99-9) at 5.0 to 15.0% (w / v), the dehydrated derivate of Xylitol Anhydroxyxylitol as 1,4-Anhydro-D-xylitol (CAS 53448-53-6) at 24.0 to 34.0% (w / v) and the alditol glucoside Xylitylglucoside (CAS 1095751-96-4) at 35.0 to 50.0% (w / v), Water (CAS 7732-18-5) at 15 to 17% (w / v) and Glucose (CAS 50-99-7) at 0 to 5% (w / v). As disclosed in CN111388403 Aquaxyl™ functions as a humectant and moisturizer to reduce trans epithelial water loss (TEWL) and manage water circulation and the water reservoir in the skin. Hence, a technical problem to be solved is providing a composition to support the development of skin barrierBYH240210 FC -6-functions and / or that prevents the breakdown of a barrier to improve the skin care of newborns and babies.

[0023] The barrier function of the skin and the protection the skin provides against external threats resulting from pathogenic microbes, toxins, ultraviolet radiation, chemical, oxidative stress, temperature, humidity and mechanical stress are ensured and supported by an ample supply of nutrients such as vitamins. Vitamins enhance the biochemical barrier function of the skin and support the production of lipids relevant for the skin. There is a need for providing a composition for use on the skin in particular for newborn and infant skin that support all barrier functions of the skin (physical, biochemical and microbial) preferably by synergistic effects of the ingredients of the composition by mimicking the function as well as the structure of the vemix caseosa. Hence, another technical problem to be solved is providing a composition that mimics the structure and / or function of the vemix caseosa given the importance of vernix caseosa mediated effects after the sudden exposure of the skin of newborns and infants to such external threats as microbes, toxins, ultraviolet radiation, chemical, oxidative stress, temperature, humidity and mechanical stress.

[0024] The present disclosure satisfies these and other needs.

[0025] SUMMARY

[0026] The present disclosure is based on the surprising finding that the addition of a selective prebiotic into compositions supports and / or stabilizes a host-beneficial microbiome at the site of the host where the composition has been applied. It has been found that combining a specific alditol with a specific alditol derivate of said alditol in a dehydrated state and with a specific alditol glucoside results in a selective prebiotic that can be used to selectively support the growth of beneficial bacteria (in particular S. epidermidis) in the microbiota and / or reduce the growth of pathogenic (in particular S. aureus) and opportunistic pathogenic bacteria in the microbiota. In particular the unexpected finding that a selective prebiotic comprising the alditol Xylitol, the dehydrated derivate of said alditol Anhydroxylitol, preferably 1,4-Anhydro-D-xylitol and the alditol glucoside of said alditol Xylitylglucoside can have that selective prebiotic effect, but also the finding that a composition consisting of these three ingredients or consisting of Xylitol, Anhydroxylitol, preferably 1,4-Anhydro-D-xylitol, Xylitylglucoside, Water and Glucose already can have such a selective prebiotic effect was unexpected.

[0027] It has been found that the beneficial effect of such a selective prebiotic can be well incorporated in leave-on topical compositions such as water in oil (W / O) emulsions, oil in water (O / W)BYH240210 FC -7-emulsions and rinse-off topical compositions such as washes that can have a beneficial effect on microbiomes in general and on skin microbiomes in particular in topical compositions for use on the skin that comprise a selective prebiotic, at least one humectant, at least one provitamin, vitamin and / or vitamin derivate selected from provitamin, vitamin B3 and / or a salt thereof, preferably niacinamide, provitamin, vitamin Bs and / or a salt thereof, preferably dexpanthenol and / or provitamin, vitamin E and / or a salt thereof, preferably tocopheryl acetate, and at least two lipids from the list comprising or consisting of ceramides, cholesterol, cholesterol esters, triglycerides, free fatty acids, free fatty acid derivates including glyceryl oleate and ethyl linoleate, caprylic capric triglyceride, Butyrospermum parkii (shea) butter, shea butter derivatives, squalane and / or squalene.

[0028] These lipids can be considered vemix caseosa like lipids. Said vernix caseosa like lipids can be lipids found in vernix caseosa and / or from lipids that are structurally or functionally similar to the lipids found in vernix caseosa. Without being bound by theory, the inventors believe that the inclusion of vemix caseosa like lipids can result in the formation of a vernix caseosa like lipid complex on the skin which can support in particular the physical barrier function of the skin. Preferably, the vernix caseosa-like lipids in topical compositions according to this disclosure are ceramide, cholesterol, free fatty acid, and squalene, or are a synthetic form of these lipids, such as ethyl linoleate and glyceryl oleate (similar to vernix caseosa free fatty acids), Butyrospermum parkii (shea) butter (similar to vernix caseosa cholesterol and triglycerides) including Butyrospermum parkii (shea) butter derivates such as shea butter glycereth-8-esters, caprylic / capric triglyceride (similar to vemix caseosa triglycerides), and squalane (similar to vemix caseosa squalene).

[0029] The selective prebiotic in the compositions according to this disclosure has a selective bacteriostatic and / or a selective growth supporting function.

[0030] It was surprisingly found that the addition of a selective prebiotic in particular when the selective prebiotic is a composition comprising or consisting of:

[0031] i. An alditol, namely Xylitol

[0032] ii. a dehydrated derivate of said alditol, namely Anhydroxylitol, preferably 1,4- Anhydro-D-xylitol and

[0033] iii. an alditol glucoside of said alditol, namely Xylitylglucoside,

[0034] to the topical compositions of this disclosure can provide for a composition that can simultaneously support all barrier functions of the skin. 0.01 to 8.00%, preferably 1.00 toBYH240210 FC -8- 6.00%, more preferably 1.00 to 3.00%, most preferably 1% or 3% of the selective prebiotic are comprised in the topical compositions according to this disclosure. Most preferably 1% or 3% of the selective prebiotic are comprised in the topical compositions and the composition of the selective prebiotic comprises

[0035] i. the alditol Xylitol,

[0036] ii. the dehydrated derivate of said alditol Anhydroxylitol, preferably 1,4-Anhydro-D- xylitol,

[0037] iii. the alditol glucoside of said alditol Xylitylglucoside,

[0038] An example of a preferred selective prebiotic, unexpectedly identified herein, is the composition sold under the name Aquaxyl™, which comprises the alditol Xylitol (CAS 87-99-9) at 5.0 to 15.0% (w / v), the dehydrated derivate of Xylitol Anhydroxyxylitol as 1,4-Anhydro-D-xylitol (CAS 53448-53-6) at 24.0 to 34.0% (w / v) and the alditol glucoside Xylitylglucoside (CAS 1095751-96-4) at 35.0 to 50.0% (w / v), Water (CAS 7732-18-5) at 15 to 17% (w / v) and Glucose (CAS 50-99-7) at 0 to 5% (w / v) of this selective prebiotic. In a preferred embodiment the selective prebiotic comprises or consists of:

[0039] i. 5.0 to 15.0% (w / v) Xylitol, preferably 10.0 to 12.0% (w / v) Xylitol,

[0040] ii. 24.0 to 34.0% (w / v) Anhydroxylitol, preferably 24.0 to 34.0% (w / v) 1,4- Anhydro-D-xylitol, more preferably 28.0 to 32.0% (w / v) Anhydroxylitol, most preferably 28.0 to 32.0% (w / v) 1,4-Anhydro-D-xylitol, and

[0041] iii. 35.0 to 50.0% (w / v) Xylitylglucoside, preferably 40.0 to 45.0% (w / v) Xylitylglucoside,

[0042] wherein the selective prebiotic has a selective bacteriostatic and / or a selective growth supporting function. Preferably, in this embodiment, the selective prebiotic supports the growth of beneficial bacteria Staphylococcus epidermidis and / or reduces the growth of pathogenic or opportunistic pathogenic bacteria Staphylococcus aureus and / or Cutibacterium acnes. and / or reduces the growth of commensal bacteria Corynebacterium striatum, preferably when beneficial bacteria are in growth competition with pathogenic and / or opportunistic pathogenic and / or commensal bacteria.

[0043] In another preferred embodiment the selective prebiotic comprises or consists of:

[0044] i. 5.0 to 15.0% (w / v) Xylitol, preferably 10.0 to 12.0% (w / v) Xylitol,BYH240210 FC -9- ii. 24.0 to 34.0% (w / v) Anhydroxylitol, preferably 24.0 to 34.0% (w / v) 1,4- Anhydro-D-xylitol, more preferably 28.0 to 32.0% (w / v) Anhydroxylitol, most preferably 28.0 to 32.0% (w / v) 1,4-Anhydro-D-xylitol,

[0045] iii. 35.0 to 50.0% (w / v) Xylitylglucoside, preferably 40.0 to 45.0% (w / v) Xylitylglucoside,

[0046] iv. 12 to 20% (w / v) Water, preferably 15 to 17% (w / v) Water, and

[0047] v. 0 to 5% (w / v) Glucose, preferably 1 to 4% (w / v) D-Glucose,

[0048] wherein the selective prebiotic has a selective bacteriostatic and / or a selective growth supporting function. Preferably, in this embodiment, the selective prebiotic supports the growth of beneficial bacteria Staphylococcus epidermidis and / or reduces the growth of pathogenic or opportunistic pathogenic bacteria Staphylococcus aureus and / or Cutibacterium acnes. and / or reduces the growth of commensal bacteria Corynebacterium striatum, preferably when beneficial bacteria are in growth competition with pathogenic and / or opportunistic pathogenic and / or commensal bacteria.

[0049] Surprisingly, the beneficial effect on microbiomes in general and on skin microbiomes in particular of the selective prebiotic disclosed herein can be well incorporated in leave-on compositions including (W / O) emulsions such as creams or (O / W) emulsions such as lotions and rinse-off topical compositions such as washes that can be:

[0050] A topical composition, preferably an emulsion or wash, more preferably a (W / O) emulsion, (O / W) emulsion or wash, for use on the skin comprising:

[0051] a. 0.01 to 8.00%, preferably 1.00 to 6.00%, more preferably 1.00 to 3.00%, most preferably 1% or 3% of a selective prebiotic comprising:

[0052] i. Xylitol,

[0053] ii. Anhydroxylitol, preferably as 1,4-Anhydro-D-xylitol, and iii. Xylitylglucoside,

[0054] b. at least one humectant,

[0055] c. at least one provitamin, vitamin and / or vitamin derivate from provitamin, vitamin B3 and / or a salt thereof, preferably niacinamide, provitamin, vitamin Bs and / or a salt thereof, preferably dexpanthenol and / or provitamin, vitamin E and / or a salt thereof, preferably tocopheryl acetate, and

[0056] d. at least two lipids from the list comprising or consisting of ceramides, cholesterol, cholesterol esters, triglycerides, free fatty acids, free fatty acidBYH240210 FC -10- derivates including glyceryl oleate and ethyl linoleate, caprylic capric triglyceride, Butyrospermum parkii (shea) butter, shea butter derivatives, squalane and / or squalene.

[0057] Unexpectedly, it has been found that the surprising selective prebiotic as detailed above can be incorporated in such topical compositions according to the disclosure which can support all three barrier functions or layers of the skin. Topical compositions according to this disclosure can have a synergistic effect to potentially simultaneously support the biochemical barrier, the microbial barrier and the physical barrier function of the skin

[0058] A solution to the technical problems of the prior art is therefore provided by compositions according to claim 1.

[0059] BRIEF DESCRIPTION OF THE FIGURES

[0060] Fig. 1 shows the results of Example 1. To be considered 'selective,' a test product or combination of test products should reduce the bacterial quantity of Staphylococcus aureus while increasing the bacterial quantity of Staphylococcus epidermidis. Selectivity is achieved when the two bar charts fall between the two values defined by the control. Test product A achieves a reduction of the bacterial load of Staphylococcus aureus by 23% while supporting the growth of Staphylococcus epidermidis by 18% compared to the control. In a competitive environment, test product A serves as a selective source of energy that is preferentially metabolized by Staphylococcus epidermidis. The specific strains of Staphylococcus aureus (ATCC® 6538™) and Staphylococcus epidermidis (ATCC® 14990™) used in this example are indicated.

[0061] Fig. 2 shows the results of Example 2. The specific strains of Staphylococcus aureus (ATCC® 6538™), Staphylococcus epidermidis (ATCC® 14990™), Corynebacterium striatum (ATCC® 6940™) and Cutibacterium acnes (ATCC® 6919™) used in this example are indicated.

[0062] Fig. 3 shows the results of Example 3. Both the chassis - Aquaxyl™ and the chassis -galactooligosaccharide treatment were cream compositions comprising glycerin, at least two vemix caseosa like lipids, and dexpanthenol together with either 3% (w / w) Aquaxyl™ or 0.75% (w / w) product C (a galactooligosaccharide).

[0063] Fig. 4 shows the quantification of the microbial load on the skin in IHUT treated infants and children after 28 days of treatment as measured by 16S rRNA qPCR.

[0064] Fig. 5 shows the results of diversity measurements of the skin microbiome based on 16S rRNA sequencing in IHUT treated infants and children after 28 days of treatment.BYH240210 FC -11- EMBODIMENTS

[0065] In an embodiment the compositions disclosed herein can be:

[0066] A topical composition, preferably an emulsion or wash, more preferably a (W / O) emulsion, an (O / W) emulsion or wash, for use on the skin comprising or consisting of:

[0067] a. 0.01 to 8.00%, preferably 1.00 to 6.00%, more preferably 1.00 to 3.00%, most preferably 1 to 3% of a selective prebiotic:

[0068] i. Xylitol,

[0069] ii. Anhydroxylitol, preferably 1,4-Anhydro-D-xylitol,

[0070] iii. Xylitylglucoside,

[0071] b. lactic acid, glycerin, pyrrolidone carboxylic acid, sodium pyrrolidone carboxylic acid, dexpanthenol, 1,2-hexanediol, 1,2-heptanediol and / or a composition comprising or consisting of saccharide isomerate, water, citric acid and sodium citrate,

[0072] c. at least one provitamin, vitamin and / or vitamin derivate from provitamin, vitamin B3 and / or a salt thereof, preferably niacinamide, provitamin, vitamin Bs and / or a salt thereof, preferably dexpanthenol and / or provitamin, vitamin E and / or a salt thereof, preferably tocopheryl acetate, and

[0073] d. at least two lipids from the list comprising or consisting of ceramides, cholesterol, cholesterol esters, triglycerides, free fatty acids, free fatty acid derivates including glyceryl oleate and ethyl linoleate, caprylic capric triglyceride, Butyrospermum parkii (shea) butter, shea butter derivatives, squalane and / or squalene.

[0074] In some embodiments the topical compositions according to this disclosure can comprise 0.01 to 8.00% (w / w), preferably 1.00 to 6.00% (w / w), more preferably 1.00 to 3.00% (w / w), most preferably 1% or 3% (w / w) of the selective prebiotic. In the more preferred embodiments the topical compositions according to this disclosure can comprise 1% or 3% (w / w) of the selective prebiotic.

[0075] In embodiments in which the topical composition according to this disclosure is a (W / O) emulsion, preferably a cream, an (O / W) emulsion, preferably a lotion, or a wash the topical compositions can comprise 0.01 to 8.00% (w / w), preferably 1.00 to 6.00% (w / w), more preferably 1.00 to 3.00% (w / w), most preferably 1% or 3% (w / w) of the selective prebiotic.BYH240210 FC -12- In embodiments of semisolid dosage forms of the topical compositions according to this disclosure the topical compositions can comprise 0.01 to 8.00% (w / w), preferably 1.00 to 6.00% (w / w), more preferably 1.00 to 3.00% (w / w), most preferably 1% or 3% (w / w) of the selective prebiotic.

[0076] In preferred embodiments, the topical compositions according to this disclosure can comprise 1% or 3% (w / w) of the selective prebiotic, more preferably the selective prebiotic is 1% or 3% (w / w) of the topical composition in these embodiments.

[0077] In some embodiments the topical compositions according to this disclosure can comprise 0.01 to 8.00% (w / v), preferably 1.00 to 6.00% (w / v), more preferably 1.00 to 3.00% (w / v), most preferably 1% or 3% (w / v) of the selective prebiotic. In the more preferred embodiments the topical compositions according to this disclosure can comprise 1% or 3% (w / v) of the selective prebiotic.

[0078] In embodiments in which the topical composition according to this disclosure is a solution, a suspension or an (O / W) emulsion, preferably a lotion, the topical compositions can comprise 0.01 to 8.00% (w / v), preferably 1.00 to 6.00% (w / v), more preferably 1.00 to 3.00% (w / v), most preferably 1% or 3% (w / v) of the selective prebiotic.

[0079] In embodiments of liquid dosage forms of the topical compositions according to this disclosure the topical compositions can comprise 0.01 to 8.00% (w / v), preferably 1.00 to 6.00% (w / v), more preferably 1.00 to 3.00% (w / v), most preferably 1% or 3% (w / v) of the selective prebiotic. In preferred embodiments, the topical compositions according to this disclosure can comprise 1% or 3% (w / v) of the selective prebiotic, more preferably the selective prebiotic is 1% or 3% (w / v) of the topical composition in these embodiments.

[0080] In any of these embodiments the composition comprising or consisting of saccharide isomer, water, citric acid and sodium citrate can be the composition commercially available under the name Pentavitin™. In this embodiment the support of all barrier functions can be simultaneous and / or synergistic.

[0081] In a more preferred embodiment, the topical composition can be a wash and can comprise or consists of at least one humectant from glycerin, 1,2-hexanediol, 1,2-heptanediol, dexpanthenol and / or a composition comprising or consisting of saccharide isomerate, water, citric acid and sodium citrate.

[0082] In another more preferred embodiment, the topical composition can be an (O / W) emulsion, most preferred a lotion, and can comprise or consisting of at least one humectant from glycerin,BYH240210 FC -13- 1,2-hexanediol, 1,2-heptanediol, dexpanthenol, sodium pyrrolidone carboxylic acid, and / or pyrrolidone carboxylic acid.

[0083] In another more preferred embodiment, the topical composition can be a (W / O) emulsion, most preferred a cream, and can comprise or consists of at least one humectant from glycerin, lactic acid, 1,2-hexanediol, 1,2-heptanediol, dexpanthenol, sodium pyrrolidone carboxylic acid, and / or pyrrolidone carboxylic acid.

[0084] In a preferred embodiment the compositions disclosed herein can be:

[0085] A topical composition, preferably an emulsion or wash, more preferably a (W / O) emulsion, an (O / W) emulsion or wash, for use on the skin comprising or consisting of:

[0086] a. 0.01 to 8.00%, preferably 1.00 to 6.00%, more preferably 1.00 to 3.00%, most preferably 1 to 3% of a selective prebiotic consisting of:

[0087] i. Xylitol,

[0088] ii. Anhydroxylitol, preferably 1,4-Anhydro-D-xylitol,

[0089] iii. Xylitylglucoside,

[0090] iv. Water, and

[0091] v. Glucose, preferably D-Glucose.

[0092] b. lactic acid, glycerin, pyrrolidone carboxylic acid, sodium pyrrolidone carboxylic acid, dexpanthenol, 1,2-hexanediol, 1,2-heptanediol and / or a composition comprising or consisting of saccharide isomerate, water, citric acid and sodium citrate,

[0093] c. at least one provitamin, vitamin and / or vitamin derivate from provitamin, vitamin B3 and / or a salt thereof, preferably niacinamide, provitamin, vitamin Bs and / or a salt thereof, preferably dexpanthenol and / or provitamin, vitamin E and / or a salt thereof, preferably tocopheryl acetate, and

[0094] d. at least two lipids from the list comprising or consisting of ceramides, cholesterol, cholesterol esters, triglycerides, free fatty acids, free fatty acid derivates including glyceryl oleate and ethyl linoleate, caprylic capric triglyceride, Butyrospermum parkii (shea) butter, shea butter derivatives, squalane and / or squalene.

[0095] In this embodiment the composition comprising or consisting of saccharide isomer, water, citric acid and sodium citrate can be the composition commercially available under the name Pentavitin™. In this embodiment the support of all barrier functions can be simultaneous and / or synergistic.BYH240210 FC -14- In a more preferred embodiment, the topical composition can be a wash and can comprise or consist of at least one humectant from glycerin, 1,2-hexanediol, 1,2-heptanediol, dexpanthenol and / or a composition comprising or consisting of saccharide isomerate, water, citric acid and sodium citrate.

[0096] In a more preferred embodiment, the topical composition can be an (O / W) emulsion, most preferred a lotion, and can comprise or consisting of at least one humectant from glycerin, 1,2-hexanediol, 1,2-heptanediol, dexpanthenol, sodium pyrrolidone carboxylic acid, and / or pyrrolidone carboxylic acid.

[0097] In another more preferred embodiment, the topical composition can be a (W / O) emulsion, most preferred a cream, and can comprise or consisting of at least one humectant from glycerin, lactic acid, 1,2-hexanediol, 1,2-heptanediol, dexpanthenol, sodium pyrrolidone carboxylic acid, and / or pyrrolidone carboxylic acid.

[0098] In an embodiment of the compositions as disclosed herein, the selective prebiotic can also be the humectant. In a preferred embodiment, the selective prebiotic and the humectant can be Aquaxyl™.

[0099] In another preferred embodiment of the compositions according to the disclosure the at least one humectant is dexpanthenol which can also be the at least one provitamin, vitamin and / or vitamin derivate. In an even more preferred embodiment of the disclosure two humectants are, Aquaxyl™. which can also be the selective prebiotic and dexpanthenol, which can also be the at least one provitamin, vitamin and / or vitamin derivate of the composition.

[0100] Compositions according to the disclosure can comprise at least one humectant, preferably lactic acid, glycerin, pyrrolidone carboxylic acid, sodium pyrrolidone carboxylic acid, dexpanthenol, 1,2-hexanediol, 1,2-heptanediol and a composition comprising or consisting of saccharide isomerate, water, citric acid and sodium citrate. Compositions according to the disclosure can preferably comprise lactic acid, glycerin, pyrrolidone carboxylic acid, sodium pyrrolidone carboxylic acid, 1,2-hexanediol and / or 1,2-heptanediol as the at least one humectant.

[0101] The careful selection of humectants in these more preferred embodiments results in an improved biochemical barrier function and overall in topical composition capable of providing optimized support for all three barrier functions.

[0102] In embodiments of the disclosure the selective prebiotic can comprise or consisting of i. 5.0 to 15.0% (w / v) Xylitol, preferably 10.0 to 12.0% (w / v) Xylitol, ii. 24.0 to 34.0% (w / v), Anhydroxylitol, preferably 1,4-Anhydro-D-Xylitol preferably 28.0 to 32.0% (w / v)BYH240210 FC -15- Anhydroxylitol, preferably 1,4-Anhydro-D-Xylitol, and iii. 35.0 to 50.0% (w / v) Xylitylglucoside, preferably 40.0 to 45.0% (w / v) Xylitylglucoside.

[0103] In a preferred embodiment of compositions according to the disclosure the at least two lipids in topical composition embodiments according to this disclosure can be at least two vemix caseosa like lipids from the list comprising Butyrospermum parkii (shea) butter, squalane, caprylic capric triglyceride, ceramides, ethyl linoleate, and / or cholesterols.

[0104] In another preferred embodiment of compositions according to the disclosure the composition is in the form of an emulsion, preferably a cream, and the at least two lipids can be at least two vemix caseosa like lipids from the list comprising Butyrospermum parkii (shea) butter, squalane, caprylic capric triglyceride, ceramides, ethyl linoleate, and / or cholesterols.

[0105] In another preferred embodiment of compositions according to the disclosure the composition is in the form of an emulsion, preferably a lotion, and the at least two lipids in the emulsion can be at least two vemix caseosa like lipids from the list comprising Butyrospermum parkii (shea) butter, squalane, caprylic capric triglyceride, ceramides, ethyl linoleate, and / or cholesterols. In another preferred embodiment of compositions according to the disclosure the composition is in the form of an emulsion, preferably a cream, and the at least two lipids can be at least two vemix caseosa like lipids from the list comprising Butyrospermum parkii (shea) butter, ethyl linoleate, and caprylic capric triglyceride, squalane and / or ceramides.

[0106] In another preferred embodiment of compositions according to this disclosure composition is in the form of a wash and the at least two lipids can be at least two vernix caseosa like lipids from the list comprising glyceryl oleate and / or a Butyrospermum parkii (shea) butter derivate, preferably shea butter glycereth-8-esters.

[0107] In an even more preferred embodiment of compositions according to the disclosure the composition is in the form of a (W / O) emulsion, preferably a cream, and the at least two lipids can be at least two vemix caseosa like lipids from the list comprising Butyrospermum parkii (shea) butter, squalane, caprylic capric triglyceride, ethyl linoleate, cholesterols and / or ceramides.

[0108] In embodiments the at least one provitamin, vitamin and / or vitamin derivate from provitamin, vitamin B3 and / or a salt thereof, preferably niacinamide, provitamin, vitamin Bs and / or a salt thereof, preferably dexpanthenol and / or provitamin, vitamin E and / or a salt thereof, preferably tocopheryl acetate, can act together to support the barrier functions of the skin. Preferably the topical compositions comprise niacinamide dexpanthenol and tocopheryl acetate. In theseBYH240210 FC -16-embodiments the ingredients can act together to simultaneously support the hydration and humectancy, to reinforce biochemical barrier function and epidermal homeostasis and / or contribute to protective and stabilizing effects within a lipid-rich formulation.

[0109] In embodiments of the disclosure the topical composition can have a pH from 3.8 to 5.5, preferably a pH from 3.8 to 4.5, 4.0 to 5.0, 4.4 to 5.5, 4.5 to 5.5 or 5.0 to 5.5, more preferably a pH from 4.0 to 5.5, most preferably a pH from pH 4.5 to pH 4.7, pH 4.5 to pH 5.5 or pH 4.4 to pH 5.5.

[0110] In preferred embodiments of compositions according to the disclosure as disclosed herein the pH of the composition is acidic, i.e. the pH is below 7, preferably the pH of the composition is pH 3.8 to 5.5, more preferably pH 3.8 to 4.5, 4.0 to 5.0, 4.4 to 5.5, 4.5 to 5.5 or 5.0 to 5.5, even more preferably pH 4.0 to 5.5, pH 4.4 to 5.5 or pH 4.5 to 5.5, most preferably pH 4.5 to pH 4.7. Having the pH of the compositions according to the disclosure as pH 3.8 to 4.5 may be preferred for compositions for use on vaginal skin. Having the pH of the compositions according to the disclosure herein as pH 4.0 to 5.5, in particular pH 4.5 to pH 4.7 may be preferred for compositions on the skin of newborns, infants and / or children. Having the pH of the compositions according to the disclosure as pH 5.0 to 5.5 may be preferred for compositions suitable for maintaining the pH of the skin.

[0111] In a more preferred embodiment, the topical composition can be a wash and can comprise or consist of at least one humectant from glycerin, 1,2-hexanediol, 1,2-heptanediol, dexpanthenol and / or a composition comprising or consisting of saccharide isomerate, water, citric acid and sodium citrate and can have a pH from pH 3.8 to 5.5, preferably pH 4.5 to pH 5.5.

[0112] In another more preferred embodiment, the topical composition can be an (O / W) emulsion, most preferred a lotion, and can comprise or consist of at least one humectant from glycerin, 1,2-hexanediol, 1,2-heptanediol, dexpanthenol, sodium pyrrolidone carboxylic acid, and / or pyrrolidone carboxylic acid and can have a pH from pH 3.8 to 5.5, preferably pH 4.4 to pH 5.5. In another more preferred embodiment, the topical composition can be a (W / O) emulsion, most preferred a cream, and can comprise or consist of at least one humectant from glycerin, lactic acid, 1,2-hexanediol, 1,2-heptanediol, dexpanthenol, sodium pyrrolidone carboxylic acid, and / or pyrrolidone carboxylic acid and can have a pH from pH 3.8 to 5.5, preferably pH 3.8 to pH 4.5, pH 4.0 to 5.0 or pH 5.0 to 5.5, more preferably pH 4.5 to 4.7.

[0113] In a more preferred embodiment, the topical composition can be a wash and can comprise or consist of at least one humectant from glycerin, 1,2-hexanediol, 1,2-heptanediol, dexpanthenolBYH240210 FC -17-and / or a composition comprising or consisting of saccharide isomerate, water, citric acid and sodium citrate, the at least two lipids can be at least two vernix caseosa like lipids from the list comprising glyceryl oleate and a Butyrospermum parkii (shea) butter derivate, preferably shea butter glycereth-8-esters and can have a pH from pH 3.8 to 5.5, preferably pH 4.5 to pH 5.5. In another more preferred embodiment, the topical composition can be an (O / W) emulsion, most preferred a lotion, and can comprise or consist of at least one humectant from glycerin, 1,2-hexanediol, 1,2-heptanediol, dexpanthenol, sodium pyrrolidone carboxylic acid, and / or pyrrolidone carboxylic acid, the at least two lipids can be at least two vernix caseosa like lipids from the list comprising Butyrospermum parkii (shea) butter, squalane, caprylic capric triglyceride, ceramides, ethyl linoleate, and / or cholesterols and can have a pH from pH 3.8 to 5.5, preferably pH 4.4 to pH 5.5.

[0114] In another more preferred embodiment, the topical composition can be a (W / O) emulsion, most preferred a cream, and can comprise or consist of at least one humectant from glycerin, lactic acid, 1,2-hexanediol, 1,2-heptanediol, dexpanthenol, sodium pyrrolidone carboxylic acid, and / or pyrrolidone carboxylic acid, the at least two lipids can be at least two vernix caseosa like lipids from the list comprising Butyrospermum parkii (shea) butter, squalane, caprylic capric triglyceride, ethyl linoleate and / or ceramides, and can have a pH from pH 3.8 to 5.5, preferably pH 3.8 to pH 4.5, pH 4.0 to 5.0 or pH 5.0 to 5.5, more preferably pH 4.5 to 4.7.

[0115] The pH selection based on galenic form wash, (O / W) emulsion or (W / O) emulsion has shown the best for maintaining and supporting barrier integrity and / or skin microbiome.

[0116] Disclosed herein are compositions comprising selective prebiotics and uses of selective prebiotics. Preferably the compositions disclosed have an acidic pH, preferably pH 3.8 to 5.5, more preferably pH 4.0 to 5.5, most preferably pH 4.4 to 5.5, pH 4.5 to pH 5.5 or pH 4.5 to pH 4.7, to mimic the function of the vernix caseosa in the establishment of the acid mantle to aid in selectively inhibiting the growth of opportunistic and / or pathogenic bacteria on the skin. Disclosed herein are topical compositions comprising at least one selective prebiotic, at least one humectant, at least one provitamin, vitamin and / or vitamin derivate from vitamin B3 and / or a salt thereof, preferably niacinamide, vitamin B5 and / or a salt thereof, preferably dexpanthenol and / or vitamin E and / or a salt thereof, preferably tocopheryl acetate, and at least two lipids deemed vernix caseosa like, wherein the selective prebiotic has a selective bacteriostatic and / or a selective growth supporting function.BYH240210 FC -18- Vemix like lipids that can be included in the topical compositions according to the disclosure to improve the skin supportive effects as disclosed herein comprise glyceryl oleate, ethyl linoleate, ceramides, Butyrospermum parkii (shea) butter and shea butter derivatives, squalane, and caprylic / capric triglyceride to replenish the skin with various types of lipids that strengthen the physical barrier. The humectants in the topical compositions lactic acid, glycerin, pyrrolidone carboxylic acid, sodium pyrrolidone carboxylic acid, dexpanthenol, 1,2-hexanediol, 1,2-heptanediol and / or a composition comprising or consisting of saccharide isomerate, water, citric acid and sodium citrate can be added to enhance skin hydration and promote skin homeostasis. This comprehensive additional support promotes healthy skin development during infancy in newborns, infants and children. Preferably the compositions according to the disclosure disclosed have an acidic pH, preferably pH 3.8 to 4.5, 4.0 to 5.0, 4.4 to 5.5, 4.5 to 5.5 or 5.0 to 5.5, more preferably a pH from 4.0 to 5.5, most preferably a pH from pH 4.5 to pH 4.7, pH 4.5 to pH 5.5 or pH 4.4 to pH 5.5.

[0117] In an embodiment the selective prebiotic can be a commercially available compositions including Aquaxyl™ which comprises the alditol Xylitol, the Xylitol derivate Anhydroxyxylitol, preferably 1,4-Anhydro-D-xylitol, and the Xylitol glucoside Xylitylglucoside in a ratio of Xylitol at 1 to Anhydroxylitol, preferably 1,4-Anhydro-D-xylitol, at 1.6 to 6.8, preferably at 1.6 to 4.8, more preferably at 1.666 - 2.333, most preferably at 2.333 to Xylitolglucoside at 2.33 to 10, preferably at 2.333 to 7, more preferably at 2.333 - 3.333, most preferably at 3.333. In according embodiments the selective prebiotic is preferably in a ratio of Xylitol at 1 to 1,4-Anhydro-D-xylitol at 2.333 to Xylitylglucoside at 3.333. Preferably the compositions in these embodiments have an acidic pH, more preferably pH 3.8 to 4.5, 4.0 to 5.0, 4.4 to 5.5, 4.5 to 5.5 or 5.0 to 5.5, even more preferably a pH from 4.0 to 5.5, most preferably a pH from pH 4.5 to pH 4.7, pH 4.5 to pH 5.5 or pH 4.4 to pH 5.5.

[0118] In a preferred embodiment, the topical composition is a (W / O) emulsion, preferably a cream, and the selective prebiotic is at 0.01 to 8.00% (w / w), preferably at 1.00 to 6.00% (w / w), more preferably at 1% (w / w) or 3% (w / w) of the topical composition and the selective prebiotic comprises or consists of i. Xylitol at 5.0 to 15.0% (w / v), preferably 10.0 to 12.0% (w / v) of the selective prebiotic, ii. Anhydroxylitol, preferably 1,4-Anhydro-D-xylitol at 24.0 to 34.0% (w / v), preferably at 28.0 to 32.0% (w / v) of the selective prebiotic, and iii. Xylitylglucoside, at 35.0 to 50.0% (w / v), preferably at 40.0 to 45.0% (w / v) of that selective prebiotic, the at least one humectant is dexpanthenol, sodium pyrrolidone carboxylic acid, pyrrolidone carboxylic acid, glycerin, lactic acid, 1,2-hexanediol and / or 1,2-heptanediol and the at least one provitamin, vitamin and / or vitamin derivate is dexpanthenol, niacinamide and / or tocopherylBYH240210 FC -19-acetate and the at least two lipids are ceramides, caprylic capric triglyceride, ethyl linoleate, Butyrospermum parkii (shea) butter and / or squalane and the pH of the composition is pH 4.5 to pH 4.7. In this embodiment the support of all barrier functions can be simultaneous and / or synergistic.

[0119] In another preferred embodiment, the topical composition is a (O / W) emulsion, preferably a lotion, and the selective prebiotic is at 0.01 to 8.00% (w / w), preferably at 1.00 to 6.00% (w / w), more preferably at 1% (w / w) or 3% (w / w) of the topical composition and the selective prebiotic comprises or consists of i. Xylitol at 5.0 to 15.0% (w / v), preferably 10.0 to 12.0% (w / v) of the selective prebiotic, ii. Anhydroxylitol, preferably 1,4-Anhydro-D-xylitol at 24.0 to 34.0% (w / v), preferably at 28.0 to 32.0% (w / v) of the selective prebiotic, and iii. Xylitylglucoside, at 35.0 to 50.0% (w / v), preferably at 40.0 to 45.0% (w / v) of that selective prebiotic, the at least one humectant is glycerin, 1,2-hexanediol, 1,2-heptanediol, dexpanthenol, sodium pyrrolidone carboxylic acid, and / or pyrrolidone carboxylic acid and the at least one provitamin, vitamin and / or vitamin derivate is dexpanthenol, niacinamide and / or tocopheryl acetate and the at least two lipids are Butyrospermum parkii (shea) butter, squalane, caprylic capric triglyceride, ceramides, ethyl linoleate, and / or cholesterols and the pH of the composition is pH 4.4 to pH 5.5. In this embodiment the support of all barrier functions can be simultaneous and / or synergistic.

[0120] In another preferred embodiment, the topical composition is a wash and the selective prebiotic is at 0.01 to 8.00% (w / w), preferably at 1.00 to 6.00% (w / w), more preferably at 1% (w / w) or 3% (w / w) of the topical composition and the selective prebiotic comprises or consists of i. Xylitol at 5.0 to 15.0% (w / v), preferably 10.0 to 12.0% (w / v) of the selective prebiotic, ii. Anhydroxylitol, preferably 1,4-Anhydro-D-xylitol at 24.0 to 34.0% (w / v), preferably at 28.0 to 32.0% (w / v) of the selective prebiotic, and iii. Xylitylglucoside, at 35.0 to 50.0% (w / v), preferably at 40.0 to 45.0% (w / v) of that selective prebiotic, the at least one humectant is glycerin, 1,2-hexanediol, 1,2-heptanediol, dexpanthenol and / or a composition comprising or consisting of saccharide isomerate, water, citric acid and sodium citrate and the at least one provitamin, vitamin and / or vitamin derivate is dexpanthenol, niacinamide and / or tocopheryl acetate and the at least two glyceryl oleate and a Butyrospermum parkii (shea) butter derivate, preferably shea butter glycereth-8-esters and the pH of the composition is pH 4.5 to pH 5.5. In this embodiment the support of all barrier functions can be simultaneous and / or synergistic. In an even more preferred embodiment, the selective prebiotic is the commercially available Aquaxyl™, preferably at 1% or 3% (w / v) or (w / w) of Aquaxyl™ of the topical composition,BYH240210 FC -20-the at least one humectant is dexpanthenol and Aquaxyl™, the at least one provitamin, vitamin and / or vitamin derivate is dexpanthenol and niacinamide, and the at least two lipids are ceramide, caprylic capric triglyceride, Butyrospermum parkii (shea) butter ethyl linoleate and / or squalane the pH of the composition is pH 4.5 to pH 4.7. In this embodiment the support of all barrier functions can be simultaneous and / or synergistic.

[0121] In embodiments of the disclosure the topical compositions can be free of strong detergents, preferably free of sodium lauryl sulfate and sodium laureth sulfates, free of volatile siloxanes, preferably free of octamethylcyclotetrasiloxane (D4), decamethylcyclopentasiloxane (D5) and dodecamethylcyclohexasiloxane (D6), and / or free of preservatives, preferably free of parabens, methylisothiazolinone and / or mineral oils.

[0122] In certain preferred embodiments, the topical composition can be formulated to be particularly mild and compatible with sensitive or compromised skin, including infant or eczema-prone skin, to further support the use of selective prebiotics on sensitive or compromised skin. Accordingly, the composition is preferably free of strong detergents, such as anionic surfactants including sodium lauryl sulfate and sodium laureth sulfate, in order to avoid excessive removal of skin lipids and to preserve the integrity of the skin barrier. In addition, the composition is preferably free of volatile siloxanes, such as octamethylcyclotetrasiloxane (D4), decamethylcyclopentasiloxane (D5) and dodecamethylcyclohexasiloxane (D6), thereby favoring formulations that rely on non-volatile emollients and lipid components that are more consistent with the intended skin barrier-supporting function of the composition. Furthermore, the composition is preferably free of preservatives such as parabens and methylisothiazolinone, and / or free of mineral oils, in order to provide a formulation concept focused on simplicity, high tolerability and / or suitability for long-term or daily use on sensitive skin, while maintaining the desired cosmetic or dermatological performance of the composition.

[0123] In an embodiment the topical compositions according to this disclosure can be for use in the treatment and / or prevention of a skin disease, preferably for use in the treatment and / or prevention of an acne and / or an eczema skin disease, more preferably for use in the treatment and / or prevention of atopic dermatitis, contact dermatitis, dyshidrotic eczema and / or nummular eczema, most preferably for use in the treatment and / or prevention of atopic dermatitis, contact dermatitis, dyshidrotic eczema and / or nummular eczema in newborns, infants and / or children. The excellent mimicking of the protective and supporting functions of the vernix caseosa like complexes formed on the skin when the topical compositions according to the disclosure are applied to the skin in combination with the unexpected maintenance of the selective prebioticBYH240210 FC -21-function of the selective prebiotic comprised in the topical compositions render the disclosed topical compositions particularly well suited to support the prevention of dysbiosis observed with an onset of eczema skin disease or acne.

[0124] The topical compositions disclosed herein may be particularly well suited for use in the prevention of acne and / or eczema development in newborns, infants and / or children due to its formulation concept, which is designed to support the physiological development and maintenance of the skin barrier during early life. Newborn and infant skin is characterized by an immature physical barrier, an evolving biochemical lipid composition, and a developing skin microbiome, rendering it more susceptible to barrier dysfunction, inflammation and dysbiosis. The disclosed topical compositions comprise a combination of humectants, barrier-supporting lipids inspired by vernix caseosa, and a selective prebiotic, which together may contribute to maintaining skin hydration, reinforcing the lipid matrix of the stratum comeum, and supporting a balanced skin microbiome. By promoting a well-hydrated and structurally supported skin barrier and by providing conditions that are compatible with beneficial commensal microorganisms, the composition may reduce factors known to contribute to the initiation or exacerbation of inflammatory skin conditions, including acne and eczema. In particular the mild formulation approach, combined with suitability for daily and long-term use on sensitive skin, makes the topical compositions disclosed particularly appropriate for skin-disease preventive use in newborns, infants and children.

[0125] In another preferred embodiment, the disclosed compositions can be:

[0126] A topical composition for use in the treatment and / or prevention of a skin disease, from an acne and / or an eczema skin disease, preferred an eczema skin disease are atopic dermatitis, contact dermatitis, dyshidrotic eczema and / or nummular eczema, preferably in newborns, infants and / or children, preferably an emulsion or wash, more preferably a (W / O) emulsion or wash, even more preferably a (W / O) emulsion or wash of pH 3.8 - 5.5, most preferably a (W / O) emulsion or wash of 3.8 to 4.5, 4.0 to 5.0 or 5.0 to 5.5, for use on the skin comprising or consisting of:

[0127] a. 1.00 to 6.00%, preferably 1.00 to 3.00%, more preferably 1 or 3% of a selective prebiotic comprising or consisting of:

[0128] i. 10.0 to 12.0% (w / v) Xylitol,

[0129] ii. 28.0 to 32.0% (w / v) Anhydroxylitol, preferably 28.0 to 32.0% (w / v) 1,4-Anhydro-D-xylitol,

[0130] iii. 40.0 to 45.0% (w / v) Xylitylglucoside,BYH240210 FC -22- iv. 12 to 20% (w / v) Water, preferably 15 to 17% (w / v) Water, and v. 0 to 5% (w / v) Glucose, preferably 1 to 4 % (w / v) D-Glucose, b. lactic acid, glycerin, sodium pyrrolidone carboxylic acid, panthenol, and / or citric acid,

[0131] c. at least one provitamin, vitamin and / or vitamin derivate from provitamin, vitamin B3 and / or a salt thereof, preferably niacinamide, provitamin, vitamin Bs and / or a salt thereof, preferably dexpanthenol and / or provitamin, vitamin E and / or a salt thereof, preferably tocopheryl acetate, and

[0132] d. ceramides, cholesterol, cholesterol esters, triglycerides, free fatty acids, free fatty acid derivates including glyceryl oleate and ethyl linoleate, caprylic capric triglyceride, Butyrospermum parkii (shea) butter, shea butter derivatives, squalane and / or squalene.

[0133] In another preferred embodiment, the disclosed compositions can be:

[0134] A topical composition for use in the treatment and / or prevention of a skin disease, from an acne and / or an eczema skin disease, preferred an eczema skin disease are atopic dermatitis, contact dermatitis, dyshidrotic eczema and / or nummular eczema, preferably in newborns, infants and / or children, preferably an emulsion or wash, more preferably a (W / O) emulsion or wash, even more preferably a (W / O) emulsion or wash of pH 3.8 - 5.5, most preferably a (W / O) emulsion or wash of 3.8 to 4.5, 4.0 to 5.0 or 5.0 to 5.5, for use on the skin comprising or consisting of:

[0135] a. 1.00 to 6.00%, preferably 1.00 to 3.00%, more preferably 1 or 3% of a selective prebiotic comprising or consisting of:

[0136] i. 10.0 to 12.0% (w / v) Xylitol,

[0137] ii. 28.0 to 32.0% (w / v) Anhydroxylitol, preferably 28.0 to 32.0% (w / v) 1,4-Anhydro-D-xylitol,

[0138] iii. 40.0 to 45.0% (w / v) Xylitylglucoside,

[0139] iv. 12 to 20% (w / v) Water, preferably 15 to 17% (w / v) Water, and v. 0 to 5% (w / v) Glucose, preferably 1 to 4 % (w / v) D-Glucose, b. lactic acid, glycerin, sodium pyrrolidone carboxylic acid, panthenol, and / or citric acid,

[0140] c. niacinamide, dexpanthenol and / or tocopheryl acetate, and

[0141] d. ceramides, cholesterol, cholesterol esters, triglycerides, free fatty acids, free fatty acid derivates including glyceryl oleate and ethyl linoleate, caprylic capricBYH240210 FC -23- triglyceride, Butyrospermum parkii (shea) butter, shea butter derivatives, squalane and / or squalene.

[0142] In embodiments the compositions may also be used for non-therapeutic or cosmetic purposes in particular for strengthening the physical, biochemical and microbial layer of the skin, wherein the skin is newborn, infant, child, adolescent, adult or mature, preferably newborn and / or infant skin.

[0143] An essential unexpected observation by the inventors was that a selective prebiotic comprising the specific alditol Xylitol, the specific dehydrated derivate of said alditol Anhydroxylitol, preferably 1,4-Anhydro-D-xylitol and the specific alditol glucoside of said alditol Xylitylglucoside can have that selective prebiotic effect, but also the finding that a composition consisting of these three ingredients or consisting of Xylitol, Anhydroxylitol, preferably 1,4-Anhydro-D-xylitol, Xylitylglucoside, water and glucose already can have such a selective prebiotic effect, i.e. a selective bacteriostatic and / or selective prebiotic function.

[0144] In an embodiment, the selective prebiotic effect can support the growth of beneficial bacteria Staphylococcus epidermidis and / or reduces the growth of pathogenic or opportunistic pathogenic bacteria Staphylococcus aureus and / or Cutibacterium acnes. and / or reduces the growth of commensal bacteria Corynebacterium striatum, preferably when beneficial bacteria are in growth competition with pathogenic and / or opportunistic pathogenic and / or commensal bacteria.

[0145] In preferred embodiments, the selective bacteriostatic and / or selective prebiotic function is provided by a selective prebiotic comprising Xylitol, Anhydroxylitol, preferably 1,4-Anhydro-D-xylitol, Xylitylglucoside as the sole alditol-based carbohydrate system. In these embodiments the topical compositions and / or the compositions of the selective prebiotic are free of additional alditols.

[0146] In particularly preferred embodiments the selective bacteriostatic and / or selective prebiotic function can be provided by a selective prebiotic comprising or consisting of:

[0147] i. 5.0 to 15.0% (w / v) Xylitol, preferably 10.0 to 12.0% (w / v) Xylitol,

[0148] ii. 24.0 to 34.0% (w / v) Anhydroxylitol, preferably 24.0 to 34.0% (w / v) 1,4- Anhydro-D-xylitol, more preferably 28.0 to 32.0% (w / v) Anhydroxylitol, most preferably 28.0 to 32.0% (w / v) 1,4-Anhydro-D-xylitol,

[0149] iii. 35.0 to 50.0% (w / v) Xylitylglucoside, preferably 40.0 to 45.0% (w / v) Xylitylglucoside,BYH240210 FC -24- iv. 12 to 20% (w / v) Water, preferably 15 to 17% (w / v) Water, and

[0150] v. 0 to 5% (w / v) Glucose, preferably 1 to 4% (w / v) D-Glucose.

[0151] In embodiments commercially available compositions, for instance available under the name Aquaxyl™, can provide the selective bacteriostatic and / or selective prebiotic function. The inventors found that these selective prebiotic without additional alditol provide a defined and functionally balanced combination of Xylitol, Anhydroxylitol and Xylitylglucoside, which together may provide sufficient carbohydrate availability to interact with the skin microbiome while maintaining high formulation tolerability. In embodiments without additional alditols or free of additional alditols the microbiome modulating function can be provided without introducing additional alditols that could alter osmotic balance, broaden microbial accessibility in a non-selective manner, or dilute the specificity of the observed microbiome-supporting effect.

[0152] In an embodiment the selective prebiotic disclosed can be used on different microbiomes for achieving the selective bacteriostatic and / or selective prebiotic function, preferably the selective prebiotic disclosed can be used on epithelial-associated microbiomes with similar physiological constraints like the skin including scalp, urogenital, oral cavity, nasal or perinasal microbiome, most preferably the selective prebiotic disclosed can be used on the skin microbiome.

[0153] In certain embodiments, the selective prebiotic is contacted with a microbiome-comprising site of the skin for a defined period of time sufficient to allow interaction between the selective prebiotic and the skin microbiome. The contact time may be short-term, intermediate or prolonged, depending on the mode of application, the formulation type, galenic form and the intended use. Accordingly, the selective prebiotic may be contacted with the microbiome-comprising site for at least 0.5, 1, 2, 5, 10 or 15 minutes, for example in rinse-off or short-contact applications, or for at least 30, 60, 90, 120, 180 or 240 minutes, for example in leave-on or semi-occlusive applications. In further embodiments, particularly for leave-on formulations intended for prolonged skin residence, the selective prebiotic may be contacted with the microbiome-comprising site for extended durations of at least 480, 720, 960, 1100 or 1440 minutes. Such contact times can enable the selective prebiotic to exert its selective bacteriostatic and / or selective prebiotic function by interacting with the skin surface, the stratum corneum and the resident microbiome over a time period compatible with daily use conditions.BYH240210 FC -25- SPECIFIC EMBODIMENTS

[0154] The disclosure is further described in the following preferred embodiments.

[0155] Embodiment 1

[0156] A topical composition, preferably an emulsion or wash, more preferably a (W / O) emulsion, (O / W) emulsion or wash, for use on the skin comprising:

[0157] a. 0.01 to 8.00%, preferably 1.00 to 6.00% , more preferably 1.00 to 3.00% , most preferably 1% or 3% of a selective prebiotic comprising:

[0158] i. Xylitol,

[0159] ii. Anhydroxylitol, preferably as 1,4-Anhydro-D-xylitol, and iii. Xylitylglucoside,

[0160] b. at least one humectant,

[0161] c. at least one provitamin, vitamin and / or vitamin derivate selected from provitamin, vitamin B3 and / or a salt thereof, preferably niacinamide, provitamin, vitamin Bs and / or a salt thereof, preferably dexpanthenol and / or provitamin, vitamin E and / or a salt thereof, preferably tocopheryl acetate, and d. at least two lipids from the list comprising or consisting of ceramides, cholesterol, cholesterol esters, triglycerides, free fatty acids, free fatty acid derivates including glyceryl oleate and ethyl linoleate, caprylic capric triglyceride, Butyrospermum parkii (shea) butter, shea butter derivatives, squalane and / or squalene.

[0162] Embodiment 2

[0163] A semisolid topical composition, preferably a paste, an ointment, a gel or a cream, preferably a gel or a cream, for use on the skin comprising:

[0164] a. 0.01 to 8.00% (w / w), preferably 1.00 to 6.00% (w / w), more preferably 1.00 to 3.00% (w / w), most preferably 1% or 3% (w / w) of a selective prebiotic comprising:

[0165] i. Xylitol,

[0166] ii. Anhydroxylitol, preferably as 1,4-Anhydro-D-xylitol, and iii. Xylitylglucoside,BYH240210 FC -26- b. at least one humectant,

[0167] c. at least one provitamin, vitamin and / or vitamin derivate selected from provitamin, vitamin B3 and / or a salt thereof, preferably niacinamide, provitamin, vitamin Bs and / or a salt thereof, preferably dexpanthenol and / or provitamin, vitamin E and / or a salt thereof, preferably tocopheryl acetate, and d. at least two lipids from the list comprising or consisting of ceramides, cholesterol, cholesterol esters, triglycerides, free fatty acids, free fatty acid derivates including glyceryl oleate and ethyl linoleate, caprylic capric triglyceride, Butyrospermum parkii (shea) butter, shea butter derivatives, squalane and / or squalene.

[0168] Embodiment 3

[0169] A liquid topical composition, preferably an (O / W) emulsion, preferably a lotion, a solution or a suspension, more a lotion, for use on the skin comprising:

[0170] a. 0.01 to 8.00% (w / v), preferably 1.00 to 6.00% (w / v), more preferably 1.00 to 3.00% (w / v), most preferably 1% or 3% (w / v) of a selective prebiotic comprising:

[0171] i. Xylitol,

[0172] ii. Anhydroxylitol, preferably as 1,4-Anhydro-D-xylitol, and iii. Xylitylglucoside,

[0173] b. at least one humectant,

[0174] c. at least one provitamin, vitamin and / or vitamin derivate selected from provitamin, vitamin B3 and / or a salt thereof, preferably niacinamide, provitamin, vitamin Bs and / or a salt thereof, preferably dexpanthenol and / or provitamin, vitamin E and / or a salt thereof, preferably tocopheryl acetate, and d. at least two lipids from the list comprising or consisting of ceramides, cholesterol, cholesterol esters, triglycerides, free fatty acids, free fatty acid derivates including glyceryl oleate and ethyl linoleate, caprylic capric triglyceride, Butyrospermum parkii (shea) butter, shea butter derivatives, squalane and / or squalene.BYH240210 FC -27- Embodiment 4

[0175] The composition according to any one or more of embodiments 1 to 3, characterized in that the selective prebiotic consists of:

[0176] i. Xylitol,

[0177] ii. Anhydroxylitol, preferably as 1,4-Anhydro-D-xylitol,

[0178] iii. Xylitylglucoside,

[0179] iv. Water, and

[0180] v. Glucose,

[0181] and optionally the topical composition is free of additional alditols.

[0182] Embodiment 5

[0183] The composition according any one or more of embodiments 1 - 4, characterized in that the at least one humectant is from the group comprising or consisting of lactic acid, glycerin, pyrrolidone carboxylic acid, sodium pyrrolidone carboxylic acid, dexpanthenol, 1,2-hexanediol, 1,2-heptanediol and a composition comprising saccharide isomerate, water, citric acid and sodium citrate.

[0184] Embodiment 6

[0185] A composition according to any one or more of embodiments 1 - 5, characterized in that the selective prebiotic comprises i. 5.0 to 15.0% (w / v) Xylitol, preferably 10.0 to 12.0% (w / v) Xylitol, ii. 24.0 to 34.0% (w / v), Anhydroxylitol, preferably 1,4-Anhydro-D-Xylitol preferably 28.0 to 32.0% (w / v) Anhydroxylitol, preferably 1,4-Anhydro-D-Xylitol, and iii. 35.0 to 50.0% (w / v) Xylitylglucoside, preferably 40.0 to 45.0% (w / v) Xylitylglucoside.

[0186] Embodiment 7

[0187] A composition according to any one or more of embodiments 1 - 6, characterized in that the selective prebiotic consists of i. 5.0 to 15.0% (w / v) Xylitol, preferably 10.0 to 12.0% (w / v) Xylitol, ii. 24.0 to 34.0% (w / v) Anhydroxylitol, preferably 24.0 to 34.0% (w / v) 1,4-Anhydro-D-xylitol, more preferably 28.0 to 32.0% (w / v) Anhydroxylitol, most preferably 28.0 to 32.0% (w / v) 1,4-Anhydro-D-xylitol, iii. 35.0 to 50.0% (w / v) Xylitylglucoside, preferably 40.0 to 45.0% (w / v) Xylitylglucoside, iv. 12 to 20% (w / v) of Water, preferably 15 to 17% (w / v) Water, and iv. 0 to 5% (w / v) Glucose, preferably 1 to 4% (w / v) D-Glucose.BYH240210 FC -28- Embodiment 8

[0188] A composition according to any one or more of embodiments 1 - 7, characterized in that the selective prebiotic is the commercially available Aquaxyl™ composition, preferably 1% or 3% (w / v) or (w / w) of the Aquaxyl™ composition.

[0189] Embodiment 9

[0190] A composition according to any one or more of embodiments 1 - 8, characterized in that the composition has a pH from 3.8 to 5.5, preferably a pH from 3.8 to 4.5, 4.0 to 5.0, 4.4 to 5.5, 4.5 to 5.5 or 5.0 to 5.5, more preferably a pH from 4.0 to 5.5, most preferably a pH from pH 4.5 to pH 4.7, pH 4.5 to pH 5.5 or pH 4.4 to pH 5.5.

[0191] Embodiment 10

[0192] A composition according to any one or more of embodiments 1 - 9, characterized in that the composition is free of strong detergents, preferably free of sodium lauryl sulfate and sodium laureth sulfates, free of volatile siloxanes, preferably free of octamethylcyclotetrasiloxane (D4), decamethylcyclopentasiloxane (D5) and dodecamethylcyclohexasiloxane (D6), and / or free of preservatives, preferably free of parabens, methylisothiazolinone and / or mineral oils.

[0193] Embodiment 11

[0194] A composition according to any one or more of embodiments 1 - 10, characterized in that the composition is an emulsion, preferably a (W / O) emulsion, and the at least two lipids are Butyrospermum parkii (shea) butter, ethyl linoleate, squalane, caprylic capric triglyceride, cholesterol and / or ceramide.

[0195] Embodiment 12

[0196] A composition according to any one or more of embodiments 1 - 11, characterized in that the at least one humectant is glycerin, lactic acid, 1,2 -hexanediol, 1,2-heptanediol, pyrrolidone carboxylic acid, sodium pyrrolidone carboxylic acid and / or dexpanthenol.

[0197] Embodiment 13

[0198] A composition according to any one or more of embodiments 1 - 12, characterized in that the composition has a pH from pH 4.5 to pH 4.7 or from pH 4.4 to 5.5, preferably pH 4.5 to pH 4.7, pH 4.4 to pH 5.5 or pH 4.5 to pH 5.5.BYH240210 FC -29- Embodiment 14

[0199] A composition according to any one or more of embodiments 1 - 13, characterized in that the composition is cosmetic or non-therapeutic.

[0200] Embodiments 15

[0201] A composition according to any one or more of embodiments 1 - 13 for use in the treatment and / or prevention of a skin disease, preferably for use in the treatment and / or prevention of an acne and / or an eczema skin disease, more preferably for use in the treatment and / or prevention of atopic dermatitis, contact dermatitis, dyshidrotic eczema and / or nummular eczema, most preferably for use in the treatment and / or prevention of atopic dermatitis, contact dermatitis, dyshidrotic eczema and / or nummular eczema in newborns, infants and / or children.

[0202] Embodiment 16

[0203] A composition according to embodiment 15, characterized in that the selective prebiotic supports the growth of beneficial bacteria Staphylococcus epidermidis and / or reduces the growth of pathogenic or opportunistic pathogenic bacteria Staphylococcus aureus, and / or Cutibacterium acnes, and / or reduces the growth of commensal bacteria Corynebacterium striatum, preferably when beneficial bacteria are in growth competition with pathogenic and / or opportunistic pathogenic and / or commensal bacteria.

[0204] Embodiment 17

[0205] A composition according to embodiment 15 or 16, characterized in that the composition supports the growth of beneficial bacteria Staphylococcus epidermidis and / or reduces the growth of pathogenic or opportunistic pathogenic bacteria Staphylococcus aureus, and / or Cutibacterium acnes, and / or reduces the growth of commensal bacteria Corynebacterium striatum, preferably when beneficial bacteria are in growth competition with pathogenic and / or opportunistic pathogenic and / or commensal bacteria.

[0206] Embodiment 18

[0207] A composition according to any one or more of embodiments 15 - 17, characterized in that the topical composition is a (W / O) emulsion, preferably a cream.

[0208] Embodiment 19

[0209] A composition according to any one or more of embodiments 15 - 17, characterized in that the topical composition is an (O / W) emulsion, preferably a lotion.BYH240210 FC -30- Embodiment 20

[0210] A composition according to any one or more of embodiments 15 - 18, characterized in that the composition comprises at least of Butyrospermum parkii (shea) butter, squalane, caprylic capric triglyceride, ceramide, ethyl linoleate, and / or cholesterol.

[0211] Embodiment 21

[0212] A composition according to embodiment 18 or 20, characterized in that the composition comprises lactic acid, glycerin, pyrrolidone carboxylic acid, sodium pyrrolidone carboxylic acid, dexpanthenol, 1,2-hexanediol and / or 1,2-heptanediol.

[0213] Embodiment 22

[0214] A composition according to embodiment 18, 20 or 21, characterized in that the composition comprises dexpanthenol, niacinamide and / or tocopheryl acetate.

[0215] Embodiment 23

[0216] A composition according to embodiment 22, characterized in that the topical composition is a (W / O) emulsion, preferably a cream, has pH 4.5 to pH 4.7 and comprises:

[0217] a. 3% (w / w) of a selective prebiotic consisting of:

[0218] i. Xylitol,

[0219] ii. Anhydroxylitol, preferably as 1,4-Anhydro-D-xylitol,

[0220] iii. Xylitylglucoside,

[0221] iv. Water, and

[0222] v. Glucose,

[0223] b. lactic acid, glycerin, pyrrolidone carboxylic acid, sodium pyrrolidone carboxylic acid and / or dexpanthenol,

[0224] c. dexpanthenol, niacinamide and / or tocopheryl acetate, and

[0225] d. Butyrospermum parkii (shea) butter, squalane, caprylic capric triglyceride, ceramide, ethyl linoleate, and / or cholesterol.

[0226] Embodiment 24

[0227] Non-therapeutic use of a composition according any one or more of embodiments 1 - 14, characterized in that the composition is for strengthening the physical, biochemical and microbial layer of the skin, wherein the skin is newborn, infant, child, adolescent, adult or mature skin, preferably newborn and / or infant skin.BYH240210 FC -31- Embodiment 25

[0228] Topical Use of a composition comprising:

[0229] i. Xylitol,

[0230] ii. Anhydroxylitol, preferably 1,4-Anhydro-D-xylitol, and

[0231] iii. Xylitglucoside,

[0232] as selective prebiotic, characterized in that the selective prebiotic has a selective bacteriostatic and / or selective prebiotic function.

[0233] Embodiment 26

[0234] Use according to embodiment 25, characterized in that the composition for topical use consists of:

[0235] i. Xylitol,

[0236] ii. Anhydroxylitol, preferably 1,4-Anhydro-D-xylitol,

[0237] iii. Xylitylglucoside,

[0238] iv. Water, and

[0239] v. Glucose.

[0240] Embodiment 27

[0241] Use according to embodiment 25 or 26, characterized in that composition comprises:

[0242] i. 5.0 to 15.0% (w / v) Xylitol, preferably 10.0 to 12.0% (w / v) Xylitol,

[0243] ii. 24.0 to 34.0% (w / v) Anhydroxylitol, preferably 24.0 to 34.0% (w / v) 1,4- Anhydro-D-xylitol, more preferably 28.0 to 32.0% (w / v) Anhydroxylitol, most preferably 28.0 to 32.0% (w / v) 1,4-Anhydro-D-xylitol, and

[0244] iii. 35.0 to 50.0% (w / v) Xylitylglucoside, preferably 40.0 to 45.0% (w / v) Xylitylglucoside.

[0245] Embodiment 28

[0246] Use according to any one or more of embodiments 25 to 27, characterized in that the composition comprises or consists of:

[0247] i. 5.0 to 15.0% (w / v) Xylitol, preferably 10.0 to 12.0% (w / v) Xylitol,

[0248] 11. 24.0 to 34.0% (w / v) Anhydroxylitol, preferably 24.0 to 34.0% (w / v) 1,4- Anhydro-D-xylitol, more preferably 28.0 to 32.0% (w / v) Anhydroxylitol, most preferably 28.0 to 32.0% (w / v) 1,4-Anhydro-D-xylitol,BYH240210 FC -32- iii. 35.0 to 50.0% (w / v) Xylitylglucoside, preferably 40.0 to 45.0% (w / v) Xylitylglucoside,

[0249] iv. 12 to 20% (w / v) of Water, preferably 15 to 17% (w / v) Water, and

[0250] v. 0 to 5% (w / v) Glucose, preferably 1 to 4% (w / v) D-Glucose.

[0251] Embodiment 29

[0252] Use of a composition according to any one or more of embodiments 25 to 28, characterized in that the selective prebiotic is the commercially available Aquaxyl™ composition, preferably use of 1 or 3% (w / v) or (w / w) of Aquaxyl™ composition as selective prebiotic.

[0253] Embodiment 30

[0254] Use according to any one or more of embodiments 25 to 29, characterized that the topical composition is an emulsion, preferably a (W / O) emulsion, more preferably a cream.

[0255] Embodiment 31

[0256] Use according to any one or more of embodiments 25 to 29, characterized that the topical composition is an emulsion, preferably a (O / W) emulsion, more preferably a lotion.

[0257] Embodiment 32

[0258] Use according to any one or more of embodiments 25 to 29, characterized that the topical composition is a wash.

[0259] Embodiment 33

[0260] Use according to any one or more of embodiments 25 - 32, characterized in that the selective prebiotic has a selective bacteriostatic and / or prebiotic function on skin, scalp, urogenital, oral cavity, nasal or perinasal microbiome, preferably on skin microbiome.

[0261] Embodiment 34

[0262] Use according to any one or more of embodiments 25 - 31, characterized in that the composition is contacted with a microbiome comprising site for at least 0.5, 1, 2, 5, 10, 15, 30, 45, 60, 90, 120, 180, 240, 480, 720, 960, 1100, or 1440 minutes.

[0263] Embodiment 35

[0264] Use according to any one or more of embodiments 25 - 29 and 32, characterized in that the composition is contacted with a microbiome comprising site for 0.5 - 15, 1 - 10 and / or 5 - 10 minutes.BYH240210 FC -33- Embodiment 36

[0265] Use according to any one or more of embodiments 25 - 35, characterized in that the composition is administered less than three times every 24h, preferably administered once every 24h.

[0266] Embodiment 37

[0267] Use of a composition according to any one or more of embodiments 25 - 36, characterized in that the ratio is i. Xylitol to ii. Anhydroxylitol, most preferably 1,4-Anhydro-D-xylitol to iii. Xylitylglucoside: i. I to ii. 1.6 to 6.8 to iii. 2.33 to 10, preferably !. I toii. 1.6 to 4.8 to iii. 2.333 to 7, more preferably i. 1 to ii. 1.666 to 2.333 to iii. 2.333 to 3.333, most preferably i. 1 to ii.

[0268] 2.333 to iii. 3.333.

[0269] Embodiment 38

[0270] Use of a composition according to any one or more of embodiments 25 - 37, characterized in that the composition of the selective prebiotic is free of additional alditols.

[0271] Embodiment 39

[0272] Use of a composition according to any one or more of embodiments 25 - 38, characterized in that the selective prebiotic supports the growth of beneficial bacteria Staphylococcus epidermidis and / or reduces the growth of pathogenic or opportunistic pathogenic bacteria Staphylococcus aureus, and / or Cutibacterium acnes, and / or reduces the growth of commensal bacteria Corynebacterium striatum, preferably when beneficial bacteria are in growth competition with pathogenic and / or opportunistic pathogenic and / or commensal bacteria.

[0273] DEFINITIONS

[0274] The terms referring to topical dosage forms such as “liquid”, “semisolid”, “emulsion”, “(W / O) emulsion”, “(O / W) emulsion”, “cream”, “lotion”, “wash”, “solution”, “suspension” as used herein are based on Buhse et al., Int. J. Pharm. 2005, 295, 101-112.

[0275] The term “skin condition” or “cutaneous condition” as used herein comprises cosmetic and / or medical conditions that affect the integumentary system i.e. the organ system that encloses the body and includes skin, nails and related muscles and glands.

[0276] The term “cosmetic skin condition” or “cosmetic cutaneous condition” as used herein comprises non-medical cosmetic conditions that affect the integumentary system i.e. the organ system that encloses the body and includes skin, nails and related muscles and glands.BYH240210 FC -34- The term “skin disease” or “cutaneous disease” as used herein comprises non-cosmetic, medical conditions that affect the integumentary system i.e. the organ system that encloses the body and includes skin, nails and related muscles and glands. Examples of skin diseases include acne, psoriasis, and eczema skin disease, such as eczema skin diseases atopic dermatitis, contact dermatitis, dyshidrotic eczema and / or nummular eczema.

[0277] The term “alditol” as used herein comprises sugar alcohols, polyhydric alcohols, polyalcohols or glycitols which describe organic, polyol compounds typically derived from sugars wherein each carbon atom is attached to one hydroxyl (-OH) group. An Alditol can occur naturally or can be derived by hydrogenating a sugar. Their general formula is HOCH2(CHOH)nCH2OH and they usually exist as chains or most of the alditols are chains not cyclic. The number of carbons in the alditol molecule typically range from two (2) to twenty-four (24) but can also be higher. Most alditols have five- or six-carbon. Examples of alditols comprise ethylene glycol, glycerol, erythritol, threitol, arabitol, xylitol, ribitol, mannitol, sorbitol, galactitol, fucitol, iditol, inositol, volemitol, isomalt, maltitol, lactitol, maltotriitol, maltotetraitol and polyglycitol. Alditols can be used as thickeners and sweeteners also in combination with artificial sweeteners. The term “alditol derivate” as used herein comprises different derivates of alditols. The term comprises dehydrated alditols that can form cyclic ethers such as dehydrated sorbitol can form cyclic ethers in sorbitan which can be further dehydrated to form the bicyclic compound isosorbide. Dehydration products of the five-carbon chain alditols comprise the dehydration products of arabitol (1,4-Anhydro-D-arabitol, 1,5-Anhydro-D-arabitol and 2,5-Anhydro-D-arabitol), Xylitol (1,4-Anhydro-D-xylitol, 1,5-Anhydro-D-xylitol and 2,5-Anhydro-D-xylitol) and ribitol (1,4-Anhydro-D-ribitol, 1,5-Anhydro-D-ribitol and 2,5-Anhydro-D-ribitol). The term “alditol derivate” can also refer to a glucoside of an alditol. These alditol derivates comprise glucosides in which an alditol is bound via a glycosidic bond to glucose. Examples of alditol glucosides include glucosides of five-carbon alditols such as arabitol glucoside, Xylitylglucoside or ribitol glucoside and glucosides of six-carbon alditols such as mannitolglucoside, sorbitolglucoside, galactitolglucoside, fucitolglucoside, iditolglucoside, inositolglucoside.

[0278] Compositions according to this disclosure can comprise most preferably Xylitol and at least one Xylitol dehydration product from 1,4-Anhydro-D-xylitol, 1,5-Anhydro-D-xylitol and / or 2,5-Anhydro-D-xylitol and Xylitylglucoside, preferably a D-Glucose glycosylation product with Xylitol, in a ratio of Xylitol at 1 to Xylitol dehydration product at 1.6 to 6.8, preferably at 1.6 to 4.8, more preferably at 1.666 to 2.333, most preferably at 2.333, to Xylitylglucoside,BYH240210 FC -35-preferably a D-Glucose glycosylation product with Xylitol, at 2.33 to 10, preferably at 2.333 to 7, more preferably at 2.333 to 3.333, most preferably at 3.333. Preferably a ratio of Xylitol at 1 to Xylitol dehydration product at 1.6 to 4.8 to Xylitylglucoside, preferably a D-Glucose glycosylation product with Xylitol, at 2.333 to 7, more preferably Xylitol at 1 to Xylitol dehydration product at 1.666 to 2.333 to Xylitylglucoside, preferably as D-Glucose glycosylation product with Xylitol, at 2.3 to 3.333, most preferably Xylitol at 1 to Xylitol dehydration product at 2.333 to Xylitylglucoside, preferably as D-Glucose glycosylation product with Xylitol, at 3.333.

[0279] The term “prebiotic” as used herein refers to a substance and / or a combination of components that can include a substrate, including carbohydrates, lipids or fibers that promote the growth of the microbiota in particular the bacteria comprised in the microbiota. Examples of prebiotics are substances such as (poly-)phenols, poly unsaturated fatty acids or saccharides and their derivatives like alditols or combinations of alditols and alditol derivates. A preferred example of prebiotics are saccharides and their derivatives in particular alditols and / or alditol derivatives and combination thereof.

[0280] The term “selective prebiotic” as used herein can refer to a prebiotic that can exert a bacteriostatic function on bacteria that have a negative effect on the host while it has no or a reduced bacteriostatic function on host-beneficial bacteria and therefore selectively supports the increase of number and / or ratio of the host-beneficial bacteria in a given microbiota. A “selective prebiotic” can also refer to a prebiotic that selectively supports the growth of host-beneficial bacteria while it does not or at reduced levels support the growth of bacteria hat have a negative effect on the host thereby increasing the increase of number and / or ratio of the host-beneficial bacteria in a given microbiota. Further effects of a selective prebiotic can include that it selectively inhibits or reduces the adhesion of bacteria hat have a negative effect on the host and / or selectively inhibits the biofilm formation of these bacteria and / or inhibits or reduces their biofilm formation and / or inhibits or reduces their re-adhesion while it does not have such a function or at reduced levels in host-beneficial bacteria and therefore selectively supports the increase of number and / or ratio of the host-beneficial bacteria in a given microbiota. A selective prebiotic can also exert a function via one or more of these mechanisms to support the increase of number and / or ratio of the host-beneficial bacteria in a given microbiota.

[0281] The term “selective prebiotic” as used herein particularly refers to a prebiotic that selectively supports and / or promotes the growth of host beneficial components of the microbiota and / or reduces or hampers the growth of parts of the microbiota that can be detrimental to the hostBYH240210 FC -36-such as obligate pathogens or opportunistic pathogens. The term “selective prebiotic” preferably pertains to a substance or combination comprising alditols and / or alditol derivatives and combination thereof. More preferably a selective prebiotic wherein the selective prebiotic has a selective bacteriostatic and / or a selective growth supporting function. Most preferably the term “selective prebiotic” pertains to a substance or combination comprising alditols and / or alditol derivatives and combination thereof wherein the selective prebiotic has a selective bacteriostatic and / or a selective growth supporting function.

[0282] The term “moisturizer” as used herein refers to an agent that can increase the hydration level of the skin. Moisturizers can smoothen and / or hydrate the skin; they are classified by their mode of action. Three different classes of moisturizers can be distinguished, namely emollients, humectants and occlusives by their mode of action. An agent classified as moisturizer may be an emollient, humectant and / or occlusive.

[0283] The term “humectant” as used herein refers to an agent that can bring water in and / or bind water in the stratum corneum. A humectant can increase the hydration of the stratum corneum. The water can be attracted from deeper layers in the skin and / or from the air. Examples of humectants include: 1,2-hexanediol, 1,2-heptanediol, a composition comprising saccharide isomerate, water, citric acid and sodium citrate which is commercially available under the name “Pentavitin™”, Aquaxyl™, pyrrolidone carboxylic acid (PCA) and its’ derivates including sodium PCA, glycerin, dexpanthenol and / or lactic acid.

[0284] The term “vemix caseosa like lipids” as used herein refers to lipids that structurally and / or functionally resemble or are lipids or lipid-like constituents that can be found in the vernix caseosa such as triglycerides, different kinds of fatty acids or synthetic derivative forms of these fatty acids, ceramides, cholesterol esters and cholesterol. Vernix caseosa like lipids as used herein can include shea butter or Butyrospermum parkii butter, free fatty acids and the derivatives comprising glyceryl oleate and ethyl linoleate, squalane and squalene, caprylic capric triglyceride and ceramides including ceramide 3 and ceramide NP. Natural vernix caseosa consists of various types of lipids including Cholesterol esters, Ceramides, Triglycerides Cholesterol, Free fatty acids, Phospholipids Wax esters, Squalene, Wax diesters, Cerebrosides, Cholesterol sulphate. Topical compositions according to this disclosure comprise at least two lipids from the list comprising or consisting of ceramides, cholesterol, cholesterol esters, triglycerides, free fatty acids, squalene or synthetic versions thereof including glyceryl oleate and ethyl linoleate, caprylic capric triglycerides, Butyrospermum parkii (shea) butter,BYH240210 FC -37- Butyrospermum parkii (shea) butter derivates including shea butter glycereth-8-esters and / or squalane.

[0285] Without being bound by theory, the inventors believe that the inclusion of these lipids can result in the formation of a vernix caseosa like lipid complex on the skin. A vemix caseosa like lipid complex can support the physical barrier function of the skin. The vemix caseosa like lipid complex can include glyceryl oleate, ethyl linoleate, ceramides, Butyrospermum parkii (or shea) butter and shea butter derivates or modified shea butter, cholesterol, cholesterol esters, squalene, squalane, and caprylic / capric triglyceride. Each of these lipids corresponds to fundamental categories found in vernix, contributing to its protective properties and can be a vemix caseosa like lipid according to this disclosure. Synthetic derivatives of lipids or lipid-like constituents present in the vernix caseosa include esterification products of an alcohol such with a non-esterified fatty acid (NEFA) which is constituent of the vemix caseosa, for instance ethanol and linoleic acid to form ethyl linoleate or glycerol and oleic acid to form glyceryl oleate. The inclusion of synthetic derivatives of vernix caseosa like lipids can for instance improve the stability of the biologic vemix caseosa ingredient in a topical composition according to the disclosure. Shea butter and shea butter derivatives include shea butter that has been modified to increase water solubility such as shea butter glycereth-8 esters (INCI) or a shea butter that has been transesterified with glycereth-8.

[0286] The term “skin” as used herein can refer to different compositions of the skin of a subject inter alia depending on the age of the subject. A skin can belong to a fetus, a newborn (from birth to 1 month), an infant (1 month to 3 years after birth), a child (from birth to adolescence or 10 to 14 years after birth), an adolescent (10 to 18 years after birth), an adult (18 to 65 years after birth) and / or a senior and be mature skin (65 and more years after birth). Compositions according to the disclosure as disclosed herein are preferably for use on newborn, infant and / or child skin, even more preferably for use on newborn and / or infant skin. Uses according to the disclosure as disclosed herein are preferentially for use on newborns, infants and / or children, more preferably for use on newborns and / or infants.

[0287] The term “support all barrier function of the skin” as used herein refers to an effect that achieves an improvement of all three functions or barriers (biochemical function or barrier, microbial function or barrier and physical function or barrier) of the skin. Compositions according to this disclosure can simultaneously support all three barrier functions, wherein simultaneously means that the improvements of the function can happen at the same time and / or with some timely delay between improvements of the respective barriers. Compositions according to thisBYH240210 FC -38-disclosure can also have synergistic effect regarding the improvement of the barrier functions of the skin. For instance, selective prebiotics according to this disclosure can interact with other ingredients of the compositions such as the vitamins and the vernix caseosa like lipids to result in an overall increased improvement of all three barrier functions of the skin and not just the microbial barrier function.

[0288] An improvement of the physical barrier function of the skin can for example be assessed by transmission electron microscopy (TEM), scanning electron microscope (SEM) and / or spectroscopy. An improvement of the biochemical barrier function of the skin can for example be assessed by corneometry. An improvement of the microbial layer can for example be assessed by determining the Shannon diversity factors or Shannon diversity index of the microbial species present.

[0289] The term “provitamin” as used herein can refer to organic molecules that are essential for organisms in minor quantities to support proper metabolic function either directly or after a metabolic process has transformed them. Such essential nutrients can be present in different metabolic states such as provitamins which can be converted by metabolic processes within such organisms to vitamins. Examples of provitamins include provitamin Bs or dexpanthenol or pantothenol, or D-panthenol that can be converted into pantothenic acid or Vitamin Bs. Pantothenic acid or Vitamin Bs can play an essential role in dermatological metabolism as part of coenzyme A. An example of a salt of a provitamin of vitamin E or tocopherol, which is a group of lipid-soluble antioxidants that can inhibit the production of reactive oxygen species molecules in the skin and that prevent lipid peroxidation and protect the integrity of cell membranes, is a / / ra-tocopherol acetate, a-tocopheryl acetate or vitamin E acetate.

[0290] The term “vitamer” of a particular vitamin as used herein refers to one of several related molecules that perform the functions of said vitamin and also prevent a vitamin-deficiency of said vitamin. Examples of vitamers of vitamin B3 are nicotinic acid (or niacin), nicotinamide (niacinamide) or nicotinamide riboside that can all be converted by metabolic processes within such organisms into nicotinamide adenine dinucleotide (NAD). The provitamins, vitamins, derivates and / or salts thereof disclosed as part of compositions according to this disclosure can support skin hydration and promote skin homeostasis.

[0291] The term “newborn” as used herein can refer to any human subject between birth to about 1 month of age. The term “infant” as used herein can refer to any human subject between birth and three years of age. The term “child” as used herein can refer to any human subject betweenBYH240210 FC -39-the stages of birth and puberty. It can refer to a human subject between birth to ten to fourteen years of age.

[0292] The term “pH of the composition” as used herein refers to the pH of the composition or the pH of the water phase of the composition where technically appropriate as determined by an expert in the field. Usually pH of a (W / O) emulsion, preferably a cream, refers to the pH of the water phase of the composition, while pH of a wash or an (O / W) emulsion, preferably a lotion, refers to the pH of the composition as a whole.

[0293] The term “leave-on” composition or product as used herein can refer to topical formulations intended to be applied to the skin and remain in prolonged contact time without being rinsed or washed off after application for instance in a lotion or cream, wherein prolonged contact time can mean that the leave-on composition is contacted for at least 30, 45, 60, 90, 120, 180 or 240 minutes, but also for extended durations such as 480, 720, 960, 1100 or 1440 minutes.

[0294] The term “rinse-off’ composition or product as used herein can refer to topical formulations intended to be applied to the skin for a short contact time and subsequently removed by rinsing with water after application for instance in a wash composition, wherein short contact time can mean that the leave-on composition is contacted for at least 0.5, 1, 2, 5 or 10 minutes, but also for not more than 2, 5, 10 or 15 minutes. The term short contact times includes 0.5 - 15, 1 - 10 and / or 5 - 10 minutes.

[0295] EXAMPLES

[0296] The present disclosure is now illustrated by the following non-limiting examples Example 1

[0297] Several ingredients were tested for their ability to act as prebiotic and / or as selective prebiotic. In particular different derivates of mono-, oligo and polysaccharides were tested. Their ability to support or selectively support the growth of Staphylococcus epidermidis and control or selectively control the growth of Staphylococcus aureus in a competitive scenario (FIG. 1). Methodology

[0298] Evaluation of the effect of test compounds product A [Aquaxyl™, a combination of three molecules Xylitylglucoside (35.0 to 50.0%), Anhydroxylitol (24.0 to 34.0%) and Xylitol (5 - 15%)], product B (AD-RESYL®, comprising fructose-based oligo- and polysaccharides Ophiopogon japonicus'y product C (a galactooligosaccharide), product C’ (marshmallow extract) and their combinations was assessed on the proliferation of a mix of 2 bacterial strainsBYH240210 FC -40- S. aureus (ATCC® 6538™, Gram +) and S. epidermidis (ATCC® 14990™, Gram +) on reconstructed human epidermis (RHE) produced with keratinocytes from an 8-month-old infant in a Mueller Hinton agar at 37°C. The mix of bacterial strains was prepared to deposit approximatively 5* 106CFU / RHE for S. aureus and S. epidermidis. The bacterial counting was made using qPCR technology.

[0299] The RHE were treated (topical application; 50 pl / RHE) with the test compounds, the combinations or water (control or non-infected condition) and pre-incubated for 24 hours. After pre-incub ati on, the medium was replaced and topical treatments were renewed, the bacterial mix was then added or not (non-infected condition) on the RHE. After 4 hours of incubation, the RHE were rinsed by 4 successive washes with a PBS solution and incubated for 20 hours. 5 biological replicates per condition were performed.

[0300] Results

[0301] After 4 hours of incubation and 20 hours of proliferation, the proportion of each bacterium on RHE in the control was:

[0302] - S. aureus-. 78% of total adhered bacteria and

[0303] - S. epidermidis'. 22% of total adhered bacteria.

[0304] No bacteria were found on the non-infected controls.

[0305] Product A alone was the product able to promote S. epidermidis proliferation (18% increase vs control; bacterial counts 7.96 105vs 6.76 105) while also inhibit S. aureus proliferation (33% decrease vs control; bacterial counts 1.86 106vs 2.41 106. Therefore, cultivation with product A increased the proportion of S. epidermidis to 31% and decreased that of S. aureus to 69% in this competitive growth setup. The same ratio of 31% for S. epidermidis to 69% of S. aureus was also observed for the product A + product C and for product A + product B + product C treatments. The best increase in S. epidermidis numbers were achieved in product A treatment. The results support the use of alditols or compositions of alditols with alditol derivates and alditol glucosylation products as selective prebiotics.

[0306] Example 2

[0307] In a follow-up experiment the impact of an increase in the concentration of Xylitol in the Aquaxyl™ composition relative to the xylitol derivates (Xylitylglucoside and Anhydroxylitol) such as selective support of growth or selective control of growth was tested (FIG. 2).

[0308] MethodologyBYH240210 FC -41- The prebiotic effects of the compounds Aquaxyl™ and Xylitol, at different concentrations of Xylitol (Aquaxyl - 3% or Xylitol - 0.36% = 0.36%, Aquaxyl + Xylitol - 3% + 0.64% or Xylitol - 1% = 1% and Aquaxyl + Xylitol - 3% + 2.14% or Xylitol - 2.5% = 2.5%) and in combination, were evaluated on the growth of four bacterial strains on strain-specific tryptone agar medium:

[0309] • Staphylococcus aureus ATCC® 6538™ (5. aureus),

[0310] • Staphylococcus epidermidis ATCC® 14990™ (5. epidermidis),

[0311] • Corynebacterium striatum ATCC® 6940™ (C. striatum),

[0312] • Cutibacterium acnes ATCC® 6919™ (C. acnes).

[0313] These effects were compared to those of 1% glucose (control) over a duration of 24, 48 hours or 96h, depending on the strains. Bacterial growth was measured by optical densiometry at 600nm wavelength (DOeoonm). 3 biological replicates per conditions were performed.

[0314] Results

[0315] Xylitol alone inhibited the growth of all tested bacteria. A significant increase in the growth of S. epidermidis was only observed after incubation in a composition comprising Xylitol, Anhydroxyxylitol and Xylitylglucoside.

[0316] Aquaxyl™ supported an increase in the growth of S. epidermidis over a prolonged period compared to the glucose control, while for the pathogenic or opportunistic pathogenic S. aureus, C. acnes and the commensal bacterium C. striatum it led to a reduced growth compared to the glucose control (1% and 0.1%) and the growth phase of these bacteria reached a plateau phase in their growth much sooner than S. epidermidis. The addition of Xylitol to Aquaxyl™ had little overall impact on the growth of the tested bacteria.

[0317] Example 3

[0318] In a follow-up in vitro experiment the effectiveness of Aquaxyl™ in a topical composition to support the microbial barrier function was tested and compared to other agents (FIG. 3).

[0319] Methodology

[0320] Adult RHE (reconstructed human epidermis) was treated with a cytokine mix to replicate Atopic dermatitis (RHE-AD). D0-D8: Maturation of the tissues, D8: 1stapplication of the different treatment regimens 3 replicates per sample).

[0321] No agent added (No treatment).

[0322] A cream comprising Aquaxyl™ at 3% (w / w) of the composition (chassis - Aquaxyl™).BYH240210 FC -42- A similar cream comprising product C (a galactooligosaccharide) at 0.75% (w / w) of the composition (chassis - galactooligosaccharide).

[0323] A systemic tofacitinib (a JAK / STAT signaling inhibitor) control (tofacitinib control).

[0324] D9: removal of excess compound (cotton swab / change of medium); DIO: S. aureus was added at 5xl06bacteria per RHE topically to RHE- AD after renewal of the topical treatment with the test products (and of the cytokine mix + / - tofacitinib systemically). After a 4h incubation (adhesion step), unattached S. aureus will be rinsed off. The number of attached S. aureus was quantified by CFU count; D12: read out, bacterial proliferation was quantified by CFU count (48h).

[0325] Results

[0326] Only a small proportion adheres firmly after 4 hours of contact (4h), anti-inflammatory treatment in the tofacitinib control increased adherence. There was a 1165-fold increase in S. aureus in the no treatment samples and a 949-fold increase in the tofacitinib control, while S. aureus load was efficiently controlled at only a 3 -fold increase 48h after S. aureus inoculation in the “chassis - Aquaxyl™” treatments compared to the number of S. aureus counted after adhesion in these samples. The load of S. aureus was reduced by a factor of 25 in the “chassis - galactooligosaccharide” treatments. The magnitude of effect on S. aureus load after 48h is comparable for the chassis - galactooligosaccharide and chassis - Aquaxyl treatment. The difference between the chassis - galactooligosaccharide and chassis - Aquaxyl treatment is not significant from a statistical point of view (p value = 0.7, Mann Whitney test).

[0327] Conclusion

[0328] The results of the study presented here, along with supportive literature, suggested that Aquaxyl™ is capable of delivering a selective prebiotic effect. This is evidenced by its ability to support the growth of S. epidermidis while controlling S. aureus, particularly when these two bacteria are in competition, as is the case in the human skin microbiome. Additionally, a bacteriostatic effect of Aquaxyl™, potentially attributed to Xylitol, on pathogenic bacteria was observed. Additionally, Aquaxyl™ in combination with a fructose-based prebiotic such as product B is not detrimental for the selective prebiotic effect of Aquaxyl™. Moreover, the selective prebiotic effect on S. epidermidis is mediated by a synergistic or additive effect of Xylitol with Anhydroxyxylitol and Xylitylglucoside. The bacteriostatic effect of Aquaxyl™ on pathogenic S. aureus can be used in topical products such as creams to support the microbial barrier function of the skin.BYH240210 FC -43- Example 4

[0329] In order to assess the effect on the skin microbiome of a selective prebiotic comprising Xylitol, Anhydroxyxylitol and Xylitylglucoside or consisting of Xylitol, Anhydroxyxylitol and Xylitylglucoside, Glucose and Water in real-life conditions, an in-home use test (IHUT) was performed with infants (age: 18 to 36 months) and children (3 to 10 years of age) under dermatological and pediatrician control (FIG. 4, FIG. 5).

[0330] Methodology

[0331] A lotion, (O / W) emulsion, comprising Aquaxyl™ at 1 % (w / w) of the lotion composition was applied daily for 28 days IHUT, whereby 2 - 3g (infants) or 4 - 5g (children) of the lotion were applied in each application. The lotion composition also comprised glycerin, 1,2-hexanediol, dexpanthenol, sodium pyrrolidone carboxylic acid, niacinamide, tocopheryl acetate, ceramide NP, squalane, ethyl linoleate, caprylic / capric triglyceride, butyrospermum parkii butter designed to mimic the composition and protective properties of vernix caseosa. Treated subjects were asked to retain their usual wash product and regimen before applying the lotion. The product was applied at least once daily by parents or caregivers to the skin of infants and children over the defined period of 28 days. Clinical evaluation was performed at the beginning and end of the study, under supervision of dermatologists and pediatricians. Skin microbiota load and skin microbiome diversity were assessed.

[0332] Total microbial load before treatment (day 0) and after 28 days (day 28) of treatment was analyzed by 16S rRNA quantification from forearm skin swaps as means of technical triplicates (Fig. 4). Microbial alpha diversity (a-diversity) was also evaluated by 16S rRNA sequencing (Fig. 5) (according to Lluch et al.; The Characterization of Novel Tissue Microbiota Using an Optimized 16S Metagenomic Sequencing Pipeline. PLoS One, 2015 Nov 6;10(l 1)). Alpha diversity was analyzed using different indices as represented in Fig. 5 (median + interquartile), group 1) Observed, group 2) Chaol, group 3) Shannon, group 4) Simpson, group 5) Inverse Simpson and group 6) Phylogenetic Diversity (PD).

[0333] A total of 44 human skin swabs and 4 unused skin swabs (SNC-MAT-UnS) and 6 DNA extraction environmental controls (VNC-EXT-Wat) were used.

[0334] Environmental controls included:

[0335] SNC-MAT-UnS: Study Negative Control for Material with Unused Swab as starting material. VNC-EXT-Wat: Vaiomer Negative Control for Extraction with Water as starting material VNC-QTY-Wat: Vaiomer Negative Control for Quantitation with Water as starting material.BYH240210 FC -44- Results

[0336] After 28 days lotion usage skin barrier improved. Skin dryness improved for both infants and children at DI, D2, and D28 based on corneometric analysis, while skin pH remained constant. An increase of the microbiota load in the skin microbiome in both groups infant (n.s.) and children (p=0.026) were observed. Alpha diversity was also evaluated and there was an increase in skin microbiome diversity in both groups (infants and children). When using the observed index the alpha diversity increased from dO to d28 for children (p=0.022) was statistically significant with a Kruskal-Wallis test. For the other indices, statistical significance was not reached; however, the trend indicated a direction towards greater skin microbiome diversity. Cutaneous tolerability assessment on body and face for the products in both studies showed that they were very well tolerated for subjects with dry and very dry skin.

[0337] Conclusion

[0338] The results of the study presented here, suggested that a lotion comprising Aquaxyl™ is capable of providing a positive effect on the skin microbiome of pediatric subjects. This was shown by its ability to support the increase in microbial biomass and an increase of the diversity of the taxa present in the skin microbiome. The use of topical emollients whose formulation into the lotion composition was based on mimicking the vernix caseosa composition proved beneficial to skin development. Skin moisturization improved during the 28 days of lotion usage. Dry skin is less flexible than moisturized skin, wherefore a well moisturized skin experiences less cracking or mechanical damage to the physical function during movement and is less itchy causing less scratching and therefore less reduction of the physical barrier function. The results suggest that the use of the tested lotion comprising Aquaxyl™ has a beneficial effect in early -age skincare contributing to the maintenance of skin barrier integrity and potentially prevent the development of atopic dermatitis (AD) and eczema as the current approach to minimize the risk of AD development includes the use of correctly formulated topical emollients and mild washing.

Claims

BYH240210 FC -45- CLAIMS1. A topical composition, preferably an emulsion or wash, more preferably a (W / O) emulsion, (O / W) emulsion or wash, for use on the skin comprising:a. 0.01 to 8.00%, preferably 1.00 to 6.00%, more preferably 1.00 to 3.00%, most preferably 1% or 3% of a selective prebiotic comprising:i. Xylitol,ii. Anhydroxylitol, preferably as 1,4-Anhydro-D-xylitol, and iii. Xylitylglucoside,b. at least one humectant,c. at least one provitamin, vitamin and / or vitamin derivate from provitamin, vitamin B3 and / or a salt thereof, preferably niacinamide, provitamin, vitamin Bs and / or a salt thereof, preferably dexpanthenol and / or provitamin, vitamin E and / or a salt thereof, preferably tocopheryl acetate, andd. at least two lipids from the list comprising or consisting of ceramides, cholesterol, cholesterol esters, triglycerides, free fatty acids, free fatty acid derivates including glyceryl oleate and ethyl linoleate, caprylic capric triglyceride, Butyrospermum parkii (shea) butter, shea butter derivatives, squalane and / or squalene.

2. The composition according to claim 1, characterized in that the at least one humectant is from the group comprising or consisting of lactic acid, glycerin, pyrrolidone carboxylic acid, sodium pyrrolidone carboxylic acid, dexpanthenol, 1,2-hexanediol, 1,2-heptanediol and a composition comprising or consisting of saccharide isomerate, water, citric acid and sodium citrate.

3. A composition according to claim 1 or 2, characterized in that the selective prebiotic composition comprises or consists of i. 5.0 to 15.0% (w / v) Xylitol, preferably 10.0 to 12.0% (w / v) Xylitol, ii. 24.0 to 34.0% (w / v), Anhydroxylitol, preferably 1,4-Anhydro- D-Xylitol preferably 28.0 to 32.0% (w / v) Anhydroxylitol, preferably 1,4-Anhydro-D- Xylitol, and iii. 35.0 to 50.0% (w / v) Xylitylglucoside, preferably 40.0 to 45.0% (w / v) Xylitylglucoside.

4. A composition according to any one or more of claims 1 - 3, characterized in that the composition has a pH from 3.8 to 5.5, preferably a pH from 3.8 to 4.5, 4.0 to 5.0, 4.4 to 5.5, 4.5 to 5.5 or 5.0 to 5.5, more preferably a pH from 4.0 to 5.5, most preferably a pH from pH 4.5 to pH 4.7, pH 4.5 to pH 5.5 or pH 4.4 to pH 5.5.BYH240210 FC -46- 5. A composition according to any one or more of claims 1 - 4, characterized in that the composition is free of strong detergents, preferably free of sodium lauryl sulfate and sodium laureth sulfates, free of volatile siloxanes, preferably free of octamethylcyclotetrasiloxane (D4), decamethylcyclopentasiloxane (D5) and dodecamethylcyclohexasiloxane (D6), and / or free of preservatives, preferably free of parabens, methylisothiazolinone and / or mineral oils.

6. A composition according to any one or more of claims 1 - 5 for use in the treatment and / or prevention of a skin disease, preferably for use in the treatment and / or prevention of an acne and / or an eczema skin disease, more preferably for use in the treatment and / or prevention of atopic dermatitis, contact dermatitis, dyshidrotic eczema and / or nummular eczema, most preferably for use in the treatment and / or prevention of atopic dermatitis, contact dermatitis, dyshidrotic eczema and / or nummular eczema in newborns, infants and / or children.

7. Non-therapeutic use of a composition according to any one or more of claims 1 - 5, characterized in that the composition is for strengthening the physical, biochemical and microbial layer of the skin, wherein the skin is newborn, infant, child, adolescent, adult or mature, preferably newborn and / or infant skin.

8. Topical use of a composition comprising:i. Xylitol,ii. Anhydroxylitol, preferably 1,4-Anhydro-D-xylitol, andiii. Xylitglucoside,as selective prebiotic, characterized in that the selective prebiotic has a selective bacteriostatic and / or selective prebiotic function.

9. Use according to claim 8, characterized in that the composition for topical use consists of:i. Xylitol,ii. Anhydroxylitol, preferably 1,4-Anhydro-D-xylitol,iii. Xylitylglucoside,iv. Water, andv. Glucose.

10. Use according to claim 8 or 9, characterized in that composition comprises:i. 5.0 to 15.0% (w / v) Xylitol, preferably 10.0 to 12.0% (w / v) Xylitol,BYH240210 FC -47- ii. 24.0 to 34.0% (w / v) Anhydroxylitol, preferably 24.0 to 34.0% (w / v) 1,4- Anhydro-D-xylitol, more preferably 28.0 to 32.0% (w / v) Anhydroxylitol, most preferably 28.0 to 32.0% (w / v) 1,4-Anhydro-D-xylitol, andiii. 35.0 to 50.0% (w / v) Xylitylglucoside, preferably 40.0 to 45.0% (w / v) Xylitylglucoside.

11. Use of a composition according to any one or more of claims 8 to 10, characterized in that the composition comprises or consists of:i. 5.0 to 15.0% (w / v) Xylitol, preferably 10.0 to 12.0% (w / v) Xylitol,ii. 24.0 to 34.0% (w / v) Anhydroxylitol, preferably 24.0 to 34.0% (w / v) 1,4- Anhydro-D-xylitol, more preferably 28.0 to 32.0% (w / v) Anhydroxylitol, most preferably 28.0 to 32.0% (w / v) 1,4-Anhydro-D-xylitol,iii. 35.0 to 50.0% (w / v) Xylitylglucoside, preferably 40.0 to 45.0% (w / v) Xylitylglucoside,iv. 12 to 20% (w / v) Water, preferably 15 to 17% (w / v) Water, andv. 0 to 5% (w / v) Glucose, preferably 1 to 4% (w / v) D-glucose.

12. Use according to any one or more of claims 8 - 11, characterized in that the composition is free of additional alditols.

13. Use according to any one or more of claims 8 - 12, characterized in that the selective prebiotic has a selective bacteriostatic and / or prebiotic function on skin microbiome.

14. Use according to any one or more of claims 8 - 13, characterized in that the composition is contacted with a microbiome comprising site for at least 0.5, 1, 2, 5, 10, 15, 30, 45, 60, 90, 120, 180, 240, 480, 720, 960, 1100, or 1440 minutes.

15. Use according to any one or more of claims 8 - 14, characterized in that the selective prebiotic supports the growth of beneficial bacteria Staphylococcus epidermidis and / or reduces the growth of pathogenic or opportunistic pathogenic bacteria Staphylococcus aureus and / or Cutibacterium acnes. and / or reduces the growth of commensal bacteria Corynebacterium striatum, preferably when beneficial bacteria are in growth competition with pathogenic and / or opportunistic pathogenic and / or commensal bacteria.

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