An oil-in-water emulsion composition for use as a topical moisturizing, Anti-itch, Anti-infectious and Anti-microbial composition

Abstract

The present invention relates to novel compositions for topical use.

Description

[0001] An oil-in-water emulsion composition

[0002] Field of the invention

[0003] The present invention relates to the field of cosmetics and skin care, in particular to a composition in the form of an oil-in-water emulsion, notably a cutaneous emulsion e.g. cream or lotion. The present invention also relates to the use of such a composition and a process for preparing it. In another aspect, present invention relates to a composition capable of suppressing or eliminating pathogenic microorganism to a higher degree as compared to commensal micro-organisms, thereby facilitating and supporting a healthy skin microbiota. Furthermore, present invention relates to prevention and treatment of e.g. dry skin, infected skin, or relates to prevention and treatment of pruritus.

[0004] Background of the invention

[0005] The skin is a multi-functional organ functioning as our primary environmental barrier. It protects us from mechanical impact, preventing dehydration, regulating body temperature and allow us to perceive the world around us through different nerve endings. In addition to the physical barrier, preventing us from invading pathogens, chemicals and allergens, skin cells can selectively respond to the presence of skin microbial pathogens to induce production of antimicrobial peptides.

[0006] Dry skin or xerosis is a frequent condition occurring at any age. Dry skin is triggered by hereditary factors, age-related decrease in intercellular lipids and natural moisturizing factors, such as free amino acids and specific salts in the stratum corneum. In addition, the disturbance of the skin barrier by extrinsic stimuli can also induce dry skin, including low environmental temperature, low humidity, chemical exposures and microorganisms.

[0007] The consequence of dry skin can include impairment in barrier function, inflammation and loss of suppleness leading to cracking of the skin. When the skin is extremely dry, excessive flaking of corneocytes can cause the formation of microfissures and an increase in mast cells and histamine levels, resulting in chronic pruritus i.e. itch.

[0008] Pruritus, often a consequence of dry skin, leads to scratching that further increases the inflammation and barrier impairment. This can also lead to infection from bacteria normally habiting the skin e.g. Staphylococcus aureus (S. aureus). S. aureus, a bacterial pathogen associated with itchy skin diseases, has been identified to induce itch by itself. S. aureus directly activates pruriceptor sensory neurons to drive itch, causing scratch-induced skin damage. [Deng L. et. al. Cell 186, 5375-5393, 2023],

[0009] Skin infections, irritation, pruritus, xerosis and other skin ailments are widespread and a major problem to many. Skin diseases affect at least 25% of the population in the United States, with skin infections accounting for the largest burden. Skin abnormalities can lead to sensitive and vulnerable skin. Periods of sensitive and vulnerable skin can also occur after skin injuries such as cuts, abrasions, cracks, burns etc.

[0010] The entire skin with its different conditions regarding dryness, humidity and sebaceous concentration is inhabited by microbial communities, including bacteria, fungi, viruses and microeukaryotes, i.e. the skin microbiome.

[0011] A healthy microbiome constitutes of commensal microbes that provides protection against potential invasion of pathogens by both indirect, competitive exclusion, and direct action, i.e. biosynthesis of microbiome derived antimicrobial substances.

[0012] Skin commensals are defined as microorganisms whose interaction on the skin are either beneficial or neutral.

[0013] Normalization of a disturbed skin microbiome together with strengthening the skin barrier by moisturizing dry skin is essential in dermal treatment.

[0014] Dry skin together with itch and scratch-induced skin damage, where the barrier is compromised, are often complicated by secondary, usually bacterial, infections which optimally is to be avoided.

[0015] Lowering the risk of an entry point for infections in the skin, by softening and moisturizing of the skin, can prevent these skin infections. After a skin disease, the skin is often still vulnerable and further treatment might be needed. Post-dermatological treatment and softening of the skin and reducing or impeding itch can be performed to obtain an optimal effect on the skin, without the use of a therapeutic compound. This can prevent further skin eruptions / irritations, which can lead to faster healing and thereby decrease the risk of other skin infections and diseases. In addition, by reducing skin microbial pathogens, in particular S. aureus the risk of itch and scratch damage to the skin is reduced together with the risk of secondary skin infections.

[0016] Moisturizers are a major component of basic daily skin care, particularly in presence of epidermal barrier alteration and reduced epidermal water content. It is an important strategy to maintain skin health as well as treating various dermatoses which co-exist with skin dryness and are linked to impaired skin barrier function. Moisturizers improve skin barrier repair, maintain skin’s integrity and appearance by acting as humectants, emollients, and occlusives, each with its own mechanism of action.

[0017] Humectants consist of hygroscopic substances helping the stratum corneum to absorb water by attracting water from dermis and a humid environment into the epidermis. Honey, sorbitol, glycerin, panthenol, urea, gelatin, hyaluronic acid, alpha hydroxy carboxylic acids (glycolic acid, lactic acid, sodium pyrrolidine carboxylic acid), propylene glycol and butylene glycol are some examples of humectants.

[0018] Even if many different products are on the market, there is still a need for improved compositions. It is an object of the invention to provide a composition that can be easily applied to the skin and which composition easily integrates with the skin and leaves the skin soft, smooth and elastic. The composition should ideally include all the three important properties, i.e. humectant, emollient, and occlusive qualities.

[0019] In addition, the composition should ideally display skin microbiome normalizing properties where, specifically the pathogen S. aureus should be reduced to a higher degree as compared to commensals such as e.g. Staphylococcus epidermidis (S. epidermidis) in order to prevent and reduce itch and scratch-induced skin damage.

[0020] Moreover, in relation to skin related infections, there is a need for eliminating or suppressing microorganisms capable of causing skin infections or inflammations. Alternatively, there is also a need for a composition capable of maintaining the healthy natural flora of microorganisms which also entails reducing or preventing a microorganism to become invasive. Preferably, the composition according to the invention should eliminate or suppress microorganisms capable of causing skin infections, pruritis and inflammations, while at the same time maintain the healthy natural flora of microorganisms which also entails reducing or preventing a microorganism to become invasive. Moreover, the composition should provide the beneficial effects to the skin and at the same time be without or with a minimum content of additive ingredients that normally are regarded as unsuitable for use in subjects that suffers from sensitive skin, dry skin and allergic dermal diseases or conditions. Such additive substances are normally found among preservatives, perfumes, coloring agents and the like.

[0021] In the art, EP 0719137 may be mentioned. The documents relate to in form of a W / O or O / W emulsion comprising an amphoteric surfactant solution comprising one or more alkylated or ethylated betaine moiety in combination with one or more alkylated or acylated amine oxide moiety. Moieties of alkylated betaines and amine oxides have known antimicrobial properties. An equimolar mixture of N-alkyl betaine and N-alkyl-N,N dimethylamine oxide was patented in 1978 in a compound called C31G, with chain lengths ranging from C8 to C18 and buffered in a citrate buffer. C31G was first shown to have pronounced wound healing and deodorizing effects, as well as antimicrobial sensitivity. Further studies showed that C31G exhibited pronounced activity not only against bacteria, but also against yeasts, fungi, sperm, and enveloped viruses. Both moieties carry a positive charge at pH typically below neutral. Both acts predominantly on gram-positive bacteria such as e.g. s. aureus and s. epidermidis, due to direct interaction with exposed peptidoglycan cell walls. The antimicrobial moieties disclosed in the compositions do not display any discriminatory effect on commensal to pathogenic microorganisms and is considered to be generally antiseptic compositions.

[0022] Herman. A, Current Mircobiology, 2019, 76, pp. 744-754, relates to compositions comprising various antimicrobial properties of different alcohols and investigations on the anti-microbial property thereof. However, no distinction is demonstrated or observed regarding selectivity for pathogenic microorganisms over commensals.

[0023] Deen, A., et al., J Sci Food Agric, 2021 , 101 , pp. 2182-2193, relates to health benefits of different orally administered coconut oils. However, no distinction is demonstrated or observed regarding selectivity for pathogenic microorganisms over commensals and no such effects are discussed.

[0024] Consequently, none of the above prior art describes the inventive effort of present invention and in particular, none of the above mentioned documents discuss any topical compositions wherein non-pathogenic / commensal microorganisms are affected to a lesser degree than pathogenic microorganisms or that any compositions would be capable of displaying any selectivity between said two different types of microorganisms.

[0025] Summary of the invention

[0026] In one aspect the present invention provides a composition comprising

[0027] - an oil phase from about 10%w / w to about 25%w / w of the total composition, wherein the oil phase comprises i) at least one oil having a content of at least 80%w / w saturated fatty acids and wherein the total of said at least one oil makes up at least 35%w / w of the oil phase, and ii) at least one emulsifying agent, and

[0028] - an aqueous phase from about 75%w / w to about 90%w / w of the total composition, wherein the aqueous phase comprises at least one alkylene glycol, and wherein said at least one alkylene glycol makes up at least about 29%w / w of the aqueous phase.

[0029] In one embodiment of the invention the at least one alkylene glycol in the composition may be propylene glycol.

[0030] In another aspect, the alkylene glycol may be e.g. one or more of e.g. propylene glycol, butylene glycol, pentylene glycol, hexylene glycol or mixtures thereof.

[0031] In another embodiment of the invention the at least one oil in the composition may be e.g. coconut oil.

[0032] In another embodiment of the invention the composition has a weight ratio between the at least one alkylene glycol and water may be from e.g. about 1 : 1 to e.g. about 1 : 3.

[0033] In yet another embodiment of the invention the composition has a weight ratio between the at least one alkylene glycol and the at least one oil contained in the composition which is from e.g. about 1 :1 to e.g. about 5: 1.

[0034] In yet another embodiment of the invention the composition may comprise about 21 to about 40 %w / w of propylene glycol, about 5 to about 15%w / w of a vegetable oil, about 1 to about 10%w / w of one or more emulsifying agents, optionally about 0.1 to about 1 %w / w of one or more buffering agents, about 0.2% w / w to about 7% w / w of one or more viscosity increasing agents. Ad up to 100%w / w with water. In another aspect, the composition according to the invention may optionally comprise a non-cyclic silicone oil as an occlusive agent in an amount up to about 2%w / w.

[0035] In yet a further aspect, the composition according to the invention may optionally comprise a trihydroxy alcohol as a humectant in a concentration up to about 4%w / w.

[0036] The composition according to the present invention has excellent emollient, softening and moisturizing effects. The composition is easy to apply as the continuous phase is aqueous. Further, the composition of the invention includes the three important qualities i.e. humectant, emollient, and occlusive properties.

[0037] It is furthermore illustrated that the composition of the invention has antimicrobial properties. It has surprisingly been found that the humectant propylene glycol may be added in concentration of about above 12.5% w / w in order to reduce the skin pathogen S. aureus. It has also been surprisingly found that the humectant propylene glycol may be added in a concentration above 20%w / w in order to avoid the addition of preservatives in the self-preserved composition. In another aspect, the alkylene glycol may be present in an amount of e.g. about 21%w / w to about 40%w / w, such as e.g. from about 21%w / w to about 30%w / w, or e.g. from about 23%w / w to about 27%w / w.

[0038] In another aspect the present invention therefore provides a composition for use as an antimicrobial composition, such as for the use in a method for the treatment of skin infections.

[0039] In one aspect, present invention relates to a cutaneous o / w emulsion composition for use as an anti-infectious and / or anti-microbial composition for administration on the skin, comprising an oil phase from about 10%w / w to about 25%w / w of the total composition, wherein the oil phase comprises i) at least one oil each having a content of at least 80%w / w saturated fatty acids and wherein the total of said at least one oil makes up at least 35%w / w of the oil phase, and ii) at least one emulsifying agent, and an aqueous phase from about 75%w / w to about 90%w / w of the total composition, wherein the aqueous phase comprises at least one alkylene glycol selected from propylene glycol, butylene glycol, pentylene glycol, hexylene glycol or mixtures thereof, and wherein said at least one alkylene glycol makes up at least about 29%w / w of the aqueous phase, whereby pathogenic microorganisms are reduced to a higher extent as compared to the commensal microbiota or microorganisms.

[0040] In a further aspect, the present invention therefore provides a composition for use as an antipruritic composition, such as for the use in a method for the treatment of pruritus.

[0041] Thus, in one aspect present invention relates to a cutaneous o / w emulsion composition for use as an anti-itch composition for administration on the skin, comprising an oil phase from about 10%w / w to about 25%w / w of the total composition, wherein the oil phase comprises i) at least one oil each having a content of at least 80%w / w saturated fatty acids and wherein the total of said at least one oil makes up at least 35%w / w of the oil phase, and ii) at least one emulsifying agent, and an aqueous phase from about 75%w / w to about 90%w / w of the total composition, wherein the aqueous phase comprises at least one alkylene glycol selected from propylene glycol, butylene glycol, pentylene glycol, hexylene glycol or mixtures thereof, and wherein said at least one alkylene glycol makes up at least about 29%w / w of the aqueous phase, whereby pathogenic microorganisms are reduced to a higher extent as compared to the commensal microbiota or microorganisms.

[0042] In yet a further aspect, the present invention provides for a composition capable of maintaining a healthy skin microbiota, including the commensals. The composition according to the invention is capable of reducing the pathogen S. aureus to a higher degree as compared to the commensals, such as e.g. S. epidermidis.

[0043] Consequently, the present invention relates to the use of the composition disclosed herein for the prevention and treatment of skin infections and pruritus, whereby the composition serves to suppress harmful bacteria, such as e.g. S. aureus, while at the same time reducing the impact on the healthy natural flora of microorganisms on the skin.

[0044] In a further aspect the present invention provides a composition for use as an antixe- rotic composition, such as for the use in a method for the treatment of dry skin.

[0045] Thus, present invention relates to a cutaneous o / w emulsion composition for use as a topical moisturizing composition for administration on the skin, comprising an oil phase from about 10%w / w to about 25%w / w of the total composition, wherein the oil phase comprises i) at least one oil each having a content of at least 80%w / w saturated fatty acids and wherein the total of said at least one oil makes up at least 35%w / w of the oil phase, and ii) at least one emulsifying agent, and an aqueous phase from about 75%w / w to about 90%w / w of the total composition, wherein the aqueous phase comprises at least one alkylene glycol selected from propylene glycol, butylene glycol, pentylene glycol, hexylene glycol or mixtures thereof, and wherein said at least one alkylene glycol makes up at least about 29%w / w of the aqueous phase, whereby pathogenic microorganisms are reduced to a higher extent as compared to the commensal microbiota or microorganisms.

[0046] In a further aspect the present invention provides a process for preparing the composition according to the invention, comprising the steps: i) preparing the oil phase by mixing the ingredients that make up the oil phase and heating to a temperature of from 60 °C to 80 °C, notably from 65 °C to 75 °C such as about 70 °C, ii) preparing the aqueous phase by dissolving the ingredients that make up the aqueous phase, optionally by heating to 55 °C to 75 °C, notably from 60 °C to 70 °C such as about 65 °C, iii) mixing the oil phase i) and the aqueous phase ii) until an emulsion is obtained, iv) optionally, subjecting the thus obtained emulsion to vacuum conditions, v) optionally, homogenizing the emulsion optionally under vacuum conditions, vi) optionally, addition of one or more fragrance agents, vii) cooling the thus obtained emulsion.

[0047] Brief description of the figures

[0048] Figure 1 illustrates the inhibition of S. aureus in cutaneous emulsion according to example 21 (including 25% w / w propylene glycol), solid line and Example 22, (including 20% w / w propylene glycol), dashed line.

[0049] Figure 2 illustrates the Inhibition of P. aeruginosa in cutaneous emulsion according to example 21 (including 25% w / w propylene glycol), solid line and Example 22, (including 20% w / w propylene glycol), dashed line. Figure 3 illustrates the inhibition of C. albicans in cutaneous emulsion according to example 21 (including 25% w / w propylene glycol), solid line and Example 22, (including 20% w / w propylene glycol), dashed line.

[0050] Figure 4 illustrates the Inhibition of Aspergillus niger'm cutaneous emulsion according to example 21 (including 25% w / w propylene glycol), solid line and Example 22, (including 20% w / w propylene glycol), dashed line. X-axis represents time in days and y- axis represents viable count of A niger'm CFU.

[0051] Figure 5 illustrates the growth of S aureus over time in bacterial suspensions with the concentration of about 105CFU / mL. Each well contained 100 pL of inoculum and 100 pL of MH broth of pH 7.4 with 12,5% v / v propylene glycol and without propylene glycol. After incubation absorbance was recorded at 600 nm.

[0052] Figure 6 illustrates the growth of S aureus over time in bacterial suspensions with the concentration of about 105CFU / mL. Each well contained 100 pL of inoculum and 100 pL of MH broth of pH 5.0 with 12,5% v / v propylene glycol and without propylene glycol. After incubation absorbance was recorded at 600 nm.

[0053] Figure 7 illustrates the growth of S epidermidis over time in bacterial suspensions with the concentration of about 105CFU / mL. Each well contained 100 pL of inoculum and 100 pL of MH broth of pH 7.4 with 12.5% v / v propylene glycol and without propylene glycol. After incubation absorbance was recorded at 600 nm.

[0054] Figure 8 illustrates the growth of S epidermidis over time in bacterial suspensions with the concentration of about 105CFU / mL. Each well contained 100 pL of inoculum and 100 pL of MH broth of pH 5.0 with 12.5% v / v propylene glycol and without propylene glycol. After incubation absorbance was recorded at 600 nm.

[0055] Figure 9 illustrates photographs of agar plates grown with S. aureus and S. epidermidis (1 :1) at pH 5.0, plated after 0, 24 and 48 hours of incubation in MH broth with and without 12.5% propylene glycol. Upper three plates incubated without propylene glycol.

[0056] Lower three plates incubated with 12.5% propylene glycol in MH broth. S. aureus is identified by yellow colonies and S. epidermidis by white colonies. Figure 10 illustrates skin hydration from different humectants incorporated in the same base formulation. The used humectant concentrations are relevant from existing commercial products. Conductance results, in pS, are the difference from measured conductance minus blank conductance and the mean from one left and right arm.

[0057] Detailed description of the invention

[0058] The present invention provides a composition, notably cosmetic compositions as no pharmaceutically active drug substance is included. The composition is in the form of an oil-in-water emulsion. A composition according to the invention may contain two phases, an aqueous phase, which is the continuous phase and an oil phase, which is the disperse phase that is homogeneously distributed in the continuous phase (i.e. as generally seen in o / w emulsions). The invention specifically relates to an elegant topical formulation for softening and moisturizing the skin. The oil-in-water formulation makes it suitable for topical use, as it is easy to apply to the skin.

[0059] The composition of the invention comprises:

[0060] - an oil phase from about 10%w / w to about 25%w / w of the total composition, wherein the oil phase comprises i) at least one oil having a content of at least 80%w / w saturated fatty acids and wherein the total of said at least one oil makes up at least 35%w / w of the oil phase, and ii) at least one emulsifying agent, and

[0061] - an aqueous phase from about 75%w / w to about 90%w / w of the total composition, wherein the aqueous phase comprises at least one alkylene glycol selected from propylene glycol, butylene glycol, pentylene glycol, hexylene glycol or mixtures thereof, and wherein said at least one alkylene glycol makes up at least about 29%w / w of the aqueous phase.

[0062] It is important to note that the composition preferably does not include normally employed preservatives or traditional anti-microbial agents. The reason being that the components of the composition itself contains a sufficient amount of alkylene glycol to obtain an adequate preservation effect of the product. This has been confirmed in challenge tests according to Ph. Eur. “Tests for Efficacy of Antimicrobial Preservation”. The composition of the present o / w emulsion invention comprising propylene glycol has shown to satisfy the criteria for cutaneous preparations in Ph. Eur. 5.1.3. Hence, the composition is self-preserved and has sufficient antimicrobial properties for product stability. In one aspect, the concentration of e.g. propylene glycol may be about 21 % w / w or above.

[0063] More specifically, the present invention provides a composition comprising at least one alkylene glycol selected from propylene glycol, butylene glycol, pentylene glycol, hexylene glycol or mixtures thereof. The concentration of the at least one alkylene glycol selected from propylene glycol, butylene glycol, pentylene glycol, hexylene glycol or mixtures thereof in the aqueous phase of the composition is at least about 29%w / w. Hence the concentration of the at least one alkylene glycol selected from propylene glycol, butylene glycol, pentylene glycol, hexylene glycol or mixtures thereof in the composition is typically from about 21%w / w to 40%w / w.

[0064] The upper limit is set to avoid unnecessary irritation of the skin, and the lower limit is set to ensure i) a suitable antiseptic, ii) a suitable antimicrobial effect, and / or iii) a suitable humectant effect. As appears from the examples herein, the use of propylene glycol is preferred, but it is contemplated that other alkane-diols as well may be used in combination with propylene glycol (1 ,2-propane-diol), such as propylene glycol (1 ,3-pro- pane-diol), butylene glycol (1 ,3-butane-diol), pentylene glycol (1 ,5-pentane-diol), and / or hexylene glycol (1-methyl-2,4-pentane-diol). When propylene glycol, butylene glycol, pentylene glycol or hexylene glycol is used in any combination, the total concentration of the “glycols” is as mentioned above.

[0065] In order to achieve a desired antiseptic or anti-microbial effect it is important to balance the content of water and the content of the alkylene glycol. It is well-known that water is a good growth medium for microorganisms and, accordingly, an increase in water content will increase the risk of contamination or microbial growth. Hence, the weight ratio between alkylene glycol and water in the composition is believed to be important in order to achieve a good balance between product properties when applied to the skin and product stability during storage and / or in-use.

[0066] A suitable weight ratio between alkylene glycol and water is from about 1 :1 to about 1 :3. The weight ratio is normally from about 1 :1.4 to about 1 :2.8 such as from about 1 :1.7 to about 1 :2.5 or from 1 :2.0 to 1 :2.3. As mentioned above, the use of propylene glycol as alkylene glycol in a composition of the invention has shown to possess the desired properties, both humectant and antimicrobial. In the examples a suitable ratio is found to be about 1 :2.0 to 1 :2.3 when e.g. about 25%w / w propylene glycol is employed.

[0067] In one embodiment the composition has a concentration of propylene glycol from about 21 %w / w to about 40%w / w such as from about 21 %w / w to about 30%w / w, or from about 23%w / w to about 27%w / w.

[0068] In another embodiment the composition has a concentration of propylene glycol from about 21 %w / w to about 40%w / w.

[0069] In one embodiment, the composition has a concentration of propylene glycol from about 21 %w / w to about 30%w / w.

[0070] In one embodiment, the composition has a concentration of propylene glycol from about 23%w / w to about 27%w / w.

[0071] In another embodiment of the composition, the at least one alkylene glycol is propylene glycol and the concentration of propylene glycol in the composition is about 25%w / w, the at least one oil is coconut oil and the concentration of coconut oil in the composition is about 5% w / w to 15% w / w, or from about 6% w / w to 12% w / w.

[0072] As mentioned above, an emulsion is established by mixing an aqueous phase and an oil phase. In an oil-in-water emulsion, the oil is present in droplets homogeneously dispersed in the aqueous phase. In order to stabilize the emulsion against phase separation, surface active agents or emulsifying agents are added.

[0073] In a composition of the present invention, at least 35% w / w of the oil phase comprises an oil selected from a group consisting of oils that have a content of saturated fatty acids of at least 80% w / w. Such oils include vegetable oils like coconut oil, cottonseed oil, and palm oil. The selected oil should additionally have a suitable melting point in order to show good cosmetic properties i.e. spreadability on the skin. Suitable oils start to melt at about 10°C to 30°C. Cotton seed oil starts to melt at about 10°C, coconut oil at about 23°C and palm oil at around 30°C. An advantage of using a highly saturated oil is that it is less prone to degradation, i.e. the composition has a shelf-life of at least 2 years when stored at 25°C and 60% RH.

[0074] The combined use of a highly saturated oil and an alkylene glycol is important to achieve the desired effect on the skin. The content of oil is important as it stays on the skin for a prolonged period of time, whereby it contributes to the occlusive effect and thereby improving the barrier of the skin against the environment and contributes to the regeneration or repair of the skin; the content of water is important as it ensures an even and easy distribution of the composition on the skin and it ensures incorporation of the composition into the skin layer (stratum corneum and / or epidermis); and finally the content of an alkylene glycol is important as it has the same function as water, besides its antimicrobial properties, and in addition it is also acts as a humectant and stays longer on / in the skin than water.

[0075] The remaining part of the oil phase may be made up by other natural oils and fats, mineral oils, ester oils, silicon oils or waxes, or other fat-soluble substances like e.g. surfactants. Notably, such other oil / fat is a vegetable oil / fat such as avocado oil, corn oil, linseed oil, grape seed oil, hemp seed oil, peanut oil, safflower oil, soybean oil, olive oil, sunflower oil and canola oil etc. Fats can be defined as bulk storage material produced by plants, animals and microorganisms that contain aliphatic moieties, such as fatty acid derivatives. These are mainly, but not entirely, mixtures of triglycerols (triglycerides) and are known as oils or fats depending on whether they are liquid or solid at room temperature. In the present context, the term “oil” also includes “fat” and oil / fat may also be produced synthetically or semi-synthetically.

[0076] The total concentration of the oil / fat in a composition of the invention is from about 5%w / w to about 30%w / w, such as from about 8%w / w to about 25%w / w or from 10% w / w to 20% w / w.

[0077] The emulsion has an exceptional softening effect on the skin, potentially due to the specific combination of propylene glycol (or another alkylene glycol as mentioned above) and oil in the emulsion. It is contemplated that propylene glycol or another glycol, if present, binds water, as a humectant, leading to an improved softening, emollient and moisturizing effect compared to an emulsion without propylene glycol (or another alkylene glycol as mentioned above). A suitable weight ratio between the alkylene glycol and oil is from about 1 :1 to about 5: 1. Thus, the weight ratio is normally from 1.5:1 to about 4.8: 1 : such as from about 1.8:1 to about 4.5:1 or from 2.0:1 to 4.2:1.

[0078] The above weight ratio between the oil and the alkylene glycol in the composition is also valid when the weight ratio is calculated between the content of oil having at least 80%w / w content of saturated fatty acids and the alkylene glycol.

[0079] As mentioned above, stabilization of the composition according to the invention is achieved by the emulsifying agents. An emulsion of the present invention may therefore comprise at least two emulsifying agents having a Hydrophilic-Lipophilic Balance (HLB) in the range from about 3 to about 20.

[0080] The emulsifying agents typically “bind” the aqueous and the oil phases together in the emulsion and, accordingly, the emulsifying agents are localized near the interface between the aqueous phase and the oil phase where they form stabilizing structures. In the present context, emulsifying agents with a HLB value from 11-20 are more water soluble whereas emulsifying agents with a HLB value from 3 and up to 11 , but not including 11 are more oil soluble.

[0081] As seen from the example herein the use of three emulsifying agents having a HLB (hydrophilic-lipophilic balance) in the range 3-20, one with a high HLB, i.e. a HLB from about 11 - 20 and two with a low HLB, i.e. a HLB from about 3 - 11 , gives the desired result with respect to stability.

[0082] Suitable emulsifying agents for use in a composition of the invention may be selected from the group consisting of glycerol alkyl esters, macrogol alkyl esters, polyoxyethyleneglycol alkyl esters, fatty acids, polyoxyethylene sorbitan esters, polyoxyethylene alkyl ethers and galactolipids.

[0083] The concentration of the emulsifiers in the composition according to the present invention ranges from about 1 % w / w to about 10% w / w or about 4 - 8% w / w. The concentration of each emulsifier when present in a composition according to the present invention ranges from about 0.3 %w / w to about 5%w / w. In one embodiment the composition of the invention contains three emulsifying agents, such as two emulsifying agents having a HLB from 3-11 and one emulsifying agent having a HLB from 11-20.

[0084] In another embodiment the composition of the invention has the one or more emulsifying agents consisting of glycerol monostearate 40-55, macrogol stearate and stearic acid.

[0085] In another embodiment of the invention the composition has the one or more emulsifying agents consisting of glycerol monostearate 40-55, macrogol stearate and stearic acid, wherein the concentration ratio in the composition between glycerol monostearate 40-55, macrogol stearate and stearic acid is about 6:6:1 , such as the concentrations in the composition being about 3%w / w, about 3%w / w and about 0.5%w / w of the total composition, respectively.

[0086] In another embodiment of the invention the composition has the one or more emulsifying agents consisting of glycerol monostearate 40-55, macrogol stearate and stearic acid, wherein the concentration ratio in the composition between glycerol monostearate 40-55, macrogol stearate and stearic acid is about 10:10:3, such as the concentrations in the composition being about 3% w / w, about 3% w / w and about 0.9% w / w of the total composition, respectively.

[0087] In another embodiment of the invention the composition has the one or more emulsifying agents consisting of glycerol monostearate 40-55, macrogol stearate and stearic acid, wherein the concentration ratio in the composition between glycerol monostearate 40-55, macrogol stearate and stearic acid is about 3:3:2, such as the concentrations in the composition being about 3% w / w, about 3% w / w and about 2% w / w of the total composition, respectively. Moreover, a composition according to the invention may comprise a viscosity-increasing agent. Viscosity-increasing agents suitable for use in the composition may be selected from the group consisting of fatty alcohols. The concentration of the viscosity-in- creasing agent is typically from about 0.5%w / w to about 7%w / w of the total composition. Preferred viscosity-increasing agents are saturated fatty alcohols having from 14 to 20 carbon atoms and mixtures thereof. Examples include myristyl alcohol (14 carbon atoms), pentadecyl alcohol (15 carbon atoms), cetyl alcohol (16 carbon atoms), heptadecyl alcohol (17 carbon atoms), stearyl alcohol (18 carbon atoms), nonadecyl alcohol (19 carbon atoms) and arachidyl alcohol (20 carbon atoms), and mixtures thereof such as eg cetostearyl alcohol (fatty alcohol containing a mixture of fatty alcohols with 16 and 18 carbon atoms). Unsaturated fatty alcohols should be avoided in order to avoid undesired oxidative degradation. The concentration normally dependents on the specific type of fatty alcohol used and a person skilled in the art will know how to adjust the concentration of such specific concentrations to obtain the desired viscosity.

[0088] As seen from the examples herein, a suitable viscosity-increasing agent is cetostearyl alcohol. In general, the concentration of the viscosity-increasing agent in the form of a fatty alcohol ranges from about 0.5%w / w to about 7%w / w based on the total composition.

[0089] The fatty alcohols can optionally be combined or replaced with a polymer, preferably a biodegradable polymer. The concentration of the polymer is typically up to about 1% w / w in a cutaneous emulsion and the total amount of one or more viscosity increasing agents is from about 0.2% w / w to about 7% w / w.

[0090] Biodegradable polymers are a special class of polymer that breaks down after its intended purpose by bacterial decomposition process to result in natural byproducts such as gases (CO2, N2), water, biomass, and inorganic salts e.g. cellulose derivatives and polysaccharides.

[0091] Examples of cellulose derivatives are hydroxypropyl cellulose and hydroxypropylmethyl cellulose (hypromellose) and example of polysaccharides are alginate, xanthan and carrageenan. If present, such viscosity increasing agent is part of the aqueous phase.

[0092] In general, the concentration of the viscosity increasing agents in the form of biodegradable polymers, e.g. hypromellose, ranges from 0.1 - 0.8% w / w based on the total composition. The composition may further contain a non-cyclic silicone oil e.g. dimeticone in a concentration of up to about 2% w / w. Silicon oils have beneficial cosmetic properties due to their low surface tensions, resulting in smooth spreading in addition to their emollient and occlusive properties.

[0093] The composition of the invention is mainly intended for topical use, i.e. as a cutaneous emulsion to apply on the skin. Accordingly, pH should be adjusted to a skin-friendly pH. A suitable pH is below 6 such as from about 3 to about 6 or from about 4.0 to about 6.0 or from about 4.0 to about 5.5. The pH may be adjusted by use of one or more pH ad- justing / buffering agent, which may be selected from the group consisting of e.g. hydrochloric acid, phosphoric acid, sodium hydroxide, citrate buffer, phosphate buffer, phthalate buffers, acetate buffers, succinate buffers. In order to arrive at a pH below 6 or about 4.5 to about 5.5, a citrate buffer has proved to be suitable. If present, one or more such pH adjusting agents are part of the aqueous phase and the total concentration is typically from about 0.1% w / w to about 1% w / w.

[0094] Thus, according to one aspect, the composition according to the invention may have a pH from about 4.5 to about 5.5, such as e.g. about 5.0.

[0095] The composition of the invention may further optionally comprise a humectant, besides the alkylene glycol, e.g. glycerol. Typically, the concentration of glycerol in the composition is from about 0.1%w / w to about 10%w / w or about 3% w / w to 7% w / w, if used. In one embodiment the concentration of the glycerol in the composition is about 4%w / w.

[0096] The present invention also provides a process for manufacturing the composition of the invention. The procedure is detailed described in Example 24 and a person skilled in the art will understand that the individual ingredients mentioned can be replaced by the ingredients mentioned in Table 8 below having the same functionality and in the concentration ranges mentioned.

[0097] More specifically, the process comprises i) preparing the oil phase by mixing the ingredients that make up the oil phase and heating to a temperature of from 60 °C to 80 °C, notably from 65 °C to 75 °C such as about 70 °C, ii) preparing the aqueous phase by dissolving the ingredients, optionally by heating to 55 °C to 75 °C, notably from 60 °C to 70 °C such as about 65 °C. iii) transferring the oil phase i) to the aqueous phase ii) or optionally ii) to i) iv) mixing until an emulsion is obtained, v) optionally, subjecting the thus obtained emulsion to vacuum conditions, vi) optionally, homogenizing the emulsion optionally under vacuum conditions, vii) optionally, addition of one or more fragrance agents, viii) cooling the thus obtained emulsion.

[0098] The ingredients, included in the oil phase i) above, are typically an oil as described herein and all the ingredients that are soluble in the oil phase. Such ingredients may be one or more emulsifying agents, one or more viscosity-increasing agents, optionally one or more fragrance agents or the like. If present, depending on the solubility in the oil phase, the non-cyclic silicon oil is either dissolved or dispersed in the oil phase. The ingredients included in the aqueous phase ii) is water and ingredients that are soluble in water such as e.g. propylene glycol and, optionally one or more C3-C6 alkane-diols, one or more pH regulating agents, if present, one or more polymer acting as viscosityincreasing agents, one or more humectant, if present and the like.

[0099] The composition of the present invention is typically a cosmetic composition, such as a cutaneous emulsion. In one embodiment the composition of the invention is a cream and in another embodiment the composition of the invention is a lotion.

[0100] In one embodiment the composition of the invention is for use as an antimicrobial composition.

[0101] In yet another embodiment, the composition of the invention is for use as an antimicrobial cutaneous emulsion for application onto infected skin.

[0102] Hence, the composition may be used for the treatment of infected skin, such as applying the composition to the skin area having infection once daily for a period of at least 14 days, at least 30 days or at least 60 days. Alternatively, the composition is applied to the skin area having infection twice or thrice daily for a period of at least 14 days, at least 30 days or at least 60 days.

[0103] In another embodiment the composition is for use as an antipruritic composition or an anti-itch composition. Hence, the composition may be used in a method for the treatment of pruritus. In yet another embodiment the use of the composition of the invention is for the application to a dry skin area to obtain a skin barrier strengthening and a long softening effect. In a specific embodiment the composition is used for the application to a dry skin area to obtain a long softening effect while strengthening and restoring the normal skin barrier function.

[0104] In yet a further embodiment the use of the invention is for the prevention of dry skin, impaired skin barrier, pruritis and skin infection.

[0105] In a further embodiment the composition of the invention has a stability of at least 24 months when stored at 25 °C, stored in a suitable primary packaging, wherein the stability is assessed by quantifying the physical stability, viscosity and pH, and product microbial quality.

[0106] In one particular embodiment, the composition is for use as an antimicrobial composition while at the same time maintaining the naturally occurring non-pathogenic microbiota of the skin. Specifically, the use according to this particular aspect, provides for a higher antimicrobial effect against pathogenic microorganisms while the effect is lower when considering non-pathogenic microorganisms. Examples of pathogenic microorganisms may be species of genus Streptococcus or species of genus Staphylococcus. Non-limiting examples may be e.g. Group A Streptococcus and S. aureus. Other microorganisms may be e.g. fungal microorganisms such as e.g. Malassezia spp.

[0107] On the skin, normally Staphylococcus spp., Micrococcus spp., Corynebacterium spp., Rhodococcus, Propionibacterium spp., Brevi bacterium, Dermabacter, and Acietobacter may be found. These are usually called either commensals or mutualistic.

[0108] Of the pathogenic bacteria, and as mentioned above, e.g. S. aureus is usually pathogenic which is also valid for Pseudomonas aeruginosa and Streptococcus pyogenes and these may thus be regarded as pathogenic microorganisms. Present invention primarily targets microorganisms usually considered pathogenic.

[0109] In a particular aspect, present invention relates to targeting S. aureus and consequently aims at selectively inhibit S. aureus while at the same time affecting the commensals or mutualistic skin flora or microorganisms to a lesser extent. Consequently, present invention relates, in one aspect, to the use of the composition according to the invention for reducing and / or eliminating pathogenic microorganisms on the skin, while maintaining commensal or mutual microorganisms on the skin. As illustrated herein, the invention is exemplified by S. aureus and S. epidermis in a nonlimiting context and as a model differing between pathogenic and mutual / commensal microorganisms respectively.

[0110] In one aspect , the reduction may be measured by comparing the CFU (colony forming units) per ml.

[0111] Optimal reduction of the pathogenic microorganisms may be observed at typical pH of the skin, such as e.g. about pH 5.0.

[0112] In one aspect, in the presence of 12.5% PG (propylene glycol) and pH 5, S. epider- midis significantly dominates in the co-culture after 48 h of incubation, according to Figure 9. The viable cell count of S. epidermidis was -1000 cfu / mL, whereas S. aureus just -10 cfu / mL.

[0113] For both times, 24 h and 48 h the growth suppression was a factor of approximately 100 times lower for S. epidermidis as compared to S. aureus, illustrated according to Figure 6 and Figure 8.

[0114] The reduction of the commensal or mutual microorganisms may be observed at typical pH of the skin, such as e.g. about pH 5.0.

[0115] With respect to reduction of e.g. pathogenic microorganisms, the reduction thereof may be observed at about 24 h after application of the composition according to present invention, or about 48 h after application of the composition of present invention. The reduction thereof may increase over time. The lesser reduction of the commensal or mutual microorganisms may also be observed at about 24 h after application of the composition according to present invention, or about 48 h after application of the composition of present invention and may be such that the degree of impact of the composition of present invention is lower than the impact of the pathogenic microorganisms. In one aspect, by use of the composition according to present invention, the pathogenic microorganisms are reduced by about 1.5 times more than the commensal or mutual microorganisms on the skin (counted as CFU / ml), or about 2 times more, or about 2,5 times more, or about 3 times more, or about 4 times more, or about 5 times more, or about 6 times more, or about 7 times more, or about 8 times more, or about 9 times more, or about 10 more, or about 20 times more, about 50 times more, about 75 times more, about 100 times or more etc. than the commensal or mutual microorganisms on the skin. The reduction of the respective microorganisms may be observed after e.g. about 24 hours or about 48 h etc.

[0116] Thus, in one aspect, the composition according to the invention the MIC-value (minimum inhibitory concentration) is higher for the commensal or mutual microorganisms and lower for the pathogenic microbes.

[0117] In a particular aspect, the MIC value for the composition according to the invention may be 1.5 times higher for the commensal or mutual microorganisms on the skin, or about 2 times higher or more, or about 2,5 times higher or more, or about 3 times higher or more, or about 4 times higher or more, or about 5 times higher or more, or about 6 times higher or more, or about 7 times higher or more, or about 8 times higher or more, or about 9 times higher or more, or about 10 higher or more, or about 20 times higher or more, about 50 times higher or more, about 75 times higher or more, about 100 times higher or more, about 200 times higher or more, about 500 times higher or more, or about 1000 times higher or more etc. than for the pathogenic microorganisms on the skin.

[0118] In another aspect, present invention relates to reducing or preventing one or more microorganisms from becoming invasive. These microorganisms may be part of the commensal or mutual flora of microorganisms.

[0119] In one non-limiting aspect, the commensal or mutual microorganisms may e.g. Staphylococcus epidermidis, Cutibacterium acnes, Corynebacterium species.

[0120] In a further aspect, the commensal or mutual microorganisms found on healthy adult skin may be with respect to bacteria;

[0121] - Sebaceous / oily sites: Cutibacterium (Propionibacterium) acnes', Staphylococcus epidermidis.

[0122] - Moist / flexural sites: Staphylococcus hominis., Corynebacterium spp. (e.g., C. ac- colens, C. striatum). - Dry sites (forearm, shin): Micrococcus luteus', Acinetobacter spp.; Streptococcus (mi- tis group).

[0123] And with respect to fungi (skin mycobiome)

[0124] - Dominant commensals: Malassezia yeasts — especially M. globosa, M. restricta, M. sympodialis.

[0125] In one non-limiting aspect, examples of potentially pathogenic microbes that may be present on healthy skin may be with respect to bacteria;

[0126] - Staphylococcus aureus — common human carrier state (especially nares, also skin / perineum) is a major risk factor for later infection.

[0127] - Staphylococcus lugdunensis — a coagulase-negative staphylococcus that resides on normal skin but can cause invasive infections akin to S. aureus.

[0128] - Pseudomonas aeruginosa — frequently a transient colonizer of moist skin sites (axilla, perineum, ear) in healthy people; can become pathogenic in wounds or macerated skin, or with respect to fungi;

[0129] - Candida spp. (e.g., C. albicans) — low-level colonization of intertriginous areas can be present on healthy skin and predispose to candidal intertrigo under favorable conditions.

[0130] An important aspect of present invention is that the composition according to present invention affects the commensal or mutual microorganisms to a lesser degree than pathogenic microbes and consequently displays a selectivity between the two groups of microorganisms.

[0131] Present invention also relates to the following items / embodiments:

[0132] 1. A composition comprising

[0133] - an oil phase from about 10%w / w to about 25%w / w of the total composition, wherein the oil phase comprises i) at least one oil each having a content of at least 80%w / w saturated fatty acids and wherein the total of said at least one oil makes up at least 35%w / w of the oil phase, and ii) at least one emulsifying agent, and

[0134] - an aqueous phase from about 75%w / w to about 90%w / w of the total composition, wherein the aqueous phase comprises at least one alkylene glycol selected from propylene glycol, butylene glycol, pentylene glycol, hexylene glycol or mixtures thereof, and wherein said at least one alkylene glycol makes up at least about 29%w / w of the aqueous phase. 2. The composition according to embodiment 1, wherein the weight ratio between the at least one alkylene glycol and water is from about 1:1 to about 1:3.

[0135] 3. The composition according to any of the preceding embodiments, wherein the weight ratio between the at least one alkylene glycol and water is from about 1:1.4 to about 1 :2.8.

[0136] 3.1. The composition according to any of the preceding embodiments, wherein the weight ratio between the at least one alkylene glycol and water is from about 1:1.7 to about 1 :2.5.

[0137] 3.2. The composition according to any of the preceding embodiments, wherein the weight ratio between the at least one alkylene glycol and water is from about 1:2.0 to about 1 :2.3.

[0138] 4. The composition according to any of the preceding embodiments, wherein said at least one alkylene glycol is propylene glycol.

[0139] 5. The composition according to any of the preceding embodiments, wherein said at least one oil is selected from the group consisting of vegetable oils, mineral oils, ester oils, silicon oils, and mixtures thereof.

[0140] 6. The composition according to any of the preceding embodiments wherein said at least one oil is a vegetable oil, such as coconut oil, olive oil, sunflower oil, cottonseed oil, palm oil and / or canola oil.

[0141] 7. The composition according to any of the preceding embodiments, wherein said at least one oil is coconut oil.

[0142] 8. The composition according to any of the preceding embodiments, wherein the weight ratio between the at least one alkylene glycol and the at least one oil contained in the composition is from 1:1 to about 5:1. 9. The composition according to any of the preceding embodiments, wherein the weight ratio between the at least one alkylene glycol and the at least one oil contained in the composition is from about 1.5:1 to about 4.8:1.

[0143] 9.1. The composition according to any of the preceding embodiments, wherein the weight ratio between the at least one alkylene glycol and the at least one oil contained in the composition is from about 1.8: 1 to about 4.5:1.

[0144] 9.2. The composition according to any of the preceding embodiments, wherein the weight ratio between the at least one alkylene glycol and the at least one oil contained in the composition is from about 2.0:1 to about 4.2:1.

[0145] 10. The composition according to any of the preceding embodiments, wherein the concentration of propylene glycol is from about 21%w / w to about 40%w / w such as from about 21%w / w to about 30%w / w, or from about 23%w / w to about 27%w / w.

[0146] 11. The composition according to any of the preceding embodiments, wherein the at least one alkylene glycol is propylene glycol, the concentration of propylene glycol in the composition is about 25%w / w, the at least one oil is coconut oil and the concentration of coconut oil in the composition is about 5 - 15%w / w such as from about 6 - 12%w / w.

[0147] 12. The composition according to any of the preceding embodiments wherein at least two of the emulsifying agents have a HLB (hydrophilic-lipophilic balance) in the range from about 3 to about 20.

[0148] 13. The composition according to any of the preceding embodiments comprising one or more emulsifying agents with a HLB from about 11 to about 20.

[0149] 14. The composition according to any of the preceding comprising one or more emulsifying agents with a HLB from about 3 to about 11.

[0150] 15. The composition according to any one of embodiments 12-14, wherein the emulsifying agents are each selected from the group consisting of glycerol alkyl esters, mac- rogol alkyl esters, polyoxyethyleneglycol alkyl esters, fatty acids, polyoxyethylene sorbi- tan esters, polyoxyethylene alkyl ethers and galactolipids. 16. The composition according to any one of the preceding embodiments, wherein the concentration of each of the emulsifiers in the composition is from about 0.3%w / w to about 5%w / w.

[0151] 17. The composition according to any one of embodiments 12-16, wherein the one or more emulsifying agents consist of glycerol monostearate 40-55, macrogol stearate and stearic acid.

[0152] 18. The composition according to embodiment 17, wherein the concentration ratio in the composition between glycerol monostearate 40-55, macrogol stearate and stearic acid is about 6:6:1 - 6:6:4, such as the concentrations in the composition being about 3%w / w, about 3%w / w and (0.5%w / w - 2%w / w) of the total composition, respectively.

[0153] 19. The composition according to any of the preceding embodiments containing a viscosity-increasing agent, such as a fatty alcohol and / or a biodegradable polymer.

[0154] 19.1. The composition according to embodiment 19, wherein the viscosity-increasing agent is cetostearyl alcohol.

[0155] 19.2 The composition according to embodiment 19, wherein the viscosity-increasing agent is hypromellose.

[0156] 20. The composition according to any of the preceding embodiments, which comprises a humectant.

[0157] 21. The composition according to embodiment 20, wherein said humectant is glycerol.

[0158] 22. The composition according to any of embodiments 20-21, wherein the concentration of said humectant in the composition is from about 0.1%w / w to about 10%w / w.

[0159] 23. The composition according to any of embodiments 20-22, wherein the concentration of said humectant in the composition is from about 3%w / w to about 7%w / w.

[0160] 24. The composition according to any of embodiments 20-23, wherein the concentration of said humectant in the composition is 4% w / w. 25. The composition according to any of the preceding embodiments, which do not contain an active drug substance.

[0161] 26. The composition according to any of the preceding embodiments containing: 21-40 % w / w of propylene glycol,

[0162] 5-15% w / w of a vegetable oil,

[0163] 1-10% w / w of one or more emulsifying agents, optionally 0.1-1 % w / w of a pH adjusting agent, optionally 0.2-7% w / w viscosity increasing agents, up to 100% w / w of water.

[0164] 27. The composition according to any of the preceding embodiments containing: 21-40% w / w of propylene glycol,

[0165] 6-12% w / w of a vegetable oil,

[0166] 4-8% w / w of one or more emulsifying agents,

[0167] 0.1-1 % w / w of a pH adjusting agent to adjust pH of the composition to about 4-6, 0.2-7% w / w viscosity increasing agents, up to 100% w / w of water.

[0168] 28. The composition according to any of the preceding embodiments containing: from 21 to 30 % w / w of propylene glycol, from 6%w / w to 12% w / w of a vegetable oil, from 4%w / w to 8% w / w of one or more emulsifying agents,

[0169] 0.1-1 % w / w of a pH adjusting agent to adjust pH of the composition to about 4-6, 0.2-7% w / w viscosity increasing agents, up to 100% w / w of water.

[0170] 29. The composition according to any of the preceding embodiments with the proviso that the composition does not contain any preservatives apart from the preservative effect from any of the specified components.

[0171] 30. The composition according to any of the preceding embodiments which contains:

[0172] 31. The composition according to any of the previous embodiments, which is a cosmetic composition. 32. The composition according to any of the preceding embodiments, which is a cutaneous emulsion composition.

[0173] 33. The composition according to any of the preceding embodiments, which is an o / w emulsion composition.

[0174] 34. The composition according to any of the preceding embodiments for use where the normal skin barrier function remains unaffected.

[0175] 35. The composition according to any of the preceding embodiments for use as an anti- microbial composition.

[0176] 36. The composition according to any of the preceding embodiments for use as an antimicrobial cutaneous emulsion for application onto an infected skin area. 37. The composition according to any of the preceding embodiments for use in a method for the treatment of infected skin.

[0177] 38. The use according to embodiment 37, wherein said composition is applied to the infected skin area once daily for a period of at least 14 days, at least 30 days or at least 60 days.

[0178] 39. The use according to embodiment 37, wherein said composition is applied to the infected skin area twice or thrice daily for a period of at least 14 days, at least 30 days or at least 60 days.

[0179] 40. The composition according to any of the preceding embodiments for use as an antipruritic composition.

[0180] 41. The composition according to any of the preceding embodiments for use in a method for the treatment of pruritus.

[0181] 42. The use of a composition according to any of the preceding embodiments for the application to a dry skin area to obtain a long softening and moisturizing effect.

[0182] 43. The use of a composition according to any of the preceding embodiments for the application to a skin area to obtain a long softening, moisturizing effect while preserving the normal skin barrier function.

[0183] 44. The composition according to any of the preceding embodiments, which has a stability of at least 24 months when stored at 25 °C in a suitable primary packaging, wherein the stability is assessed by quantifying the physical stability, viscosity and pH, and product microbial quality.

[0184] 45. A process for preparing the composition as defined in any of embodiments 1-44, comprising the steps: i) preparing the oil phase by mixing the ingredients that make up the oil phase and heating to a temperature of from 60 °C to 80 °C, notably from 65 °C to 75 °C such as about 70 °C, ii) preparing the aqueous phase by dissolving the ingredients that make up the aqueous phase, optionally by heating to 55 °C to 75 °C, notably from 60 °C to 70 °C such as about 65 °C, iii) mixing the oil phase i) and the aqueous phase ii) until an emulsion is obtained, iv) optionally, subjecting the thus obtained emulsion to vacuum conditions, v) optionally, homogenizing the emulsion optionally under vacuum conditions, vi) optionally, addition of one or more fragrance agents, vii) cooling the thus obtained emulsion.

[0185] 46. The process according to embodiment 45, which comprises the step iv).

[0186] 47. The process according to any of embodiments 45-46, which comprises the step v).

[0187] 48. The process according to any of embodiments 45-47, which comprises the step vi).

[0188] 49. The process according to embodiment 45, which consists of the steps i), ii), iii), iv), v) and vii).

[0189] The invention is further illustrated in the Figures and Examples without limiting the invention thereto.

[0190] Examples

[0191] Examples of the composition according to the invention are given herein.

[0192] Table 1. Example 1-4, composition of 300 g cutaneous emulsion batches. TOTAL | 1000 | 1000 | 1000 | 1000 |

[0193] Table 2. Example 5-8, composition of 300 g cutaneous emulsion batches.

[0194] Table 3. Example 9-11 , composition of 3 kg cutaneous emulsion batches.

[0195] Table 4. Examples 12-14 are compositions of 3 kg cutaneous emulsion batches and example 15 is a composition of a 20 kg cutaneous emulsion batch.

[0196]

[0197] Table 5. Example 16-18, composition of 3 kg cutaneous emulsion batches.

[0198] Table 6. Example 19-22, composition of 20 kg cutaneous emulsion batches. More specifically, the invention relates to a composition according to Table 7.

[0199] Table 7. Complete composition of the invention

[0200] Example 23

[0201] The complete composition according to Example 20 of the present invention, together with examples of replacement ingredients, is given in Table 8. Table 8. Complete composition of 25% propylene glycol oil-in-water cutaneous emulsion according to the invention. Example 24.

[0202] Description of manufacturing process.

[0203] A process for preparing the composition of Example 20.

[0204] Propylene glycol and water are mixed and heated to about 65°C together with sodium citrate and citric acid.

[0205] The ingredients of the oil phase (coconut oil, cetostearyl alcohol, macrogol stearate, glycerol monostearate 40-55 and stearic acid) are mixed and heated to about 70°C.

[0206] The oil phase is added to the aqueous phase. The composition is mixed and homogenized and thereafter the cream is cooled during stirring.

[0207] One detailed process for preparing a composition of the invention is:

[0208] 1. Mixing and heating of water phase to clear solution.

[0209] Add pH adjusting agents, alkylene glycol and purified water to a vessel. Heat to 65°C + 5°C during mixing at low speed. Control that a clear solution is obtained.

[0210] 1. Add raw material to the oil phase.

[0211] Add all the raw materials of the oil phase to a vessel.

[0212] 3. Melting and heating of oil phase

[0213] Heat and melt the oil phase to 70°C + 5°C.

[0214] 4. Mixing the oil phase to a homogeneous solution.

[0215] Control that the oil phase is a homogeneous solution.

[0216] 5. Transfer the oil phase to the water phase.

[0217] Transfer all the oil phase to the water phase.

[0218] 6. Mixing.

[0219] Mix the two phases until a white emulsion has emerged. Use medium mixing speed. 7. Add vacuum.

[0220] Carefully add vacuum.

[0221] 8. Homogenisation.

[0222] Homogenize the emulsion for about 5 - 10 minutes, while stirring.

[0223] 9. Cooling.

[0224] Cool the emulsion while stirring, until the temperature of the emulsion reaches about 25°C.

[0225] 10. Final mixing.

[0226] When the emulsion has reached a temperature of 25°C, mix for additional 15 minutes at low speed.

[0227] Example 25.

[0228] Composition according to Example 21 , that don’t alter the normal skin barrier resistance, i.e. skin barrier function.

[0229] Skin membranes from porcine ears were produced with a dermatome (TCM 3000 BL; Nouvag, Goldach, Switzerland) to a thickness of approximately 500 pm. Before initiating the experiment, the skin was allowed to hydrate for one hour at 32°C in the diffusion cells with the dermal side exposed to the receptor media and with the stratum corneum side exposed to the ambient air. The compositions were applied as infinite doses (260 mg / cm2). The diffusion cells were occluded with Parafilm to maintain fixed boundary conditions.

[0230] The membrane impedance spectroscopy set-up comprised Franz cell (orifice diameter = 9 mm, Vreceptor = 6mL; Permegear Inc., Hellerstown, USA) with four electrodes connected to a potentiostat from Ivium Technologies (Eindhoven, the Netherlands). The electrodes were connected as working electrode (Pt) and sensing electrode (Ag / AgCI) in the donor chamber and as counter electrode (Pt) and reference electrode (Ag / AgCI) in the receptor chamber of the Franz cell. For impedance measurements, an alternating voltage of 20mV amplitude was applied. The system was controlled with Ivium software, which performed a frequency sweep between 1 Hz and 6MHz with frequency steps of 5 points per decade (35 points in total per scan). Data from the impedance measurements, Z, of the porcine skin membranes were modelled as an equivalent circuit consisting of a constant phase element in parallel with the resistance, R, of skin. The capacitance, C was calculated by exploiting the power-law formula proposed by Hirschorn et al. (2010) J Electrochem Soc 157(12): C452-C457.

[0231] The structural features of the lipid layers in the stratum corneum are reflected by the effective dielectric constant, £ (White et al. (2013) Pharm Res 30(10): 2607-2624. A higher £ value indicates that the extracellular lamellar lipid matrix in the stratum corneum has an increased fraction of lipids in the fluid state, and in many studies it has been shown that molecular diffusion in lipids is facilitated by a transition from the crystalline to the liquid crystalline state (Hadgraft (2004) European Journal of Pharmaceutics and Biopharmaceutics 58: 291-299, and Welin-Berger et al. (2002) J. Controlled Release 81 (1-2): 33-43). An increase in the fluidity of the stratum corneum extra cellular lipids results in an increase in the penetration of e.g. environmental chemicals, allergens and microorganisms potentially triggering skin inflammation and infections.

[0232] The dielectric constant, E is related to the capacitance according to: £ = ((C / A) x L) / £o

[0233] Where, C is the capacitance, A is the area of the skin membrane, L is the thickness of the main barrier, stratum corneum and £o is the permittivity of vacuum (8.8542 x 10-12 F / m).

[0234] When comparing the dielectric properties of the porcine skin, measured before and after application of the composition according to Example 21 according to the invention and one commercial petrolatum jelly (Vaseline) based cream composition the resulting ratio £after / £before showed a mean value of 0.71 for the invention and 1 .94 for the commercial cream.

[0235] This data shows that the composition according to the invention do not increase the lipid fluidity and hence do not increase the possible skin permeability for environmental allergens or microorganisms. The commercial cream increased the stratum corneum lipid fluidity by a factor of approximately 2, making the skin more susceptible for environmental allergen and microorganism permeation.

[0236] Furthermore, a substantial decrease in skin resistance was seen on application of the commercial cream (mean Rafter / Rbefore = 0.16), which also indicated that the lipid matrix in skin became more fragmented and disturbed. For the composition according to the invention, no significant difference in resistance before and after application could be detected (mean Rafter / Rbefore = 1.14). Example 26.

[0237] Composition according to Example 21 and Example 22 with anti-microbial effect.

[0238] The antimicrobial effect of the invention has been investigated according to Ph. Eur. 5.1.3. Tests for efficacy of antimicrobial preservation, for cutaneous use.

[0239] The results of the tests on Example 21 , for both bacteria and fungi satisfied Criteria A, with 2 log reductions after 48 hours, 3 log reductions after 7 days, no increase after 28 days for bacteria; and 2 log reductions after 14 days and no increase after 28 days for fungi. The potential pathogenic bacteria included in the tests were the gram-positive S. aureus and the gram-negative P. aeruginosa, and the fungi were the opportunistic pathogen C. albicans and A. niger.

[0240] The same tests were performed for Example 22. The corresponding results for this formulation satisfied Criteria A for the bacteria S. aureus and P. aeruginosa, and Criteria A for the fungi C. albicans, whereas only Criteria B was satisfied for the fungi A. niger with 1 log reduction after 14 days and no increase after 28 days.

[0241] Figures 1-4 demonstrates the antimicrobial effect of the invention on skin relevant microbes, the potential pathogenic gram-positive bacteria S. aureus and gram-negative P. aeruginosa together with the opportunistic pathogenic fungi C. albicans and A. niger.

[0242] The concentration, 25% propylene glycol, is optimal since higher concentrations gives a less cosmetic preferred composition. In addition, the concentration of propylene glycol should be kept as low as possible since higher concentrations also could pose a medical problem such as e.g. hyperosmolarity, especially when used on children with large areas of disrupted skin barrier. This concentration makes the invention self-preserved thereby excluding the need of preservatives. Different preservatives are often in question when it comes to safety. In addition, it is questionable what microbes, pathogenic or commensals that will be affected on the skin when specific preservatives are used. Commonly used preservatives are e.g. the parabens.

[0243] Propylene glycol unlike many specific preservatives, anti-microbial agents and antibiotics shows a broad antimicrobial spectrum. This is important when considering the microbiota and possible negative effects on suppressing specific microbes that gives other less sensitive, potential pathogenic microbes increased growth possibilities. Example 27.

[0244] Investigating the selective antimicrobial effect of propylene glycol on bacterial species with different pathogenicity.

[0245] Propylene glycol unlike many specific preservatives, anti-microbial agents and antibiotics shows a broad antimicrobial spectrum (Bhat KS, Walwekar SV. Evaluation of bactericidal property of propylene glycol for its possible use in endodontics. Arogya J Health Sci 1975; 1 :54-9). This is important when considering the skin microbiota. Potential pathogens like S. aureus, known to cause activation of pruriceptor sensory neurons to drive itch causing robust itch and scratch-induced skin damage, is probably the most important microbe to control and reduce when considering dry and infected skin. The commensal microbes, e.g. S. epidermidis should ideally not be reduced to the same extent thereby conserving the skin microbiota and hampering recolonization of S. aureus.

[0246] S. aureus ZB and S. epidermidis ZA strains were isolated from the skin of a healthy person and grown on Brain Heart Infusion (BHI) broth in 5% carbon dioxide (CO2) at 37°C for 24 h. For each strain, 5 single colonies were transferred to a liquid medium of BHI broth with pH either 5.0 or 7.4 and incubated overnight (17-18 h) at 37°C and 5% CO2. A volume of 1 mL of the overnight bacterial cells suspension was pelleted at 3000 rpm for 10 min and resuspended in Mueller-Hinton (MH) broth. Subsequently, the individual bacterial suspensions were diluted with MH broth (pH 5.0 or 7.4, respectively) by 25 times for S. aureus and by 10 times for S. epidermidis. The final concentration of each bacterium in the culture was about 105colony-forming units per millilitre (CFU mL"1).

[0247] Separate bacterial suspensions of S. aureus or S. epidermidis with the concentration of about 105CFU mL-1were used to inoculate the medium in sterile Greiner flat-bottomed plates 96 plate wells. Each well contained 100 pL of inoculum and 100 pL of MH broth of appropriate pH with propylene glycol in the final concentrations. Each negative control (blank) well contained 200 pL of MH broth. Each positive control well contained 100 pL of inoculum and 100 pL of MH broth. Each of the combinations was done in tripli- cate. After inoculation, microplates were covered with a sterile Breathe-Easy® gas permeable sealing membrane and incubated for 24-48 hours at 37°C in a SPECTRO-star Nano plate reader. Absorbance was recorded at 600 nm every 2 h with a 30s double orbital shaking (300rpm) prior to each absorbance reading.

[0248] At neutral pH (7.4) the inhibitory effect of 12.5% propylene glycol on the pathogen S. aureus is low whereas surprisingly high at the skin relevant pH (5.0) as shown in Figure 5 and 6. For the commensal S. epidermidis the inhibitory effect is low at neutral pH (7.4) and surprisingly also low at the skin relevant pH (5.0) as shown in Figure 7 and 8. The results thus surprisingly show that the pathogen and itch inducing microbe S. aureus is inhibited to a higher extent with a difference of approximately 100 times, by propylene glycol than the commensal microbe S. epidermidis at skin relevant pH (5.0) in the experimental setting used.

[0249] This is additionally shown visually when the two bacteria are grown together (1 :1) with (lower row) and without (upper row) 12.5% propylene glycol at pH 5.0 by studying the colony forming units plated on agar plates of the co-culture after 24 h and 48 h of incubation, according to Figure 9.

[0250] Example 28.

[0251] Investigation of humectant properties of propylene glycol.

[0252] Propylene glycol is a widely used humectant in topical products intended for dry skin. Other humectants commonly used in skin care products are e.g. salts such as sodium chloride together with glycerol and urea.

[0253] Skin moisture measurements were performed on two volunteers by conductance using DermaLab equipped with hydration probe from Cortex Technology. Baseline values was measured on the marked skin sites prior application of test formulations. The test formulations were applied to the volar aspect of the forearms, using occlusive Finn chambers (0 18 mm, 300 pl). After 3h the formulations were removed with a dry soft tissue followed by two rapid tape stripping to remove excess formulation from the skin surface. Immediately thereafter, the skin conductance was measured = time 0 h (untreated control), followed by measurements after 1.5 h, 2 h and 18 h. The different humectants were formulated in a hydrogel base formulation consisting of 2 % w / w hydroxypropylcellulose (HPC) in water. The humectants investigated, in commercial relevant concentrations, were: 1 Untreated control (blank)

[0254] 2 Base formulation

[0255] 3 Base formulation + 4% sodium chloride

[0256] 4 Base formulation + 5% urea

[0257] 5 Base formulation + 25% propylene glycol

[0258] According to Figure 10, the skin moisturizing effect of the base formulation (BF) with 4 % sodium chloride was only slightly better than the BF alone. BF with 5 % urea showed an improvement in moisturizing effect compared to the BF alone and BF with 4% NaCI. BF with 25 % propylene glycol showed an improved moisturizing effects as compared to all other test formulations.

[0259] In the concentration used, propylene glycol showed superior skin hydration effect for up to 2 h, measured as skin conductance, as compared to sodium chloride and urea.

[0260] Example 29

[0261] As illustrated in the above examples, the composition according to the invention displays a selectivity between pathogenic microorganisms and commensal microorganisms in the sense that the latter is affected to a lower degree. A composition according to Table 7 and also examples 21 and 22 showed a similar trend and on selectivity between S. aureus and S. epidermis as seen in Fig. 6 and Fig. 8 respectively and consequently showcasing the selectivity of the composition in terms of affecting the two bacterial species differently. This was compared to other substances used in the art in topical compositions.

[0262] A study was undertaken to determine whether cetylpyridinium chloride (a cationic quaternary ammonium surfactant with antimicrobial properties, CPC) glove coatings are effective against the common skin-inhabiting bacteria Staphylococcus epidermidis and Staphylococcus aureus. The in vitro MIC of CPC against each of the test organisms was determined as 0.3 pg / ml. Consequently, this agent did not show any selectivity between the two Staphylococcus species.

[0263] In another study, the effect of C31G (equimolar mixture of N-alkyl betaine and N-alkyl- N,N dimethylamine oxide) was investigated. The minimum inhibitory concentration was determined for C31G according to the broth microdilution method: Two-fold serial dilutions of the antimicrobial in cation-adjusted Mueller-Hinton broth (CAMHB) across the range 0.06 - 64 pg / mL was prepared. Inoculum of ~5 x 105CFU / mL in each well (prepared from a fresh 0.5 McFarland suspension and diluted appropriately). Equal volumes of drug solution and inoculum were dispensed, 100 pL + 100 pL into sterile 96- well microplates. Growth control and solvent control was included. Samples were incubated at 35 ± 2 °C, ambient air, for 20 h. The MIC was determined as the lowest concentration with no visible growth (no turbidity or pellet).

[0264] The measured MIC values were equal, 4 pg / mL for both test bacteria, S. aureus ZB and S. epidermidis Z / X. No selectivity was detected for the equimolar mixture of N-alkyl betaine and N-alkyl-N,N dimethylamine oxide (C31G).

Claims

1. 42Claims1. A cutaneous o / w emulsion composition for use as a topical moisturizing, anti-itch, anti-infectious and anti-microbial composition for administration on the skin, comprising an oil phase from about 10%w / w to about 25%w / w of the total composition, wherein the oil phase comprises i) at least one oil each having a content of at least 80%w / w saturated fatty acids and wherein the total of said at least one oil makes up at least 35%w / w of the oil phase, and ii) at least one emulsifying agent, and an aqueous phase from about 75%w / w to about 90%w / w of the total composition, wherein the aqueous phase comprises at least one alkylene glycol selected from propylene glycol, butylene glycol, pentylene glycol, hexylene glycol or mixtures thereof, and wherein said at least one alkylene glycol makes up at least about 29%w / w of the aqueous phase, whereby pathogenic microorganisms are reduced to a higher extent as compared to the commensal microbiota or microorganisms.

2. The composition for use according to claim 1 , wherein the weight ratio between the at least one alkylene glycol and water is from about 1 :1 to about 1 :3.

3. The composition for use according to any one of the preceding claims, wherein said at least one alkylene glycol is propylene glycol.

4. The composition for use according to any of the preceding claims, wherein said at least one oil is selected from the group consisting of vegetable oils, mineral oils, ester oils, silicon oils, and mixtures thereof.

5. The composition for use according to any of the preceding claims, wherein said at least one oil is coconut oil.

6. The composition for use according to any of the preceding claims, wherein the weight ratio between the at least one alkylene glycol and the at least one oil contained in the composition is from 1:1 to about 5:1.

7. The composition for use according to any of the preceding claims, wherein the at least one alkylene glycol is propylene glycol and wherein the concentration of propylene glycol in the composition is from about 21%w / w to about 40%w / w such as from about 21 %w / w to about 30%w / w, or from about 23%w / w to about 27%w / w.

438. The composition for use according to any of the preceding claims wherein the emulsifying agents have a HLB (hydrophilic-lipophilic balance) in the range from about 3 to about 20.

9. The composition for use according to any of the preceding claims, wherein the emulsifying agents are each selected from the group consisting of glycerol alkyl esters, macrogol alkyl esters, polyoxyethyleneglycol alkyl esters, fatty acids, polyoxyethylene sorbitan esters, polyoxyethylene alkyl ethers and galactolipids.

10. The composition for use according to any one of the preceding claims, wherein the concentration of each of the emulsifiers in the composition is from about 0.3%w / w to about 5%w / w.11 . The composition for use according to any of the preceding claims containing a viscosity-increasing agent, such as a fatty alcohol and / or a biodegradable polymer, more specifically cetostearyl alcohol and / or hypromellose.

12. The composition for use according to any of the preceding claims, wherein the one or more viscosity-increasing agents ranges from about 0.2%w / w to about 7%w / w based on the total composition.

13. The composition for use according to any of the preceding claims, which comprises a humectant, wherein said humectant is selected from simple triols, i.e. glycerol, wherein the concentration of glycerol in the composition is up to about 4%w / w.

14. The composition for use according to any of the preceding claims, adjusted to a pH below 6, such as e.g. from about 4.5 to about 5.5, or about 5.0.

15. The composition for use according to any of the preceding claims, which has no content of an active drug substance.

16. The composition for use according to any of the preceding claims, wherein the pathogenic microorganisms are reduced by about 1 .5 times more than the commensal or mutual microorganisms on the skin (counted as CFU / ml), or about 2 times more, or44 about 2,5 times more, or about 3 times more, or about 4 times more, or about 5 times more, or about 6 times more, or about 7 times more, or about 8 times more, or about 9 times more, or about 10 more, or about 20 times more, about 50 times more, about 75 times more, about 100 times or more etc. than the commensal or mutual microorganisms on the skin.

17. The composition for use according to claim 16, wherein the reduction is observed or measured after 24h after topical application, or after 48h after topical application.

18. The composition for use according to any of the preceding claims, wherein the composition comprises:21-40 %w / w of propylene glycol,6-12%w / w of a vegetable oil,1-10%w / w of one or more emulsifying agents,0,2-7%w / w of one or more viscosity increasing agents selected from the fatty alcohols and / or biodegradable polymers, optionally up to about 4%w / w of a humectant selected from the simple triols, optionally up to about 2%w / w of a non-cyclic silicone oil, optionally 0.1-1%w / w of one or more pH adjusting agents, up to 100%w / w of water.

19. The composition for use according to any of the preceding claims, wherein the composition consists of or comprises the components and amounts according to the below;

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