Non-therapeutic and therapeutic use of hydroxycinnamic acid & derivatives

Abstract

The present invention generally relates to the use of hydroxycinnamic acid or derivatives thereof, such as zosteric acid in a cosmetic or therapeutic setting. The present invention further relates to compositions comprising hydroxycinnamic acid or derivatives thereof.

Description

Non-therapeutic use of hydroxycinnamic acid & derivativesTechnical Field

[0001] The present invention relates to the use of hydroxycinnamic acid or derivatives thereof, such as zosteric acid in a cosmetic or therapeutic setting. The present invention further relates to compositions comprising hydroxycinnamic acid or derivatives thereof.Background

[0002] The human or animal skin and scalp, serving as primary barriers against external environmental factors, are prone to a variety of conditions, both cosmetic and therapeutic in nature. These conditions can profoundly impact the physical well-being of individuals and often bear psychological and emotional burdens due to their conspicuous nature.

[0003] Cosmetically, challenges such as acne, wrinkles, rosacea, and the likes have long troubled many individuals, leading to a continuous quest for effective solutions to prevent or mitigate these topical conditions. Acne, for instance, manifesting as pimples, blackheads, and cysts, affects a significant portion of the population, often due to a combination of factors including microbial activity. Likewise, conditions like wrinkles, commonly seen as an inevitable sign of aging, are exacerbated by external factors like UV radiation, pollution, and certain lifestyle choices.

[0004] On the scalp, conditions such as dandruff, dryness, oiliness, and scalp acne can significantly impact an individual's confidence and overall comfort. Dandruff, characterized by the flaking of the scalp, can often be attributed to a combination of factors, including the presence of specific microorganisms.

[0005] Beyond cosmetic concerns, numerous skin conditions have therapeutic implications. Disorders such as seborrheic dermatitis, tinea versicolor, scalp folliculitis, and alopecia areata can not only cause significant discomfort but may also lead to complications in severe cases. Notably, many of these conditions have a direct or indirect link to microbial infections.

[0006] Current treatments and preventive methodologies, although extensive, often present challenges like side effects, resistance, limited efficacy, or targeting only specific symptoms rather than the root causes. There's a pronounced and unaddressed need for compositions and solutions that can address either or both cosmetic and therapeutic skin and scalp issues.Summary

[0007] The present inventors have surprisingly discovered that a class of compounds, namelyhydroxycinnamic acid or derivatives thereof, in particular sulfated variants, such as Zosteric acid are capable of decreasing antimicrobial adherence enabling prevention or alleviation of cosmetic conditions. In some aspects, the hydroxycinnamic acid or derivatives thereof are also suitable for use in therapy.

[0008] Thus, in one aspect the present disclosure provides cosmetic use of a composition comprising a hydroxycinnamic acid or a derivative thereof for preventing and / or alleviating a topical condition on a subject.

[0009] In one aspect, the present disclosure provides a composition comprising a hydroxycinnamic acid or derivative thereof according to the formula:, or a salt thereof, wherein Ri, R2 and R3 independently are selected from the group consisting of hydrogen (H), hydroxyl (OH), Ci-6-alkyl and Ci-g-alkoxy, -O-SO2-OR5, wherein R5is selected from the group consisting of: hydrogen and Ci.g-alkyl; provided that at least one of Ri, R2 and R3 is hydroxyl (OH) or -O-SO2-OR5, and R4is selected from the group consisting of hydrogen (H) and Ci-g-alkyl.

[0010] In one aspect, the present disclosure provides a cosmetic product comprising the composition as defined herein.

[0011] In one aspect, the present disclosure provides a composition comprising hydroxycinnamic acid or a derivative thereof for use in the treatment of a skin disorder.Description of drawings and figures

[0012] The figures included herein are illustrative and simplified for clarity, and they merely show details which are essential to the understanding of the invention, while other details may have been left out. Throughout the specification, claims and drawings the same reference numerals are used for identical or corresponding parts. In the figures and drawing include herein:Figure 1 shows microbial growth in liquid and solid media. M. furfur was grown in liquid media in the presence of Zosteric acid at the indicated concentrations (left), and the minimum inhibitory concentration (MIC) was determined as the lowest concentration of product thatcompletely inhibited growth (measured by OD600). On the right, the liquid cultures from the MIC experiment were plated to check for microbial growth in solid media, and the minimum microcidal concentration (MMC) was determined as the lowest concentration of product that inhibited growth (determined by lack of visible colonies). Data are represented as Mean ± Std and the statistical significance was calculated compared to the non-treated control and depicted as follows; **** p value < 0.0001.Figure 2 shows microbial growth in liquid and solid media. M. restricta was grown in liquid media in the presence of Zosteric acid at the indicated concentrations (left), and the minimum inhibitory concentration (MIC) was determined as the lowest concentration of product that completely inhibited growth (measured by OD600). On the right, the liquid cultures from the MIC experiment were plated to check for microbial growth in solid media, and the minimum microcidal concentration (MMC) was determined as the lowest concentration of product that inhibited growth (determined by lack of visible colonies). Data are represented as Mean ± Std and the statistical significance was calculated compared to the non-treated control and depicted as follows; **** p value < 0.0001.Figure 3 shows microbial growth in liquid and solid media. S. aureus CECT239 was grown in liquid media in the presence of Zosteric acid at the indicated concentrations (left), and the minimum inhibitory concentration (MIC) was determined as the lowest concentration of product that completely inhibited growth (measured by OD600). On the right, the liquid cultures from the MIC experiment were plated to check for microbial growth in solid media, and the minimum microcidal concentration (MMC) was determined as the lowest concentration of product that inhibited growth (determined by lack of visible colonies). Data are represented as Mean ± Std and the statistical significance was calculated compared to the non-treated control and depicted as follows; **** p value < 0.0001.Figure 4 shows microbial growth in liquid and solid media. S. aureus V329 was grown in liquid media in the presence of Zosteric acid at the indicated concentrations (left), and the minimum inhibitory concentration (MIC) was determined as the lowest concentration of product that completely inhibited growth (measured by OD600). On the right, the liquid cultures from the MIC experiment were plated to check for microbial growth in solid media, and the minimum microcidal concentration (MMC) was determined as the lowest concentration of product that inhibited growth (determined by lack of visible colonies). Data are represented as Mean ± Std and the statistical significance was calculated compared to the non-treated control and depicted as follows; **** p value < 0.0001.Figure 5 shows microbial growth in liquid and solid media. S. epidermidis was grown in liquidmedia in the presence of Zosteric acid at the indicated concentrations (left), and the minimum inhibitory concentration (MIC) was determined as the lowest concentration of product that completely inhibited growth (measured by OD600). On the right, the liquid cultures from the MIC experiment were plated to check for microbial growth in solid media, and the minimum microcidal concentration (MMC) was determined as the lowest concentration of product that inhibited growth (determined by lack of visible colonies). Data are represented as Mean ± Std and the statistical significance was calculated compared to the non-treated control and depicted as follows; **** p value < 0.0001.Figure 6 shows microbial growth in liquid and solid media. C. acnes was grown in liquid media in the presence of Zosteric acid, and the minimum inhibitory concentration (MIC) was determined as the lowest concentration of product that completely inhibited growth (measured by OD600). The liquid cultures from the MIC experiment were plated to check for microbial growth in solid media, and the minimum microcidal concentration (MMC) was determined as the lowest concentration of product that inhibited growth (determined by lack of visible colonies). Data are represented as Mean ± Std and the statistical significance was calculated compared to the non-treated control and depicted as follows; **** p value < 0.0001.Figure 7 shows a graphical representation of the results showing raw (ufc / ml, left) and normalized (right) number of adherent cells to the pig skin explant treated with Zosteric acid at the indicated concentrations after 1 h, including an inoculated, non-treated control. Data are presented as mean ± standard error of the median (SEM). Statistical significance is depicted as * for p < 0.05, *** for p < 0.001.Figure 8 shows a graphical representation of the results showing raw (ufc / ml, left) and normalized (right) number of adherent cells to the pig skin explant treated with Zosteric acid at the indicated concentrations after 24 h, including an inoculated, non-treated control. Data are presented as mean ± standard error of the median (SEM).Figure 9 shows a graphical representation of the results showing raw (ufc / ml, left) and normalized (right) number of adherent cells to the pig skin explant treated with Zosteric acid at the indicated concentrations after 1 h, including an inoculated, non-treated control. Data are presented as mean ± standard error of the median (SEM). Statistical significance is depicted as * for p < 0.05, ** for p < 0.01, **** for p < 0.0001.Figure 10 shows a graphical representation of the results showing raw (ufc / ml, left) and normalized (right) number of adherent cells to the pig skin explant treated with Zosteric acid at the indicated concentrations after 24 h, including an inoculated, non-treated control. Dataare presented as mean ± standard error of the median (SEM). Statistical significance is depicted as * for p < 0.05, ** for p < 0.01, *** for p < 0.001.Figure 11 shows a graphical representation of the results showing raw (ufc / ml, left) and normalized (right) number of adherent cells to the pig skin explant treated with Zosteric acid at the indicated concentrations after 1 h, including an inoculated, non-treated control. Data are presented as mean ± standard error of the median (SEM). Statistical significance is depicted as * for p < 0.05.Figure 12 shows a graphical representation of the results showing raw (ufc / ml, left) and normalized (right) number of adherent cells to the pig skin explant treated with Zosteric acid at the indicated concentrations after 24 h, including an inoculated, non-treated control. Data are presented as mean ± standard error of the median (SEM). Statistical significance is depicted as * for p < 0.05, ** for p < 0.01.Figure 13 shows a graphical representation of the results showing raw (ufc / ml, left) and normalized (right) number of adherent cells to the pig skin explant treated with Zosteric acid at the indicated concentrations after 1 h, including an inoculated, non-treated control. Data are presented as mean ± standard error of the median (SEM). Statistical significance is depicted as **** for p < 0.0001.Figure 14 shows a graphical representation of the results showing raw (ufc / ml, left) and normalized (right) number of adherent cells to the pig skin explant treated with Zosteric acid at the indicated concentrations after 24 h, including an inoculated, non-treated control. Data are presented as mean ± standard error of the median (SEM). Statistical significance is depicted as * for p < 0.05, ** for p < 0.01.Figure 15 shows a graphical representation of the results showing raw (ufc / ml, left) and normalized (right) number of adherent cells to the pig skin explant treated with Zosteric acid at the indicated concentrations after 1 h, including an inoculated, non-treated control. Data are presented as mean ± standard error of the median (SEM). Statistical significance is depicted as * for p < 0.05, ** for p < 0.01.Figure 16 shows a graphical representation of the results showing raw (ufc / ml, left) and normalized (right) number of adherent cells to the pig skin explant treated with Zosteric acid at the indicated concentrations after 24 h, including an inoculated, non-treated control. Data are presented as mean ± standard error of the median (SEM). Statistical significance is depicted as * for p < 0.05, ** for p < 0.01, *** for p < 0.001.Figure 17 shows a graphical representation of the results showing raw (ufc / ml, left) and normalized (right) number of adherent cells to the pig skin explant treated with Zosteric acidat the indicated concentrations after 1 h, including an inoculated, non-treated control. Data are presented as mean ± standard error of the median (SEM). Statistical significance is depicted as * for p < 0.05, ** for p < 0.01.Figure 18 shows a graphical representation of the results showing raw (ufc / ml, left) and normalized (right) number of adherent cells to the pig skin explant treated with Zosteric acid at the indicated concentrations after 24 h, including an inoculated, non-treated control. Data are presented as mean ± standard error of the median (SEM). Statistical significance is depicted as ** for p < 0.01.Figure 19 shows a representative image of a sebum measurement conducted with Sebumeter® on the scalp.Figure 20 shows the dandruff scale. Scored between Grade 1 (Non dandruff) and Grade 5 (Severe).Figure 21 shows Graphical representation of sebum levels. The Mean and Standard Error of the Mean (SEM) are shown. Asterisks represents statistical significance with ****p-value <0,0001.Figure 22 shows Graphical representation of dandruff scale. The Mean and Standard Error of the Mean (SEM) are shown. Asterisks represents statistical significance with ****p-value <0,0001.Figure 23 shows a Bio Blue Light Scanner including a high-resolution camera (Dalsa TS, 5 Mpixels) and a diffuse and indirect lighting system, emitting at 470 nm (blue light).Figure 24 shows the scaliness scale employed for the study. Left to right increasing scaliness level (black to white). The bigger the number of corneocytes adhered to the Corneofix®, the bigger the scaliness level.Figure 25 shows the comedones (white head) scale used in Example 3.Figure 26 shows the graphical representation of area, volume, height and count of acne, respectively. The Mean and Standard Error of the Mean (SEM) are shown. Statistical significance is depicted as; * for p-value < 0,05.Figure 27 shows the graphical representation of skin scaliness. The Mean and Standard Error of the Mean (SEM) are shown.Figures 28 and 29 show the graphical representation of results of self-assessment questionnaires for or Examples 2 (Figure 29) and 3 (Figure 28).Figure 30 shows the microbial growth in liquid and solid media. S. aureus CECT239 was grown in liquid media in the presence of para-coumaric acid at the indicated concentrations (above), and the minimum inhibitory concentration (MIC) was determined as the lowest concentrationof product that completely inhibited growth (measured by OD600). Below, the liquid cultures from the MIC experiment were plated to check for microbial growth in solid media, and the minimum microcidal concentration (MMC) was determined as the lowest concentration of product that inhibited growth (determined by lack of visible colonies). Data are represented as Mean ± Std and the statistical significance was calculated compared to the non-treated control and depicted as follows; **** p value < 0.0001.Figure 31 shows the microbial growth in liquid and solid media. S. aureus V329 was grown in liquid media in the presence of para-coumaric acid at the indicated concentrations (above), and the minimum inhibitory concentration (MIC) was determined as the lowest concentration of product that completely inhibited growth (measured by OD600). Below, the liquid cultures from the MIC experiment were plated to check for microbial growth in solid media, and the minimum microcidal concentration (MMC) was determined as the lowest concentration of product that inhibited growth (determined by lack of visible colonies). Data are represented as Mean ± Std and the statistical significance was calculated compared to the non-treated control and depicted as follows; **** p value < 0.0001.Figure 32 shows the microbial growth in liquid and solid media. S. epidermidis was grown in liquid media in the presence of para-coumaric acid at the indicated concentrations (above), and the minimum inhibitory concentration (MIC) was determined as the lowest concentration of product that completely inhibited growth (measured by OD600). Below, the liquid cultures from the MIC experiment were plated to check for microbial growth in solid media, and the minimum microcidal concentration (MMC) was determined as the lowest concentration of product that inhibited growth (determined by lack of visible colonies). Data are represented as Mean ± Std and the statistical significance was calculated compared to the non-treated control and depicted as follows; **** p value < 0.0001.Figure 33 shows the microbial growth in liquid and solid media. C. acnes was grown in liquid media in the presence of para-coumaric acid at the indicated concentrations (above), and the minimum inhibitory concentration (MIC) was determined as the lowest concentration of product that completely inhibited growth (measured by OD600). Below, the liquid cultures from the MIC experiment were plated to check for microbial growth in solid media, and the minimum microcidal concentration (MMC) was determined as the lowest concentration of product that inhibited growth (determined by lack of visible colonies). Data are represented as Mean ± Std and the statistical significance was calculated compared to the non-treated control and depicted as follows; ** p-value <0.01, **** p value < 0.0001.Figure 34 shows the microbial growth in liquid and solid media. M. furfur was grown in liquidmedia in the presence of para-coumaric acid at the indicated concentrations (above), and the minimum inhibitory concentration (MIC) was determined as the lowest concentration of product that completely inhibited growth (measured by OD600). Below, the liquid cultures from the MIC experiment were plated to check for microbial growth in solid media, and the minimum microcidal concentration (MMC) was determined as the lowest concentration of product that inhibited growth (determined by lack of visible colonies). Data are represented as Mean ± Std and the statistical significance was calculated compared to the non-treated control and depicted as follows; **** p value < 0.0001.Figure 35 shows the microbial growth in liquid and solid media. M. restricta was grown in liquid media in the presence of para-coumaric acid at the indicated concentrations (above), and the minimum inhibitory concentration (MIC) was determined as the lowest concentration of product that completely inhibited growth (measured by ODgoo). Below, the liquid cultures from the MIC experiment were plated to check for microbial growth in solid media, and the minimum microcidal concentration (MMC) was determined as the lowest concentration of product that inhibited growth (determined by lack of visible colonies). Data are represented as Mean ± Std and the statistical significance was calculated compared to the non-treated control and depicted as follows; **** p value < 0.0001.Figure 36 shows human cell viability upon treatment with products: zosteric acid (A); azelaic acid (B); benzoyl peroxide (C); selenium sulfide (D); and zinc pyrithione (E). Graphical representation of the results showing the cell viability of human keratinocytes after treatment with the products at the indicated dose ranges for 24 hours compared to the non-treated control. Astersks represent statistical significance as * for p < 0.05, **** for p < 0.0001.Figure 37 shows the determination of minimum inhibitory concentration for zosteric acid in C. acnes (A), benzoyl peroxide in C. acnes (B), azelaic acid in C. acnes (C); zosteric acid in M. furfur (D); zinc pyrithione in M. furfur (E); and selenium sulfide in M. furfur (F). MIC of the tested products in C. acnes and m. furfur. MIC was determined as the lowest concentration of product that completely inhibited growth in liquid media (measured by OD600). Data are represented as Mean + / - SEM and the statistical significance was calculated compared to the non-treated control and depicted as follows; * for p < 0.05, **** for p < 0.0001.Incorporation by reference

[0013] All publications, patents, and patent applications referred to herein are incorporated by reference to the same extent as if each individual publication, patent, or patent application was specifically and individually indicated to be incorporated by reference. In the event of a conflictbetween a term herein and a term in an incorporated reference, the term herein prevails and controls.Detailed Description

[0014] The features and advantages of the present invention is readily apparent to a person skilled in the art by the below detailed description of embodiments and examples of the invention with reference to the figures and drawings included herein.Definitions

[0015] The term "preventing" as used herein in the context of preventing a cosmetic condition refers to the proactive application or use of the composition to inhibit, deter, or stop the onset or occurrence of the specified topical condition before its manifestation on the subject. This implies that the composition can be applied to areas that may be susceptible to the condition, even if visible or noticeable symptoms are not yet present, to reduce the likelihood or potential of the condition's development or occurrence.

[0016] The term "alleviating" as used herein in the context of alleviating topical conditions with the specified composition, the term "alleviating" refers to the application or use of the composition to reduce, diminish, or relieve the severity, intensity, or discomfort associated with an already manifested topical condition on the subject. This implies that the composition can be applied to areas showing signs or symptoms of the condition with the intention of improving the condition's appearance, symptoms, or associated discomfort, without necessarily implying a complete cure or removal of the condition.

[0017] The term "biobased" as used herein is used to characterize biobased products wherein:

[0018] the total carbon content of the product is at least 30%, and

[0019] the carbon content of a renewable raw material (biobased) is at least 20%.

[0020] As recognized by the Circular Bio-based Europe Joint Undertaking (CBE Joint Undertaking) established in 2021, developing biobased materials is essential if the EU is to reach its climate targets as set out in the European Green Deal.

[0021] Both fossil and renewable raw materials consist mainly of carbon (C). Carbon occurs in several isotopes. Isotope 14C is radioactive and occurs naturally in all living organisms (plants, animals, etc) in a fixed relative concentration which is nearly identical to the relative 14C concentration in the atmosphere. At this concentration, the radioactivity level of 14C is 100%. Once an organism is no longer living, this concentration, and thus the radioactivity rate, decays with a half-life of approximately 5700 years. The radioactive 14C level of an unknown substance can therefore help determine how old the carbon contained in the substance is.

[0022] "Young" carbon (0 to 10 years) derived from renewable raw materials, such as plants or animals, has a relative isotope 14C concentration which is nearly identical to the relative 14C concentration in the atmosphere and the radioactive 14C level of such young carbon is thus about 100%.

[0023] "Old" carbon (millions of years) derived from synthetic or fossil (petrochemical) sources is greatly depleted from isotope 14C as the age of such synthetic and fossil sources far exceeds the halflife of isotope 14C which is approximately 5700 years. Hence, carbon derived from synthetic or fossil sources has a relative isotope 14C concentration around 0% and the radioactive 14C level of such old carbon is thus about 0%.

[0024] In one embodiment the term "radioactive 14C level" refer to the total radioactive 14C level of a given substance, product, or composition, as defined above.

[0025] The isotope 14C method may be used to determine the concentration of young (renewable) materials in comparison with the concentration of old (fossil) resources. The carbon content of a renewable raw material is referred to as the "biobased carbon content". The carbon content of a renewable raw material or the "biobased carbon content" may be determined as described below.

[0026] When measuring the biobased carbon content, the result may be reported as "% biobased carbon". This indicates the percentage carbon from "natural" (plant or animal by-product) sources versus "synthetic" or "fossil" (petrochemical) sources. For reference, 100 % biobased carbon indicates that a material is entirely sourced from plants or animal by-products and 0 % biobased carbon indicates that a material did not contain any carbon from plants or animal by-products. A value in between represents a mixture of natural and fossil sources.

[0027] Example: If a product has a radioactive 14C level of 80%, it means that the product consists of 80% renewable and 20% fossil carbon (C). In other words, the product is 80% biobased.

[0028] The analytical measurement may be cited as "percent modern carbon (pMC)". This is the percentage of 14C measured in the sample relative to a modern reference standard (NIST 4990C). The % Biobased Carbon content is calculated from pMC by applying a small adjustment factor for 14C in carbon dioxide in air today. It is important to note that all internationally recognized standards using 14C assume that the plant or biomass feedstocks were obtained from natural environments. pMC may be analysed by a standard test method, such as "ASTM D6866".Cosmetic uses

[0029] In one embodiment, cosmetic use of a composition is provided comprising a hydroxycinnamic acid or a derivative thereof for preventing and / or alleviating a topical condition on a subject. The utility of the hydroxycinnamic acid or a derivative thereof in a cosmetic setting is supported by the findingsof Example 1 of the present disclosure.

[0030] An important aspect of the present disclosure relates to the cosmetic use of the hydroxycinnamic acids disclosed herein. In particular, cosmetic use can be achieved in a context, such as but not limited to particular concentrations where the hydroxycinnamic acids are not bactericidal yet inhibit proliferation and / or adherence of the microbial organism. In one embodiment, the use inhibits adherence and / or proliferation of a microbial organism on the skin of the subject without affecting microbial growth of the microbial organism.

[0031] In one embodiment, the topical condition is a skin and / or a scalp condition.

[0032] In one embodiment, the skin condition is selected from the group consisting of: acne, rosacea, seborrheic dermatitis, tinea versicolor, and wrinkles.

[0033] In one embodiment, the skin condition is acne.

[0034] In one embodiment, the use alleviates and / or prevents one or more of: pimples, blackheads, and cysts.

[0035] In one embodiment, the scalp condition is selected from the group consisting of: dandruff, dry scalp, oily or greasy scalp, scalp folliculitis, alopecia areata, and scalp acne.

[0036] In one embodiment, the scalp condition is dandruff.Concentrations

[0037] In one embodiment, the use comprises applying the hydroxycinnamic acid or derivative thereof in a concentration of 0.1% or less to the skin, such as 0.009% or less, such as 0.009% or less, such as 0.008% or less, such as 0.007% or less, such as 0.006% or less, such as 0.005% or less, such as 0.004% or less, such as 0.003% or less, such as 0.002% or less, such as 0.001% or less. In the context of the present disclosure, unless stated otherwise, concentrations are provided in weight %, i.e. % w / w.

[0038] In one embodiment, the use comprises applying the hydroxycinnamic acid or derivative thereof in a concentration of from 0.001% to 0.1% to the skin, such as from 0.001% to 0.005%, such as from 0.005% to 0.01%, such as from 0.01% to 0.02%, such as from 0.02% to 0.03%, such as from 0.03% to 0.04%, such as from 0.04% to 0.05%, such as from 0.05% to 0.06%, such as from 0.06% to 0.07%, such as from 0.07% to 0.08%, such as from 0.08% to 0.09% such as from 0.09% to 0.1%.

[0039] In one embodiment, the use comprises applying the hydroxycinnamic acid or derivative thereof, for example zosteric acid in a concentration of from 0.5% to 1.5%, for example 1%. As demonstrated in Examples 2 and 3, the use of 1% zosteric acid for example in a shampoo or a serum has significant advantages in alleviating topical conditions such as acne and / or dandruff. In some embodiments, the cosmetic use comprises applying the hydroxycinnamic acid or derivative thereof,such as zosteric acid, in a concentration of 0.5% to 1.5%, such as 1.0%, wherein the skin condition is acne or dandruff, for example acne or for example dandruff.

[0040] In some embodiments, the use comprises applying the hydroxycinnamic acid or derivative thereof in a concentration of from 0.05% to 10% to the skin, such as from 0.05% to 1%, such as from 1% to 2%, such as from 2% to 3%, such as from 3% to 4%, such as from 4% to 5%, such as from 5% to 6%, such as from 6% to 7%, such as from 7% to 8%, such as from 8% to 9%, such as from 9% to 10%. In preferred embodiments, the hydroxycinnamic acid or derivative thereof applied in these concentrations is zosteric acid.

[0041] In some embodiments, the concentration is from 0.5% to 2%, such as 1%.

[0042] In some embodiments, the microbial organism is M. restricta and the use comprises applying the hydroxycinnamic acid or derivative thereof, for example coumaric acid, such as para-coumaric acid, in a concentration of from 0.001% to 0.1% to the skin, such as from 0.001% to 0.005%, such as from 0.005% to 0.01%, such as from 0.01% to 0.02%, such as from 0.02% to 0.03%, such as from 0.03% to 0.04%, such as from 0.04% to 0.05%, such as from 0.05% to 0.06%, such as from 0.06% to 0.07%, such as from 0.07% to 0.08%, such as from 0.08% to 0.09%, such as from 0.09% to 0.1%.

[0043] In some embodiments, the microbial organism is S. epidermidis and the use comprises applying the hydroxycinnamic acid or derivative thereof in a concentration of from 0.001% to 0.05% to the skin, such as from 0.001% to 0.002%, such as from 0.002% to 0.003%, such as from 0.003% to 0.004%, such as from 0.004% to 0.005%, such as from 0.005% to 0.006%, such as from 0.006% to 0.007%, such as from 0.007% to 0.008%, such as from 0.008% to 0.009%, such as from 0.009% to 0.01%, such as from 0.01% to 0.02%, such as from 0.02% to 0.03%, such as from 0.03% to 0.04%, such as from 0.04% to 0.05%.Microbial organisms

[0044] Microorganisms like Malassezia furfur (M. furfur), Malassezia restricta (M. restricta), Staphylococcus aureus (S. aureus), Cutibacterium acnes (C. acnes), and Staphylococcus epidermidis (S. epidermidis) are known to play pivotal roles in a range of skin disorders or cosmetic conditions.

[0045] In one embodiment, above concentrations are applied where the microbial organism is selected from the group consisting of: M. furfur, M. restricta, or S. aureus, such as S. aureus CECT239 or V329, and S. epidermidis, and C. acnes.

[0046] In some embodiments, the microbial organism is part of a community of microbial organisms comprising a plurality of microbial organisms.

[0047] In one embodiment, the microbial organism is M. furfur and the use comprises applying the hydroxycinnamic acid or derivative thereof in a concentration of from 0.001% to 0.1% to the skin, suchas from 0.001% to 0.005%, such as from 0.005% to 0.01%, such as from 0.01% to 0.02%, such as from 0.02% to 0.03%, such as from 0.03% to 0.04%, such as from 0.04% to 0.05%, such as from 0.05% to 0.06%, such as from 0.06% to 0.07%, such as from 0.07% to 0.08%, such as from 0.08% to 0.09%, such as from 0.09% to 0.1%.

[0048] In one embodiment, the microbial organism is M. restricta and the use comprises applying the hydroxycinnamic acid or derivative thereof in a concentration of from 0.001% to 0.05% to the skin, such as from 0.001% to 0.005%, such as from 0.005% to 0.01%, such as from 0.01% to 0.02%, such as from 0.02% to 0.03%, such as from 0.03% to 0.04%, such as from 0.04% to 0.05%.

[0049] In one embodiment, the microbial organism is S. aureus and the use comprises applying the hydroxycinnamic acid or derivative thereof in a concentration of from 0.001% to 0.1% to the skin, such as from 0.001% to 0.005%, such as from 0.005% to 0.01%, such as from 0.01% to 0.02%, such as from 0.02% to 0.03%, such as from 0.03% to 0.04%, such as from 0.04% to 0.05%, such as from 0.05% to 0.06%, such as from 0.06% to 0.07%, such as from 0.07% to 0.08%, such as from 0.08% to 0.09%, such as from 0.09% to 0.1%.

[0050] In one embodiment, the microbial organism is C. acnes and the use comprises applying the hydroxycinnamic acid or derivative thereof in a concentration of from 0.001% to 0.01% to the skin, such as from 0.001% to 0.002%, such as from 0.002% to 0.003%, such as from 0.003% to 0.004%, such as from 0.004% to 0.005%, such as from 0.005% to 0.006%, such as from 0.006% to 0.007%, such as from 0.007% to 0.008%, such as from 0.008% to 0.009%, such as from 0.009% to 0.01%.Hydroxycinnamic acid or derivatives thereof

[0051] In one embodiment, the cosmetic or therapeutic use according to the present disclosure comprises a hydroxycinnamic acid or derivative thereof, including any salt thereof. In particular, the hydroxycinnamic acid or derivative thereof can be in a salt form, such as an alkali metal salt form. In one embodiment, the hydroxycinnamic acid or derivative thereof is a sodium salt or a potassium salt.

[0052] In some embodiments, the hydroxycinnamic acid or derivative thereof is zosteric acid and the salt is sodium or potassium, such as monosodium or monopotassium. In some embodiments, the salt is a dipotassium or disodium salt.

[0053] In some embodiments, said hydroxycinnamic acid or a derivative thereof is:, or a salt thereof, wherein Ri, R2 and R3 independently are selected from the group consisting of hydrogen (H), hydroxyl (OH), Ci-6-alkyl and Ci-g-alkoxy, -O-SO2-OR5, wherein R5is selected from the group consisting of: hydrogen and Ci-g-alkyl; provided that at least one of Ri, R2 and R3 is hydroxyl (OH) or -O-SO2-OR5, and R4is selected from the group consisting of hydrogen (H) and Ci-g-alkyl.

[0054] In some embodiments, R2 is -O-SO2-OR5. In some embodiments, R2 is -O-SO2-OR5 and R5is hydrogen.

[0055] In some embodiments, R2 is -OH.

[0056] In some embodiments, the hydroxycinnamic acid or derivative thereof is zosteric acid.

[0057] In some embodiments, the hydroxycinnamic acid or derivative thereof is coumaric acid, such as para-coumaric acid.Compositions

[0058] In some embodiments, the composition comprises the hydroxycinnamic acid or derivative thereof in a concentration from about 0.1%w / w to about 10%w / w, water and a preservative.

[0059] In some embodiments, the composition comprises the hydroxycinnamic acid or derivative thereof with a trans / c / s-ratio of at least 90:10, such as at least 91:9, such as at least 92:8, such as at least 93:7, such as at least 94:6, such as at least 95:5, such as at least 96:4, such as at least 97:3, such as at least 98:2, such as at least 99:1, for example 100:0.

[0060] In some embodiments, the composition is a biobased composition.

[0061] In some embodiments, the composition comprises at least 20% biobased carbon, such as at least 30% biobased carbon, such as at least 40% biobased carbon, such as at least 50% biobased carbon, such as at least 60% biobased carbon, such as at least 70% biobased carbon, such as at least 75% biobased carbon, such as at least 80% biobased carbon, such as at least 85% biobased carbon, such as at least 90% biobased carbon, such as at least 95% biobased carbon, such as 100% biobased carbon.

[0062] In some embodiments, the composition comprises from 20% to 100% biobased carbon, such as from 30% to 100% biobased carbon, such as from 40% to 100% biobased carbon, such as from 50% to 100% biobased carbon, such as from 60% to 100% biobased carbon, such as from 70% to 100%biobased carbon, such as from 75% to 100% biobased carbon, such as from 80% to 100% biobased carbon, such as from 85% to 100% biobased carbon, such as from 90% to 100% biobased carbon, such as from 95% to 100% biobased carbon, such as 100% biobased carbon.

[0063] In some embodiments, a composition is provided comprising a hydroxycinnamic acid or derivative thereof according to the formula:, or a salt thereof, wherein Ri, Rj and R3 independently are selected from the group consisting of hydrogen (H), hydroxyl (OH), Ci-6-alkyl and Ci-g-alkoxy, -O-SO2-OR5, wherein R5is selected from the group consisting of: hydrogen and Ci.g-alkyl; provided that at least one of Ri, R2 and R3 is hydroxyl (OH) or -O-SO2-OR5, and R4is selected from the group consisting of hydrogen (H) and Ci-g-alkyl. In some embodiments, R2 is -OH.

[0064] In some embodiments, the composition is formulated for topical administration. In some embodiments, the composition is in the form of a serum, a shampoo, a cream, a lotion, a gel, an ointment, a foam, a spray, a patch, an oil, a balm, a mask, a soap, or a medicated wipe. In some embodiments, the composition comprises 1% zosteric acid and is in the form of a serum, a shampoo, a cream, a lotion, a gel, an ointment, a foam, a spray, a patch, an oil, a balm, a mask, a soap, or a medicated wipe. In particular embodiments, the composition is in the form of a serum or a shampoo. In particular embodiments, the composition comprises from 0.5% to 1.5% zosteric acid and is in the form of a serum or a shampoo.

[0065] In some embodiments, a formulation is provided for topical administration comprising a hydroxycinnamic acid or derivative thereof as defined herein, for example zosteric acid, in a concentration of from 0.5% to 1.5%, such as 1%, wherein the formulation is in the form of a serum or a shampoo.Cosmetic product

[0066] In some embodiments, a cosmetic product is provided comprising the composition as disclosed herein. In some embodiments, the cosmetic product is provided wherein the cosmetic product is selected from the group consisting of: a shampoo, a conditioner, such as a hair conditioner, a serum, a cream, pads, such as spot pads, a lotion, a gel, a soap, a deodorant, a body wash product,and a spray, such as a scalp or skin spray.

[0067] In some embodiments, the present disclosure provides a shampoo comprising the hydroxycinnamic acid or derivative thereof in a concentration of from 1 to 5%, such as a wherein the hydroxycinnamic acid or derivative thereof is zosteric acid or para-coumaric acid, for example wherein the concentration is 1%, 2%, 3%, 4%, or 5%.

[0068] In some embodiments, the present disclosure provides a conditioner comprising the hydroxycinnamic acid or derivative thereof in a concentration of from 1 to 5%, such as a wherein the hydroxycinnamic acid or derivative thereof is zosteric acid or para-coumaric acid, for example wherein the concentration is 1%, 2%, 3%, 4%, or 5%.

[0069] In some embodiments, the present disclosure provides a serum comprising the hydroxycinnamic acid or derivative thereof in a concentration of from 1 to 10%, such as a wherein the hydroxycinnamic acid or derivative thereof is zosteric acid or para-coumaric acid, for example wherein the concentration is 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, or 10%.

[0070] In some embodiments, the present disclosure provides a cream comprising the hydroxycinnamic acid or derivative thereof in a concentration of from 1 to 10%, such as a wherein the hydroxycinnamic acid or derivative thereof is zosteric acid or para-coumaric acid, for example wherein the concentration is 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, or 10%.

[0071] In some embodiments, the present disclosure provides a lotion comprising the hydroxycinnamic acid or derivative thereof in a concentration of from 1 to 10%, such as a wherein the hydroxycinnamic acid or derivative thereof is zosteric acid or para-coumaric acid, for example wherein the concentration is 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, or 10%.

[0072] In some embodiments, the present disclosure provides a gel comprising the hydroxycinnamic acid or derivative thereof in a concentration of from 1 to 5%, such as a wherein the hydroxycinnamic acid or derivative thereof is zosteric acid or para-coumaric acid, for example wherein the concentration is 1%, 2%, 3%, 4%, or 5%.

[0073] In some embodiments, the present disclosure provides a gel comprising the hydroxycinnamic acid or derivative thereof in a concentration of from 1 to 5%, such as a wherein the hydroxycinnamic acid or derivative thereof is zosteric acid or para-coumaric acid, for example wherein the concentration is 1%, 2%, 3%, 4%, or 5%.

[0074] In some embodiments, the present disclosure provides a spray comprising the hydroxycinnamic acid or derivative thereof in a concentration of from 1 to 15%, such as a wherein the hydroxycinnamic acid or derivative thereof is zosteric acid or para-coumaric acid, for example wherein the concentration is 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, or 15%.

[0075] In some embodiments, the cosmetic product further comprises one or more additionalcosmetic agents selected from the group consisting of: benzoyl peroxide, salicylic acid, alpha hydroxy acids, retinoids, ketoconazole, arbutin, kojic acid, vitamin C, and licorice extract.

[0076] Any of these embodiments can be used for the formulation for topical administration referred to herein.Therapy

[0077] As disclosed herein, whether the use is cosmetic or therapeutic can depend on factors such as the applied concentration of the hydroxycinnamic acid or derivative thereof, or on whether a condition is recognized as a cosmetic or pathological condition in particular social cultures. In some aspects, the present disclosure provides cosmetic use and in other aspects, the present disclosure provides a therapy.

[0078] In some embodiments, a composition is provided comprising hydroxycinnamic acid or a derivative thereof for use in the treatment of a skin disorder.

[0079] In some embodiments, the skin disorder results from a skin and / or a scalp condition.

[0080] In some embodiments, the skin disorder is selected from the group consisting of: acne vulgaris, rosacea, seborrheic dermatitis, tinea versicolor, skin aging, atopic dermatitis, psoriasis, and eczema.

[0081] In some embodiments, the skin disorder is acne vulgaris.

[0082] In some embodiments, the treatment alleviates and / or reduces one or more of the symptoms selected from the group consisting of: pimples, blackheads, cysts, inflammation, erythema, and scarring.

[0083] In some embodiments, the scalp disorder is selected from the group consisting of: seborrheic dermatitis, scalp psoriasis, folliculitis, alopecia areata, telogen effluvium, and scalp acne.

[0084] In some embodiments, the scalp disorder is seborrheic dermatitis. In some embodiments, the scalp disorder is alopecia areata.

[0085] In some embodiments, the skin disorder results from a microbial infection.

[0086] In some embodiments, the microbial infection is caused by one or more microorganisms selected from the group consisting of: M. furfur, M. restricta, S. aureus, C. acnes, and S. epidermidis.

[0087] In some embodiments, the skin disorder is tinea versicolor or seborrheic dermatitis, for example caused by M. furfur.

[0088] In some embodiments, the skin disorder is acne vulgaris or folliculitis, for example caused by C. acnes. In some embodiments, the skin disorder is atopic dermatitis, for example caused by S. epidermidis. In some embodiments, the skin disorder is impetigo or folliculitis, for example caused by S. aureus strains CECT239 or V329.

[0089] In some embodiments, the microbial organism is M. furfur and the use comprises applying the hydroxycinnamic acid or derivative thereof in a concentration of from 0.5% to 10% to the skin, such as from 0.5% to 1%, such as from 1% to 2%, such as from 2% to 3%, such as from 3% to 4%, such as from 4% to 5%, such as from 5% to 6%, such as from 6% to 7%, such as from 7% to 8%, such as from 8% to 9%, such as from 9% to 10%.

[0090] In some embodiments, the microbial organism is M. restricta and the use comprises applying the hydroxycinnamic acid or derivative thereof in a concentration of from 0.1% to 10% to the skin, such as from 0.1% to 1%, such as from 1% to 2%, such as from 2% to 3%, such as from 3% to 4%, such as from 4% to 5%, such as from 5% to 6%, such as from 6% to 7%, such as from 7% to 8%, such as from 8% to 9%, such as from 9% to 10%.

[0091] In some embodiments, the microbial organism is S. aureus and the use comprises applying the hydroxycinnamic acid or derivative thereof in a concentration of from 0.5% to 10% to the skin, such as from 0.5% to 1%, such as from 1% to 2%, such as from 2% to 3%, such as from 3% to 4%, such as from 4% to 5%, such as from 5% to 6%, such as from 6% to 7%, such as from 7% to 8%, such as from 8% to 9%, such as from 9% to 10%.

[0092] In some embodiments, the microbial organism is C. acnes and the use comprises applying the hydroxycinnamic acid or derivative thereof in a concentration of from 0.05% to 10% to the skin, such as from 0.05% to 1%, such as from 1% to 2%, such as from 2% to 3%, such as from 3% to 4%, such as from 4% to 5%, such as from 5% to 6%, such as from 6% to 7%, such as from 7% to 8%, such as from 8% to 9%, such as from 9% to 10%.

[0093] In some embodiments, the microbial organism is S. epidermidis and the use comprises applying the hydroxycinnamic acid or derivative thereof in a concentration of from 0.05% to 10% to the skin, such as from 0.05% to 1%, such as from 1% to 2%, such as from 2% to 3%, such as from 3% to 4%, such as from 4% to 5%, such as from 5% to 6%, such as from 6% to 7%, such as from 7% to 8%, such as from 8% to 9%, such as from 9% to 10%.ExamplesMaterials and methods

[0094] Chemicals used in the examples herein, e.g. for buffers and substrates, are commercial products of at least reagent grade.Example 1: Ex vivo evaluation of microbial adherence on pig skin explants

[0095] The present example evaluates the effect of zosteric acid on microbial adherence. In particular, the present example studies the concentration dependence of zosteric acid on its cosmetictopical applicability.Materials & methods

[0096] In vitro viability assay and ex vivo adherence assay in pig skin explants with different strains of Staphylococcus aureus, Staphylococcus epidermidis, Cutibacterium acnes, Malasssezia furfur and Malassezia restricta.

[0097] Microscope, incubator, statistical analysis software, laminar flow hood for microorganisms, micropipettes, pipettes, pro-pipette, rack, punch biopsy instrument, vortex, orbital shaker with regulated temperature, spectrophotometer and consumables.

[0098] Distilled water (Braun), Phosphate buffered saline (Sigma-Aldrich), DMSO (Sigma- Aldrich), Ethanol (Sigma-Aldrich), Oxoid CM0149 medium (Reinforced Clostridial medium), Nutrient broth / agar I medium, OXOID CM0920 medium, pig skin explants, anaerobic jar and anaerobiosis atmosphere generator.

[0099] Procedure: The strains used in this example are listed as follows:• Malassezia furfur (ATCC 44344), dandruff-associated species• Malassezia restricta (ATCC MYA-4611), dandruff-associated species.• Staphylococcus aureus CECT 239 (clinical isolate), atopic dermatitis-associated species.• Staphylococcus aureus V329 (high biofilm production strain), atopic dermatitis- associated species.• Staphylococcus epidermidis (CECT231), commensal species of the skin microbiota.• Cutibacterium acnes (CECT5684), acne-associated species.• Staphylococcus spp were grown in broth / agar Nutrient Broth I medium for 24 h at 37 °C. C. acnes was grown in broth / agar Reinforced Clostridial medium for 48-72 h at 37 °C in anaerobic conditions, using an anaerobic jar and an anaerobic atmosphere generator. Malasssezia spp were grown in broth / agar OXOID CM0920 medium for 96 h at 30 °C.

[0100] For MIC determination, the strains were grown as detailed above and diluted to an initial OD600 of 0.01 in a 96-well plate containing Zostreric acid at different concentrations (1, 0.5, 0.1, 0.05, 0.01, 0.005, 0.001 and 0.0005%). After 24 h (Staphylococcus spp), 48 h (Cutibacterium acnes) or 96 h (Malassezia spp), the microbial growth was measured by OD600 in a spectrophotometer to determine the minimum concentration necessary to inhibit growth in the liquid culture medium (MIC). To establish the MMC, 10 pl of medium were removed from each well and plated on appropriate agar media; after 24 h (Staphylococcus spp), 48 h (Cutibacterium acnes) or 96 h (Malassezia spp) ofincubation, the plates were checked for colonies and the MMC was established as the minimum concentration of product necessary to completely inhibit microbial growth on the agar plates (no visible colonies).Ex vivo adherence assay

[0101] Pig skin explants were obtained from a meat-processing facility, and then cleaned and sterilized. Serial dilutions of the product were prepared (1, 0.5, 0.1, 0.05, 0.01, 0.005, 0.001 and 0.0005%) and applied to the surface of the skin explant in sterile conditions, and then incubated at room temperature for 1 hour (h) to allow penetration of the product in the skin. For the microbial cell preparation, Staphylococcus spp were grown in broth / agar Nutrient Broth I medium for 24 h at 37 °C; C. acnes was grown in broth / agar Reinforced Clostridial medium for 48-72 h at 37 °C in anaerobic conditions, using an anaerobic jar and an anaerobic atmosphere generator, and Malasssezia spp were grown in broth / agar OXOID CM0920 medium for 96 h at 30 °C.

[0102] Strains were grown on agar plates and a single colony from a pure culture was used to inoculate appropriate liquid media, and then diluted at a density of 109 cfu / ml and applied to the surface of the treated skin explants. A condition inoculating microbial cells to non-treated skin explants was included as negative control. After 1 h (to evaluate the adherence to the skin explant) or 24 h (to evaluate the proliferation on the skin explant), the skin explants were thoroughly washed with sterile PBS, and a punch biopsy was taken with specialized equipment. The microbial cells adhered to the biopsy sample were quantified by the drop plate method. Data were statistically analyzed.

[0103] For MIC determination, 8 technical replicates were performed. For MMC determination, at least 3 technical replicates were performed. For the adherence assays, 3 technical replicates per condition were used. All data were statistically analysed using a One-way ANOVA test. Statistical significance was set at p < 0.05, 95% of confidence. Graphical results were represented as mean ± SEM (Standard Error of the Mean).Results

[0104] Minimal inhibitory (MIC) and microcidal (MMC) concentration results: The results of the MIC and MMC assays for Zosteric acid are summarized below for each microbial strain:The MIC of Zosteric acid in M. furfur is 1%, although growth was reduced when the product was used at 0.5% (Figure 1).The MMC of Zosteric acid in M. furfur is 1% (Figure 1).The MIC of Zosteric acid in M. restricta is 1%, although growth was reduced when the product was used at 0.5% and 0.1% (Figure 2).The MMC of Zosteric acid in M. restricta is 1% (Figure 2).The MIC of Zosteric acid in S. aureus CECT239 is 1%, although growth was reduced when the product was used at 0.5% and 0.1% (Figure 3).The MMC of Zosteric acid in S. aureus CECT239 is 1% (Figure 3).The MIC of Zosteric acid in S. aureus V329 is 1%, although growth was reduced when the product was used at 0.5%, 0.1%, 0.05% and 0.01% (Figure 4).The MMC of Zosteric acid in S. aureus V329 is 1% (Figure 4).The MIC of Zosteric acid in S. epidermidis is 1%, although growth was reduced when the product was used at 0.5% and 0.1% (Figure 5).The MMC of Zosteric acid in S. epidermidis is 1% (Figure 5).The MIC of Zosteric acid in C. acnes is 0.5%, although growth was reduced when the product was used at 0.5%, 0.1% and 0.05% (Figure 6).The MMC of Zosteric acid in C. acnes is 1%. Interestingly, Zosteric acid used at 0.5% inhibited the growth in liquid media, but bacteria were still viable at this concentration, evidenced by the growth on solid media (Figure 6).

[0105] Ex vivo adherence assay: The results of the anti-microbial adherence effect of Zosteric acid in the ex vivo pig skin model are summarized below for each microbial strain.M. furfur cells were seeded on product-treated pig skin explants and incubated for 1 hour to allow adherence to the skin surface. Zosteric acid decreased the adherence of M. furfur to the pig skin explant when used at concentrations ranging from 1% to 0.05% (Figure 7). Among all these concentrations, Zosteric acid at 0.1% or 0.05% inhibited adherence without affecting the microbial growth (Figure 7).M. furfur cells were seeded on product-treated pig skin explants and incubated for 24 hours to allow proliferation on the skin surface. None of the concentrations of Zosteric acid decreased the proliferation of M. furfur on the pig skin explant in these conditions (Figure 8). M. restricta cells were seeded on product-treated pig skin explants and incubated for 1 hour to allow adherence to the skin surface. Zosteric acid decreased the adherence of M. restricta to the pig skin explant when used at concentrations ranging from 1% to 0.01% (Figure 9). Among all these concentrations, Zosteric acid at 0.05% or 0.01% inhibited adherence without affecting the microbial growth (Figure 9).M. restricta cells were seeded on product-treated pig skin explants and incubated for 24 hours to allow proliferation on the skin surface. Zosteric acid decreased the proliferation of M. restricta on the pig skin explant when used at concentrations ranging from 1% to 0.01% (Figure10). Among all these concentrations, Zosteric acid at 0.05% or 0.01% inhibited proliferation without affecting microbial growth (Figure 10).S. aureus CECT239 cells were seeded on product-treated pig skin explants and incubated for 1 hour to allow adherence to the skin surface. Zosteric acid decreased the adherence of S. aureus CECT239 to the pig skin explant when used at concentrations ranging from 1% to 0.1% (Figure 11). Among all these concentrations, Zosteric acid at 0.1% inhibited adherence affecting only marginally the microbial growth (Figure 11).S. aureus CECT239 cells were seeded on product-treated pig skin explants and incubated for 24 hours to allow proliferation on the skin surface. Zosteric acid decreased the proliferation of S. aureus CECT239 on the pig skin explant when used at concentrations ranging from 1% to 0.1% (Figure 12). Among all these concentrations, Zosteric acid at 0.1% inhibited proliferation affecting only marginally the microbial growth (Figure 12).S. aureus V329 cells were seeded on product-treated pig skin explants and incubated for 1 hour to allow adherence to the skin surface. Zosteric acid decreased the adherence of S. aureus V329 to the pig skin explant when used at concentrations ranging from 1% to 0.05% Figure 13). However, all these concentrations were shown to decrease the growth of S. aureus V329 (Figure 13).S. aureus V329 cells were seeded on product-treated pig skin explants and incubated for 24 hours to allow proliferation on the skin surface. Zosteric acid decreased the proliferation of S. aureus V329 on the pig skin explant when used at concentrations ranging from 1% to 0.05% (Figure 14). However, all these concentrations were shown to decrease the growth of S. aureus V329 (Figure 14).S. epidermidis cells were seeded on product-treated pig skin explants and incubated for 1 hour to allow adherence to the skin surface. Zosteric acid decreased the adherence of S. epidermidis to the pig skin explant when used at concentrations ranging from 1% to 0.1% (Figure 15). However, all these concentrations were shown to decrease the growth of S. epidermidis (Figure 15).S. epidermidis cells were seeded on product-treated pig skin explants and incubated for 24 hours to allow proliferation on the skin surface. Zosteric acid decreased the proliferation of S. epidermidis on the pig skin explant when used at concentrations ranging from 1% to 0.1% (Figure 16). However, all these concentrations were shown to decrease the growth of S. epidermidis (Figure 16).C. acnes cells were seeded on product-treated pig skin explants and incubated for 1 hour to allow adherence to the skin surface. Zosteric acid decreased the adherence of C. acnes to thepig skin explant when used at concentrations ranging from 1% to 0.01% (Figure 17). Among all these concentrations, Zosteric acid at 0.01% inhibited adherence without affecting the microbial growth (Figure 17).C. acnes cells were seeded on product -treated pig skin explants and incubated for 24 hours to allow proliferation on the skin surface. Zosteric acid decreased the proliferation of C. acnes on the pig skin explant when used at concentrations ranging from 1% to 0.1% (Figure 18). However, all these concentrations were shown to decrease the growth of C. acnes (Figure 18).

[0106] In summary, for all tested strains, the minimum microbicidal concentration (MMC) of Zosteric acid is 1%. Its minimum inhibitory concentration (MIC) is l% for most strains, except for C. acnes which has an MIC of 0.5%. Regarding microbial adherence to pig skin explants, Zosteric acid demonstrated varied efficacies:

[0107] For M. furfur, concentrations between 1% and 0.05% decreased adherence, with 0.1% or 0.05% optimally inhibiting adherence without affecting microbial growth.

[0108] M. restricta showed decreased adherence and proliferation between 1% and 0.01%, optimally at 0.05% or 0.01% without hampering microbial growth.

[0109] S. aureus CECT239 had decreased adherence and proliferation between 1% and 0.1%, with 0.1% being most effective with only marginal growth impact.

[0110] For both S. aureus V329 and S. epidermidis, concentrations ranging from 1% to 0.05% and 1% to 0.1% respectively led to reduced adherence and proliferation, but they also hindered microbial growth.

[0111] C. acnes had decreased adherence with concentrations between 1% to 0.01%, optimally at 0.01% without growth impact. However, for its proliferation, concentrations from 1% to 0.1% were shown to decrease its growth.Conclusions

[0112] The present example demonstrates that zosteric acid can be applied in concentrations effective toward inhibiting adherence and / or proliferation of a microbial organism on the skin of a subject without affecting microbial growth of the microbial organism. These results demonstrate a utility of zosteric acid and related hydroxycinnamic acids against cosmetic disturbances caused by selected microbial organisms, such as M. furfur, M. restricta, S. aureus, S. epidermidis, and C. acnes, for example relevant in prevention or alleviation of acne. The present examples further demonstrates that at some concentrations, zosteric acid can also be used to inhibit microbial growth of some microbial organisms.Example 2: Clinical evaluation of shampoo with 1% zosteric acid in 20 volunteers

[0113] The present example evaluates the effect of shampoo with 1% zosteric acid in the scalp after application in 20 volunteers, as well as to check the compatibility and acceptability of the product.Materials & MethodsProduct tested

[0114] The product tested was a shampoo formulated with 1% zosteric acid. The product was stored at room temperature and delivered to the volunteers before the start of the treatment.Sebumeter assessment

[0115] For more than 30 years the Sebumeter® has provided the worldwide most used method to determine the sebum level of the skin surface reproducibly and accurately, as well as on scalp and hair. This is documented by the numerous mentions in the scientific literature in which the terms "sebumetry" and sebum measurements come together. Sebumeter function is based on grease spot photometry. The mat tape of the Sebumeter® SM 815 is brought into contact with skin or hair (Figure 19). It becomes transparent according to the sebum on the surface of the measurement area. Then, the tape is inserted into the aperture of the device and the transparency is measured by a photocell. The light transmission represents the sebum content. Five measurements were performed for each volunteer at each of the time points.Expert evaluation scale

[0116] The Expert Evaluation Scales were carried out to subjectively assess the prevalence and severity of dandruff in the assay. In vivo visual evaluations are widely used in multiple cosmetic and dermatologic applications. For this study, grading scales of dandruff was carried out by the lab technical staff by virtually dividing the scalp into 4 sections and evaluating the dandruff content in each one of them, according to reference graphic scales and under standardized lighting conditions. Each section was rated, using a score from 0 to 5 (Figure 20). A final score was obtained by averaging the score of all four sections. Also, 1 macroscopic image and 3 microscopic images (using a Digital Microscope) of the scalp were taken at each timepoint (DO and D28).Self-assesment questionnaire

[0117] The efficacy of the treatment was subjectively evaluated by a use test (self-assessment questionnaire), answered by each of the volunteers who completed the study (28 days). For the selfassessment questionnaires, opinions are given according to parameters from 1 to 5, (1 = Strongly Disagree, 2 = Disagree, 3 = Neutral, 4 = Agree 5 =Strongly agree). For positive impressions, satisfaction is considered when volunteers scored parameters from 4 to 5.Procedure

[0118] The product was self- applied by the volunteers as indicated. In this study, 20 volunteers were submitted to treatment with shampoo with 1% zosteric acid. Sebum level of the scalp skin surface was evaluated with sebumeter. Dandruff severity was evaluated by using clinical scales. Additionally, cosmetic efficacy and consumer opinion were evaluated by a use test at the end of the study, after 28 days. All data were statistically analysed. The study was performed under dermatological surveillance. Use conditions

[0119] The product was self-applied by the volunteers following the client instructions:Apply every 2 days. Wet hair with water and apply an adequate amount of shampoo. Massage and leave for 3-5 minutes. Rinse with plenty of water.Avoid contact with eyes. If contact occurs, rinse thoroughly with cool water.Keep out of reach of children.Keep in a cool dry place.Panel

[0120] The panel represents the susceptible population to use the product.Inclusion criteria were:Male or females aged between 18-70.Presence of oily dandruff hair.Last participation in clinical study, at least one month before the start of this experiment.Subjects who have washed her / his hair at least 48 hours before the measurement.Understanding and signature of Informed ConsentOn the other hand, the criteria of exclusion were:Allergy or reactivity to some of the components of the product, or a product with similar category than tested one.Forecast of change of routine or relevant way of life, during the period of studySubjects with alopecia.Subjects who have used anti-dandruff shampoo during the week before the study begins.Nursing, pregnant, or planning to become pregnant during the study according to subject self-report. In-use relevant pharmacological or hormonal treatment.Checking of the acceptability

[0121] The subjects were requested to note every day any reaction observed, and sensation of discomfort felt. An examination of the experimental area under standard daylight source was performed by the responsible technician, the same days of the technical measurements. Togetherwith the clinical examinations performed during the treatment, each subject was questioned by the responsible technician about the possible sensations of discomfort they felt, at the end of the study.Consumption control

[0122] Consumption control was carried out to verify that volunteers follow the guidelines and apply the treatment. This value is used for evaluating the clinical adherence, according to the client's application protocol.Statistical analysis

[0123] For the evaluation of sebum five repeated measurements were performed on the scalp of each volunteer and dandruff. For dandruff analysis different images were used, and one experimental value was obtained from the region of interest (ROI) selected, for each timepoint.For statistical analysis, all data collected before (DO) and after treatment (D28) were subjected to the normality test using the Shapiro-Wilk method (Shapiro, 1965). The following methods were then applied to evaluate the statistical significance by pairs 0 vs 28. All those variables whose normality test result was positive (parametric variable) were analyzed using the paired t-test method (David, 1997). All those variables whose normality test result was not positive (non-parametric) were analyzed using the paired Wilcoxon method (Wilcoxon, 1959). In the report, the difference in percentage of the normalized data is plotted with the error bars indicating the standard error of the mean (SEM). For normalization, the technical values obtained before (DO) and after treatment are relativized to the basal values before treatment (DO) and expressed as a percentage.ResultsAcceptability assessment

[0124] 100% (n=20) of volunteers showed acceptance and skin / ocular compatibility, because they did not manifest neither adverse symptom nor cutaneous reactions during the period of treatment or the days after.Good clinical adherence

[0125] Product containers were weighed before and after the treatment and the 100% (n=20) of volunteers showed good clinical adherence.Sebum levels

[0126] Results showed that shampoo with 1% zosteric acid decreased sebum levels by 38.80 ± 6.01 % after 28 days of treatment comparing with basal values. (Figure 21).Dandruff evaluation

[0127] Results showed that shampoo with 1% zosteric acid decreased dandruff by 39.62 ± 4.99 % after 28 days of treatment comparing with basal values (Figure 22).Self-assessment questionnaire

[0128] The efficacy of the treatment was subjectively evaluated by a use test (self-assessment questionnaire), answered by each of the volunteers who completed the study. For the self-assessment questionnaires, opinions are given according to parameters from 1 to 5, (1 = Strongly Disagree, 2 = Disagree, 3 = Neutral, 4 = Agree 5 =Strongly agree). For positive impressions, satisfaction is considered when volunteers scored parameters from 4 to 5. Results from the self-assessment questionnaire after 28 days of treatment with are shown in the following table, table 1 (Figure 29):Table 1. Results of self-assessment questionnaire after 28 days of treatment.

[0129] A relevant percentage of volunteers (> 80 %) considered that shampoo with 1% zosteric acid: Product has a pleasant texture.This product is non-irritating.The product decreases the sebum in their hair.The product gently cleanses the scalp.They are satisfied with the treatment received.- 1 -They would use the treatment again.They would recommend the treatment to a friend.

[0130] Results of treatment showed an overall acceptance average of 76 %. Specifically, positive evaluations (overall acceptance > 80 %) were obtained for 7 out of 16 evaluated parameters.Conclusions

[0131] The present example demonstrates that a shampoo with 1% zosteric acid significantly reduces levels of sebum on the scalp. As excessive sebum levels are correlated to a number of topical conditions, such as scalp conditions, the usage of 1% zosteric acid, such as in the form of a shampoo, has impactful potential in alleviating topical conditions. Examples of topical conditions that would benefit from such usage include dandruff, seborrheic dermatitis, folliculitis, scalp acne, and greasy scalp. In particular, managing the cosmetic appearances of these conditions, such as dandruff, is important to the subjects suffering from these conditions.Example 3: Clinical evaluation of serum with 1% zosteric acid against acne in 20 volunteers

[0132] The present example evaluates the effect of serum with 1% zosteric acid against acne after topical application in 20 volunteers for 28 days, as well as to check the compatibility and acceptability of cosmetic products, after application under the normal conditions of use.Materials & MethodsProduct tested

[0133] The product tested was a serum formulated with 1% zosteric acid. The product was stored at room temperature and delivered to the volunteers before the start of the treatment.Acne evaluation

[0134] Acne analysis is conducted on 3D images captured using Visia-CR Primos technology, specifically with the Visia-CRP-5 capture system. The obtained files are in the .htom format. The VAM analysis program is utilized to analyze the DO and D28 3D files. From each analysis, values for height (mm), area (mm2 ), and volume (mm3 ) are obtained. The 3D analysis is performed using 3D PRIMOSCR digital fringe projection technology. During this analysis, a High Pass filter is applied, and subsequently, the images are superimposed with a flat surface to obtain values for area, volume, and height of the acne.Scaliness assessment

[0135] Corneofix® CF 20 is a special adhesive tape collecting corneocytes (flakes of dead cells). Thenumber, size, and thickness of the corneocytes indicate the desquamation level of the stratum corneum. Two Corneofix® samples were taken on cheek area of the volunteers at each of the time points. After the collection of the samples, they were digitized using Bio Blue Light Scanner which is an in-house developed device composed of an image acquisition system (high-resolution camera Dalsa TS 5 Mp + optical Schneider APO-Xenoplan) and a diffuse and indirect lighting system (domo type), emitting at 470 nm (blue light), as shown in Figure 23. The image acquisition system allows us to capture high resolution images at high speed, whereas the lightning system allows us to have a uniform, constant and without brightness or reflections illumination.

[0136] Image analysis was performed by using ImageJ software and quantifying the flakes on the tape. With the software, the level of gray color was evaluated, an indirect measurement of the skin scaliness level; as shown in Figure 24.

[0137] The greater the flaking, the higher the number would be in the grayscale color (close to white=255). On the other hand, the less flaking, the lower number would be in the grayscale color (close to black=0). In conclusion, the exfoliating effect can be determined by observing a decrease in the value in the grayscale when quantifying the Corneofix®.Standardized facial imaging

[0138] Standardized facial imaging are performed through Visia CR - Primos. The capture system used is Visia-CRP-5. The type of photos taken are the standard version. Three photos are taken: one in a 459angle to the left, a frontal photo, and another photo 459to the right.Self-Assessment questionnaire

[0139] The efficacy of the treatment was subjectively evaluated by a use test (self-assessment questionnaire), answered by each of the volunteers who completed the study (28 days). For the selfassessment questionnaires, opinions are given according to parameters from 1 to 5, (1 = Strongly Disagree, 2 = Disagree, 3 = Neutral, 4 = Agree 5 =Strongly agree). For positive impressions, satisfaction is considered when volunteers scored parameters from 4 to 5.Procedure

[0140] In this study, 20 volunteers underwent a 28-day facial treatment with serum with 1% zosteric acid. The effect of treatment was assessed through quantification of the acne using VISIA-CR, and skin scaliness was measured using Corneofix®. Measurements were taken both before (DO) and after 28 days (D28) from the commencement of the treatment. Furthermore, macroscopic images were captured before and after the treatment using Visia-CR. Volunteers also completed a self-assessment questionnaire at the end of the treatment (use test). The study was conducted under dermatological supervision.Use conditions

[0141] The product was self-applied by the volunteers following the client instructions:Apply twice a day (morning and evening) by massaging until completely absorbed.Discontinue use if signs of irritation appear.Avoid contact with eyes. If contact occurs, rinse thoroughly with cool water.Keep out of reach of children.Keep in a cool dry place.Panel

[0142] The panel represents the susceptible population to use the product.Inclusion criteria were:Females and male volunteers aged between 18 and 35Acne grade 3 to 5 according to expert scale (Figure 25).On the other hand, the criteria of exclusion were:Allergy or reactivity to some of the components of the product, or a product with a similar category than tested one.Recent surgery in the experimental area.Relevant cutaneous marks in the experimental areas, which could interfere with the measurements (scars, sunburns, etc.).In-use relevant pharmacological or hormonal treatment.Presence of skin diseases or melanomas.Forecast of change of routine or relevant way of life, during the period of study.Nursing, pregnant, or planning to become pregnant during the study according to subject self-report.Checking the acceptability

[0143] The subjects were requested to note every day any reaction observed, and sensation of discomfort felt. An examination of the experimental area under standard daylight source was performed by the responsible technician, the same days of the technical measurements. Together with the clinical examinations performed during the treatment, each subject was questioned by the responsible technician about the possible sensations of discomfort they felt, at the end of the study.Consumption control

[0144] Consumption control was carried out to verify that volunteers follow the guidelines and apply the treatment. This value is used for evaluating the clinical adherence, as the percentage of volunteers who follow the protocol and consume the estimated product to be consumed according to the client's application protocol.Statistical analysis

[0145] For measurements of acne, different images were used, and one experimental value was obtained from the region of interest (ROI) selected, for each timepoint. Three samples were taken with Corneofix and quantified at each timepoint. For statistical analysis, all data collected before (DO) and after 28 days (D28) of treatment were subjected to the normality test using the Shapiro-Wilk method (Shapiro, 1965). The following methods were then applied to evaluate the statistical significance by pairs 0 vs 28. All those variables whose normality test result was positive (parametric variable) were analyzed using the paired t-test method (David, 1997). All those variables whose normality test result was not positive (non-parametric) were analyzed using the paired Wilcoxon method (Wilcoxon, 1959). In the report, the difference in percentage of the normalized data is plotted with the error bars indicating the standard error of the mean (SEM) For normalization, the technical values obtained before (DO) and after treatment are relativized to the basal values before treatment (DO) and expressed as a percentage.ResultsAcceptability assessment

[0146] The 100% (n=20) of volunteers showed acceptance and skin compatibility, because they nor manifested adverse symptom or cutaneous reactions during the period of treatment or the days after.Good clinical adherence

[0147] Product containers were weighed before and after the treatment and the 100% (n=20) of volunteers showed good clinical adherence.Acne evaluation

[0148] Results showed that serum with 1% zosteric acid decreased acne area and acne volume by 7.28 ± 3.38% and 8.79 ± 3.63% after 28 days of treatment compared with basal values, respectively (Figure 26).Skin scaliness assessment

[0149] Results showed that serum with 1% zosteric acid did not significantly affect the level of skin scaliness after 28 days of treatment compared with basal values. (Figure 27).Self-Assessment questionnaireThe efficacy of the treatment was subjectively evaluated by a use test (self-assessment questionnaire), answered by each of the volunteers who completed the study. Results from the self-assessment questionnaire after 28 days of treatment of serum with 1% zosteric acid are shown in the following table 2 (and Figure 28):Table 2: Results of self-assessment questionnaire.

[0150] A relevant percentage of volunteers (> 80 %) considered that serum with 1% zosteric acid :The application of the product is easy. Rapid absorption of the product.This product is non-irritating.Results of treatment showed an overall acceptance average of 49 %.Conclusions

[0151] The present example demonstrates that serum with 1% zosteric acid effectively decreases acne area and volume, and that such serum is very easy to apply topically. Thus, topical conditions, in particular those presenting with acne, can be alleviated by 1% zosteric acid, for example in the form of a serum. Managing the cosmetic appearances of these conditions, such as acne, is important to the subjects suffering from these conditions.Example 4: In vitro evaluation of the minimum inhibitory concentration and microcidal concentration of pora-coumaric acid in bacteria and fungi relevant for cosmetics

[0152] The present example evaluates the efficacy of poro-coumaric acid to inhibit the proliferation of microbes relevant to the cosmetic segment. In particular, the present example evaluates the concentration at which poro-coumaric acid is effective in preventing the growth of Staphylococcus aureus, Staphylococcus epidermidis, Cutibacterium acnes, Malassezia furfur and Malassezia restricta.Materials & MethodsAnalytical equipment

[0153] Microscope, incubator, statistical analysis software, laminar flow hood for microorganisms, micropipettes, pipettes, pro-pipette, rack, vortex, orbital shaker with regulated temperature, spectrophotometer and consumables.Reagents

[0154] Distilled water (Braun), Phosphate buffered saline (Sigma-Aldrich), DMSO (Sigma-Aldrich), Ethanol (Sigma-Aldrich), Oxoid CM0149 medium (Reinforced Clostridial medium), Nutrient broth / agar I medium, OXOID CM0920 medium, anaerobic jar and anaerobiosis atmosphere generator.Procedure

[0155] Minimal inhibitory (MIC) and microcidal (MMC) concentration:The strains used in this study are listed as follows:Malassezia furfur (ATCC 44344), dandruff-associated species.Malassezia restricta (ATCC MYA-4611), dandruff-associated species.Staphylococcus aureus CECT 239 (clinical isolate), atopic dermatitis-associated species.Staphylococcus aureus V329 (high biofilm production strain), atopic dermatitis-associated species.Staphylococcus epidermidis (CECT231), commensal species of the skin microbiota.Cutibacterium acnes (CECT5684), acne-associated species.Staphylococcus spp were grown in broth / agar Nutrient Broth I medium for 24 h at 37°C. C. acnes was grown in broth / agar Reinforced Clostridial medium for 48-72 h at 37°C in anaerobic conditions, using an anaerobic jar and an anaerobic atmosphere generator. Malasssezia spp were grown in broth / agar OXOID CM0920 medium for at least 96 h at 30°C.

[0156] For MIC determination, the strains were grown as detailed above and diluted to an initial ODgoo of 0.01 in a 96-well plate containing poro-coumaric acid at different concentrations (1, 0.5, 0.1, 0.05, 0.01, 0.005, 0.001 and 0.0005%). After 24 h (Staphylococcus spp), 48 h (Cutibacterium acnes) or 96 h (Malassezia spp), the microbial growth was measured by ODgoo in a spectrophotometer to determinethe minimum concentration necessary to inhibit growth in the liquid culture medium (MIC). To establish the MMC, 10 pl of medium were removed from each well and plated on appropriate agar media; after 24 h (Staphylococcus spp), 48 h (Cutibacterium acnes) or 96 h (Malassezia spp) of incubation, the plates were checked for colonies and the MMC was established as the minimum concentration of product necessary to completely inhibit microbial growth on the agar plates (no visible colonies).Statistical analysis

[0157] For MIC determination, 8 technical replicates were performed. For MMC determination, at least 3 technical replicates were performed. All data were statistically analysed using a Oneway ANOVA test. Statistical significance was set at p < 0.05, 95% of confidence. Graphical results were represented as mean ± SEM (Standard Error of the Mean).Results

[0158] The results of the MIC and MMC assays for para-coumaric acid are summarized below for each microbial strain:• The minimum inhibitory concentration (MIC) of para-coumaric acid in S. aureus CECT239 is 1%, although growth was reduced when the product was used at 0.5% (Figure 30).• The minimum microbicidal concentration (MMC) of para-coumaric acid in S. aureus CECT239 is 1%. (Figure 30)• The minimum inhibitory concentration (MIC) of para-coumaric acid in S. aureus V329 is 1%, although growth was reduced when the product was used at 0.5% and 0.1% (Figure 31)• The minimum microbicidal concentration (MMC) of para-coumaric acid in S. aureus V329 is 1% (Figure 31)• The minimum inhibitory concentration (MIC) of para-coumaric acid in S. epidermidis is 1%, although growth was reduced when the product was used at 0.5% and 0.1% (Figure 32)• The minimum microbicidal concentration (MMC) of para-coumaric acid in S. epidermidis is 1% (Figure 32)• The minimum inhibitory concentration (MIC) of para-coumaric acid in C. acnes is 1%, although growth was reduced when the product was used at 0.5%, 0.1%, 0.05%, 0.01% and 0.005% (Figure 33)• The minimum microbicidal concentration (MMC) of para-coumaric acid in C. acnes is 1% (Figure 33).• The minimum inhibitory concentration (MIC) of para-coumaric acid in M. furfur is 1%,although growth was reduced when the product was used at 0.5% (Figure 34).• The minimum microbicidal concentration (MMC) of poro-coumaric acid in M. furfur is 1% (Figure 34).• The minimum inhibitory concentration (MIC) of poro-coumaric acid in M. restricta is 1%, although growth was reduced when the product was used at 0.5% (Figure 35)• The minimum microbicidal concentration (MMC) of poro-coumaric acid in M. restricta is 1% (Figure 35).Conclusions

[0159] The present example demonstrates that poro-coumaric acid can be applied in concentrations effective toward inhibiting proliferation of microbial organisms relevant to the cosmetic segment. These results demonstrate the utility of poro-coumaric acid and related hydroxycinnamic acids against cosmetic disturbances caused by selected microbial organisms, such as M. furfur, M. restricta, S. aureus, S. epidermidis, and C. acnes, for example acne.Example 5: Effect of zosteric acid and currently used acne and dandruff antimicrobials on human cell viability

[0160] The present example evaluates the toxicity of currently used antimicrobials in acne (benzoyl peroxide and azelaic acid) and dandruff (zinc pyrithione and selenium sulfide) as well as zosteric acid on human cells. In particular, the present example evaluates the concentration at which the different antimicrobials tested inhibit human cell viability.Materials & MethodsAnalytical equipment

[0161] Inverted microscope, laminar flow hood, cell culture incubator (37°C, 5% CO2, 90% relative humidity), Burker chamber, pipettes, statistical analysis software, laminar flow hood for microorganisms, micropipettes, pro-pipette, rack, vortex, orbital shaker with regulated temperature, spectrophotometer and consumables.Reagents

[0162] Distilled water (Braun), cell specific culture medium and supplements (PromoCell), PBS (Gibco), Trypan Blue (Bio-rad), Trypsin (Sigma-Aldrich), Dimethylsulfoxide (DMSO Sigma-Aldrich), MTT reagent [3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide] (Invitrogen), Azelaic acid (Sigma-Aldrich), Benzoyl peroxide with 25% water (Sigma-Aldrich), Selenium sulfide (Sigma-Aldrich), zinc pyrithione (Sigma-Aldrich), zosetric acid (in house production).Procedure

[0163] The cell viability of the human keratinocytes upon treatment with the products was assessed by the MTT viability assay, following the ECVAM Guidelines as established in ECVAM Database Service on Alternative Methods to Animal Experimentation (MTT assay protocol #17). Cells were cultured overnight at a 10,000 cells / well density in a 96 well plate. 24h later, the culture media was replaced with a new culture medium containing the tested sample at 8 different concentrations (0.03%, 0.01%, 0.003%, 0.001%, 0.0003%, 0.0001%, 0.00003% and 0.00001%). After 24 h incubation, the medium was removed, and the MTT solution was added to each well. Plates were incubated at 37°C for 3 h. MTT reactive solution was removed, and 100% DSMO was added to each well to solubilize formazan crystals prior to absorbance measurements at 500 nm and 620 nm as reference on a scanning multiwell spectrophotometer. Data were statistically analysed.Statistical analysis

[0164] For MTT determination, at least 8 technical replicates were performed. All data were statistically analysed using a One-way ANOVO test. Statistical significance was set at p > 0.05% of 95% confidence interval. Graphical results were represented as mean + / - SEM (Standard Error of the Mean).Results

[0165] The cell viability experiment by the MTT assay showed that (Figure 36A-E):Zosteric acid did not decrease cell viability when used at the tested concentrations Azelaic acid did not decrease cell viability when used at the tested concentrations Benzoyl peroxide decreased human cell viability when used at concentrations of 0.003% or aboveSelenium sulfide did not decrease cell viability when used at the tested concentrations Zinc pyrithione decreased human cell viability when used at concentrations of 0.001% or aboveConclusions

[0166] The present example demonstrates that zosteric acid is nontoxic to human keratinocytes at concentrations relevant for topical applications in cosmetics. Similar results were obtained for azelaic acid and selenium sulfide, whereas both benzoyl peroxide and zinc pyrithione were found to strongly reduce human cell viability at concentrations above 0.0003% and 0.0001% respectively. These initial results suggest that zosteric acid is safe to use for topical applications and provide less risk of adverse reactions on the skin.

[0167] While azelaic acid and selenium sulfide did not affect cell viability, both of these ingredientshave substantial disadvantages when compared to zosteric acid. Selenium sulfide is considered toxic to both humans and the environment. In 2021 the US department of health and human services toxicology program identified selenium sulfide as being reasonably anticipated to be a human carcinogen based on sufficient evidence of carcinogenicity from studies in experimental animals. Hence, selenium sulfide was banned from cosmetics at a usage concentration above 1% in both the US, EU and Japan. Azelaic acid is considered safe for both human health and the environment, but due to its relatively low efficacy when applied topically, azelaic acid is used at doses above 10% to be effective for treatment of acne. The high dose combined with a medium cost (Approximately 23 USD / kg) of azelaic acid makes for an expensive price per treatment (0.23 USD / 100 ml of product). This is approximately 10 times as expensive as the expected price for zosteric acid. The price difference is primarily the result of differences in the effective concentrations that can be used when applied topically (Azelaic acid = 10%, Zosteric acid = 1%).Example 6: Comparison of zosteric acid with currently used antimicrobials against C. acnes and M. furfur

[0168] The present example evaluates the overall cost vs. benefits of zosteric acid compared to the most used antimicrobial agents against C. acnes and M. furfur.Materials & MethodsAnalytical equipment

[0169] Microscope, incubator, statistical analysis software, laminar flow hood for microorganisms, micropipettes, pipettes, pro-pipette, rack, vortex, orbital shaker with regulated temperature, spectrophotometer and consumables.Reagents

[0170] Distilled water (Braun), Phosphate buffered saline (Sigma-Aldrich), DMSO (Sigma-Aldrich), Ethanol (Sigma-Aldrich), Oxoid CM0149 medium (Reinforced Clostridial medium), OXOID CM0920 medium, anaerobic jar and anaerobiosis atmosphere generator.Procedure

[0171] The strains used in this study are listed as follows:Malassezia furfur (ATCC 44344), dandruff-associated species.Cutibacterium acnes (CECT5684), acne-associated species.

[0172] C. acnes was grown in RCM OXOID CM0149 medium for 48h at 37°C in an anaerobiosis jar generator. M. furfur was grown in OXOID CM0920 medium for 96h at 32°C. For MIC determination, the strains were grown as detailed above and diluted to an initial ODgoo of 0.04 in a 96-well platecontaining the products at different concentrations (1, 0.5, 0.1, 0.05, 0.01, 0.005, 0.0005%). After 48 / 96 h (for C. Acnes and M. furfur respectively), microbial growth was measured by ODgoo in a spectrophotometer to determine the minimum concentration necessary to inhibit growth in the liquid culture medium (MIC).Statistical analysis

[0173] For MIC determination, 4 technical replicates were performed. All data were statistically analysed using a One-way ANOVO test. Statistical significance was set at p > 0.05% of 95% confidence interval. Graphical results were represented as mean + / - SEM (Standard Error of the Mean).Evaluation of existing ingredientsSelenium sulfide

[0174] Selenium sulfide is a well-known antifungal agent suggested to interfere with the sulphur metabolism in fungal cells thereby killing the fungus. In addition to its antifungal activity, selenium sulfide has also been suggested to be an antimitotic agent, slowing down the growth of epidermal cells which may contribute to its anti-dandruff activity. Selenium sulfide is an efficient antifungal (normal usage concentration in shampoo is approx. 2%) and it has a relatively low price per treatment (-0,04 USD / 100 ml of shampoo). This is cheaper than zosteric acid when produced at small scale but once zosteric acid production is scaled to industrial scale the price per treatment with zosteric acid will be comparable (-0,03 USD / 100 ml of shampoo). While efficient, selenium sulfide is considered toxic to both humans and the environment. In 2021 the US department of health and human services toxicology program identified selenium sulfide as being reasonably anticipated to be a human carcinogen based on sufficient evidence of carcinogenicity from studies in experimental animals. Hence, selenium sulfide was banned from cosmetics at a usage concentration above 1% in both the US, EU and Japan. In addition to being carcinogenic, selenium sulfide is also non-biodegradable and thus accumulates in the environment and is produced from non-renewable resources.Pyrithione zinc

[0175] Pyrithione zinc (or Zinc pyrithione) is a coordination complex of zinc. It has fungistatic activity as it inhibits the division of fungal cells most likely by blocking proton transport and removing the proton motive force. The combination of a relatively low cost (22 USD / kg) and good efficacy results in pyrithione zinc having a low price per treatment (0.02 USD / 100 ml of product) which is 0.01 USD / 100 ml of product cheaper than zosteric acid when produced at industrial scale. However, several recent studies have shown that pyrithione zinc is likely a reprotoxin that can damage the reproductive process. Based on this, the EU prohibited the use of zinc pyrithione in cosmetic products fromDecember 2021. Currently, the use of zinc pyrithione is still allowed in the US, but only at a maximum concentration of 2%. While zinc pyrithione is considered very toxic to aquatic life with long lasting effects, it is biodegradable and zinc pyrithione from cosmetic use does not pose a threat to the environment, but rather to human health.Benzoyl peroxide

[0176] Benzoyl peroxide is an organic peroxide consisting of two benzoyl groups connected by a peroxide. The oxygen-oxygen bond in peroxides is weak, thus benzoyl peroxide readily undergoes homolysis forming two free radicals. These radicals interact nonspecifically with bacterial proteins, interfering with their function, and killing the bacteria resulting in benzoyl peroxide being a potent antibacterial agent targeting C. acnes and other bacteria. Because benzoyl peroxide is an effective antibacterial agent is often used at relatively low doses (2-3%), which combined with its low cost (10 USD / kg) makes for a low cost per treatment (0.02 USD / 100 ml of product). The main disadvantage of benzoyl peroxide is its strong bleaching activity, resulting in it bleaching hair and clothes. Very recently there has also been some concern with regards to benzoyl peroxide degrading to benzene which is a known carcinogen, but this was rebutted by the FDA. Independent of its human toxicity, benzoyl peroxide is considered very damaging to the aquatic environment with long lasting effects although it is biodegradable. Lastly it is produced synthetically and as such from non-renewable resources.Azelaic acid

[0177] Azelaic acid is a saturated dicarboxylic acid. Azelaic acid is a natural weak organic acid that kills bacteria by disabling the bacterium's ability to maintain a pH difference across the bacterial membrane, removing the proton motive force and thus strongly decreasing the efficiency with which the bacteria respire. While efficient in vitro (see example 3) azelaic acid is unfortunately not very efficient when applied topically and must be used at doses above 10% to be effective. The high dose combined with a medium cost (Approximately 23 USD / kg) of azelaic acid makes for an expensive price per treatment (0.23 USD / 100 ml of product). This is approximately 10 times as expensive as the expected price for zosteric acid. The price difference is primarily the results of differences in the effective concentrations that can be used when applied topically (Azelaic acid = 10%, Zosteric acid = 1%).Results

[0178] Results for C. acnes showed that (Figure 37 A-C):The MIC of zosteric acid in C. acnes is 0.5%, although growth was reduced when the product was used at 0.1% and 0.05%.The MIC of benzoyl peroxide in C. acnes is 0.05%, although growth was reduced when theproduct was used at 0.01%.The MIC of azelaic acid in C. acnes is 0.05%, although growth was reduced when the product was used at 0.01% and 0.005%.

[0179] Results for M. furfur showed that (Figure 37 D-F):The MIC of zosteric acid in M. furfur is 1%, although growth was reduced when the product was used at 0.5% and 0.1%.The MIC of zinc pyrithione in M. furfur is 0.01%, although growth was reduced when the product was used at 0.05% and 0.001%. - The MIC of selenium sulfide in M. furfur is 0.01%, although growth was reduced when the product was used at 0.005%.Conclusions

[0180] Zosteric acid presents as a viable alternative to the currently used antimicrobial agents for at least cosmetic application in view of a good activity and a safe toxicology profile.

Claims

Claims1. Cosmetic use of a composition comprising a hydroxycinnamic acid or a derivative thereof for preventing and / or alleviating a topical condition on a subject.

2. The cosmetic use according to claim 1, wherein the topical condition is a skin and / or a scalp condition.

3. The cosmetic use according to claim 1, wherein the skin condition is selected from the group consisting of: acne, rosacea, seborrheic dermatitis, tinea versicolor, and wrinkles.

4. The cosmetic use according to claim 3, wherein the skin condition is acne.

5. The cosmetic use according to claim 2, wherein the scalp condition is selected from the group consisting of: dandruff, dry scalp, oily or greasy scalp, scalp folliculitis, alopecia areata, and scalp acne.

6. The cosmetic use according to claim 2, wherein the scalp condition is dandruff.

7. The cosmetic use according to any one of the preceding claims, wherein the use alleviates and / or prevents one or more of: pimples, blackheads, and cysts.

8. The cosmetic use according to any one of the preceding claims, wherein the use inhibits adherence and / or proliferation of a microbial organism on the skin of the subject without affecting microbial growth of the microbial organism.

9. The cosmetic use according to any one of claims 1 -7, comprising applying the hydroxycinnamic acid or derivative thereof, such as zosteric acid, in a concentration of 0.5% to 1.5%, such as 1.0%, wherein the skin condition is acne.

10. The cosmetic use according to any one of claims 1 -7, comprising applying the hydroxycinnamic acid or derivative thereof, such as zosteric acid, in a concentration of 0.5% to 1.5%, such as 1.0%, wherein the skin condition is dandruff.

11. The cosmetic use according to claim 8, comprising applying the hydroxycinnamic acid or derivativethereof in a concentration of 0.1% or less to the skin, such as 0.009% or less, such as 0.009% or less, such as 0.008% or less, such as 0.007% or less, such as 0.006% or less, such as 0.005% or less, such as 0.004% or less, such as 0.003% or less, such as 0.002% or less, such as 0.001% or less.

12. The cosmetic use according to claim 8, comprising applying the hydroxycinnamic acid or derivative thereof in a concentration of from 0.001% to 0.1% to the skin, such as from 0.001% to 0.005%, such as from 0.005% to 0.01%, such as from 0.01% to 0.02%, such as from 0.02% to 0.03%, such as from 0.03% to 0.04%, such as from 0.04% to 0.05%, such as from 0.05% to 0.06%, such as from 0.06% to 0.07%, such as from 0.07% to 0.08%, such as from 0.08% to 0.09% such as from 0.09% to 0.1%.

13. The cosmetic use according to any one of claims 8-12, wherein the microbial organism is part of a community of microbial organisms comprising a plurality of microbial organisms.

14. The cosmetic use according to any one of claims 8-13, wherein the microbial organism is selected from the group consisting of: M. furfur, M. restricta, or S. aureus, such as S. aureus CECT239 or V329, and S.epidermidis, and C. acnes.

15. The cosmetic use according to claim 14, wherein the microbial organism is M. furfur and the use comprises applying the hydroxycinnamic acid or derivative thereof in a concentration of from 0.001% to 0.1% to the skin, such as from 0.001% to 0.005%, such as from 0.005% to 0.01%, such as from 0.01% to 0.02%, such as from 0.02% to 0.03%, such as from 0.03% to 0.04%, such as from 0.04% to 0.05%, such as from 0.05% to 0.06%, such as from 0.06% to 0.07%, such as from 0.07% to 0.08%, such as from 0.08% to 0.09%, such as from 0.09% to 0.1%.

16. The cosmetic use according to claim 14, wherein the microbial organism is M. restricta and the use comprises applying the hydroxycinnamic acid or derivative thereof in a concentration of from 0.001% to 0.05% to the skin, such as from 0.001% to 0.005%, such as from 0.005% to 0.01%, such as from 0.01% to 0.02%, such as from 0.02% to 0.03%, such as from 0.03% to 0.04%, such as from 0.04% to 0.05%.

17. The cosmetic use according to claim 14, wherein the microbial organism is M. restricta and the use comprises applying the hydroxycinnamic acid or derivative thereof, for example coumaric acid, such as para-coumaric acid, in a concentration of from 0.001% to 0.1% to the skin, such asfrom 0.001% to 0.005%, such as from 0.005% to 0.01%, such as from 0.01% to 0.02%, such as from 0.02% to 0.03%, such as from 0.03% to 0.04%, such as from 0.04% to 0.05%, such as from 0.05% to 0.06%, such as from 0.06% to 0.07%, such as from 0.07% to 0.08%, such as from 0.08% to 0.09%, such as from 0.09% to 0.1%.

18. The cosmetic use according to claim 14, wherein the microbial organism is S. aureus and the use comprises applying the hydroxycinnamic acid or derivative thereof in a concentration of from 0.001% to 0.1% to the skin, such as from 0.001% to 0.005%, such as from 0.005% to 0.01%, such as from 0.01% to 0.02%, such as from 0.02% to 0.03%, such as from 0.03% to 0.04%, such as from 0.04% to 0.05%, such as from 0.05% to 0.06%, such as from 0.06% to 0.07%, such as from 0.07% to 0.08%, such as from 0.08% to 0.09%, such as from 0.09% to 0.1%.

19. The cosmetic use according to claim 14, wherein the microbial organism is C. acnes and the use comprises applying the hydroxycinnamic acid or derivative thereof in a concentration of from 0.001% to 0.01% to the skin, such as from 0.001% to 0.002%, such as from 0.002% to 0.003%, such as from 0.003% to 0.004%, such as from 0.004% to 0.005%, such as from 0.005% to 0.006%, such as from 0.006% to 0.007%, such as from 0.007% to 0.008%, such as from 0.008% to 0.009%, such as from 0.009% to 0.01%.

20. The cosmetic use according to claim 14, wherein the microbial organism is S. epidermidis and the use comprises applying the hydroxycinnamic acid or derivative thereof in a concentration of from 0.001% to 0.05% to the skin, such as from 0.001% to 0.002%, such as from 0.002% to 0.003%, such as from 0.003% to 0.004%, such as from 0.004% to 0.005%, such as from 0.005% to 0.006%, such as from 0.006% to 0.007%, such as from 0.007% to 0.008%, such as from 0.008% to 0.009%, such as from 0.009% to 0.01%, such as from 0.01% to 0.02%, such as from 0.02% to 0.03%, such as from 0.03% to 0.04%, such as from 0.04% to 0.05%.

21. The cosmetic use according to any of the preceding claims, wherein said hydroxycinnamic acid or a derivative thereof is:, or a salt thereof, wherein Ri, R2 and R3 independently are selected from the group consisting of hydrogen (H), hydroxyl (OH), Ci.g-alkyl and Ci.g-alkoxy, -O-SO2-OR5, wherein R5is selected from the group consisting of: hydrogen and Ci.g-alkyl; provided that at least one of Ri, R2 and R3 is hydroxyl (OH) or -O-SO2-OR5, and R4is selected from the group consisting of hydrogen (H) and Ci-g-alkyl.

22. The cosmetic use according to claim 21, wherein R2 is -O-SO2-OR5.

23. The cosmetic use according to claim 21, wherein R2 is -OH.

24. The cosmetic use according to any one of claims 21-22, wherein R2 is -O-SO2-OR5 and R5is hydrogen.

25. The cosmetic use according to any one of claims 21-24, wherein the hydroxycinnamic acid or derivative thereof is zosteric acid.

26. The cosmetic use according to any one of claims 21-24, wherein the hydroxycinnamic acid or derivative thereof is coumaric acid, such as para-coumaric acid.

27. The cosmetic use according to any one of claims 21-26, wherein the hydroxycinnamic acid or a derivative thereof is a salt.

28. The cosmetic use according to any one of claims 21-26, wherein the hydroxycinnamic acid or a derivative thereof is an alkalimetal salt, for example a sodium or a potassium salt, optionally a monosodium or monopotassium salt, or a disodium or dipotassium salt.

29. The cosmetic use according to claim 28, wherein the hydroxycinnamic acid or a derivative thereof is a monosodium or monopotassium salt of zosteric acid.

30. The cosmetic use according to any one of the preceding claims, wherein the composition comprises the hydroxycinnamic acid or derivative thereof in a concentration from about 0.1%w / w to about 10%w / w, water and a preservative.

31. The cosmetic use according to any one of the preceding claims, wherein the composition comprises the hydroxycinnamic acid or derivative thereof with a trans / cis-ratio of at least 90:10, such as at least 91:9, such as at least 92:8, such as at least 93:7, such as at least 94:6, such as at least 95:5, such as at least 96:4, such as at least 97:3, such as at least 98:2, such as at least 99:1, for example 100:0.

32. The cosmetic use according to any one of the preceding claims, wherein the composition is a biobased composition.

33. The cosmetic use according to any one of the preceding claims, wherein the composition comprises at least 20% biobased carbon, such as at least 30% biobased carbon, such as at least 40% biobased carbon, such as at least 50% biobased carbon, such as at least 60% biobased carbon, such as at least 70% biobased carbon, such as at least 75% biobased carbon, such as at least 80% biobased carbon, such as at least 85% biobased carbon, such as at least 90% biobased carbon, such as at least 95% biobased carbon, such as 100% biobased carbon.

34. The cosmetic use according to any one of the preceding claims, wherein the composition comprises from 20% to 100% biobased carbon, such as from 30% to 100% biobased carbon, such as from 40% to 100% biobased carbon, such as from 50% to 100% biobased carbon, such as from 60% to 100% biobased carbon, such as from 70% to 100% biobased carbon, such as from 75% to 100% biobased carbon, such as from 80% to 100% biobased carbon, such as from 85% to 100% biobased carbon, such as from 90% to 100% biobased carbon, such as from 95% to 100% biobased carbon, such as 100% biobased carbon.

35. A composition comprising a hydroxycinnamic acid or derivative thereof according to the formula:, or a salt thereof, wherein Ri, R2 and R3 independently are selected from the group consisting of hydrogen (H), hydroxyl (OH), Ci.g-alkyl and Ci.g-alkoxy, -O-SO2-OR5, wherein R5is selected from the group consisting of: hydrogen and Ci.g-alkyl; provided that at least one of Ri, R2 and R3 is hydroxyl (OH) or -O-SO2-OR5, and R4is selected from the group consisting of hydrogen (H) and Ci-g-alkyl.

36. The composition according to claim 35, wherein R2 is -O-SO2-OR5.

37. The composition according to claim 35, wherein R2 is -OH.

38. The composition according to any one of claims 35-36, wherein R2 is -O-SO2-OR5 and R5is hydrogen.

39. The composition according to any one of claims 35-38, wherein the hydroxycinnamic acid or derivative thereof is zosteric acid.

40. The composition according to any one of claims 35-38, wherein the hydroxycinnamic acid or derivative thereof is coumaric acid, such as para-coumaric acid.

41. The composition according to any one of claims 35-40, wherein the composition comprises the hydroxycinnamic acid or derivative thereof in a concentration from about 0.1%w / w to about 10%w / w, water and a preservative.

42. The composition according to any one of claims 35-41, wherein the composition comprises the hydroxycinnamic acid or derivative thereof with a trans / c / s-ratio of at least 90:10, such as at least 91:9, such as at least 92:8, such as at least 93:7, such as at least 94:6, such as at least 95:5, such as at least 96:4, such as at least 97:3, such as at least 98:2, such as at least 99:1, for example 100:0.

43. The composition according to any one of claims 35-42, wherein the composition is a biobased composition.

44. The composition according to any one of claims 35-43, wherein the composition comprises at least 20% biobased carbon, such as at least 30% biobased carbon, such as at least 40% biobased carbon, such as at least 50% biobased carbon, such as at least 60% biobased carbon, such as at least 70% biobased carbon, such as at least 75% biobased carbon, such as at least 80% biobased carbon, such as at least 85% biobased carbon, such as at least 90% biobased carbon, such as at least 95% biobased carbon, such as 100% biobased carbon.

45. The composition according to any one of claims 35-44, wherein the composition comprises from 20% to 100% biobased carbon, such as from 30% to 100% biobased carbon, such as from 40% to 100% biobased carbon, such as from 50% to 100% biobased carbon, such as from 60% to 100% biobased carbon, such as from 70% to 100% biobased carbon, such as from 75% to 100% biobased carbon, such as from 80% to 100% biobased carbon, such as from 85% to 100% biobased carbon, such as from 90% to 100% biobased carbon, such as from 95% to 100% biobased carbon, such as 100% biobased carbon.

46. A cosmetic product comprising the composition as defined in any one of claims 35-45.

47. The cosmetic product according to claim 46, wherein the cosmetic product is selected from the group consisting of: a shampoo, a conditioner, such as a hair conditioner, a deodorant, a serum, body wash product, a soap, a cream, a lotion, a gel, pads, such as spot pads, and a spray, such as a scalp or skin spray.

48. The cosmetic product according to any one of claims 46-47, wherein the cosmetic product further comprises one or more additional cosmetic agents selected from the group consisting of: benzoyl peroxide, salicylic acid, alpha hydroxy acids, retinoids, ketoconazole, arbutin, kojic acid, vitamin C, and licorice extract.

49. A composition comprising hydroxycinnamic acid or a derivative thereof for use in the treatment of a skin disorder.

50. The composition for use according to claim 49, wherein the skin disorder results from a skin and / ora scalp condition.

51. The composition for use according to any one of claims 49-50, wherein the skin disorder is selected from the group consisting of: acne vulgaris, rosacea, seborrheic dermatitis, tinea versicolor, skin aging, atopic dermatitis, psoriasis, and eczema.

52. The composition for use according to any one of claims 49-51, wherein the skin disorder is acne vulgaris.

53. The composition for use according to any one of claims 51-52, wherein the treatment alleviates and / or reduces one or more of the symptoms selected from the group consisting of: pimples, blackheads, cysts, inflammation, erythema, and scarring.

54. The composition for use according to any one of claims 50, wherein the scalp disorder is selected from the group consisting of: seborrheic dermatitis, scalp psoriasis, folliculitis, alopecia areata, telogen effluvium, and scalp acne.

55. The composition for use according to any one of claims 50, wherein the scalp disorder is seborrheic dermatitis.

56. The composition for use according to any one of claims 50, wherein the scalp disorder is alopecia areata.

57. The composition for use according to claim 50, wherein the skin disorder results from a microbial infection.

58. The composition for use according to claim 57, wherein the microbial infection is caused by one or more microorganisms selected from the group consisting of: M. furfur, M. restricta, S. aureus, C. acnes, and S. epidermidis.

59. The composition for use according to claim 57, wherein the skin disorder is tinea versicolor or seborrheic dermatitis, for example caused by M. furfur.

60. The composition for use according to claim 57, wherein the skin disorder is acne vulgaris orfolliculitis, for example caused by C. acnes.

61. The composition for use according to claim 57, wherein the skin disorder is atopic dermatitis, for example caused by S. epidermidis.

62. The composition for use according to claim 57, wherein the skin disorder is impetigo or folliculitis, for example caused by S. aureus strains CECT239 or V329.

63. The composition for use according to any one of claims 49-57, wherein the microbial organism is M. furfur and the use comprises applying the hydroxycinnamic acid or derivative thereof in a concentration of from 0.5% to 10% to the skin, such as from 0.5% to 1%, such as from 1% to 2%, such as from 2% to 3%, such as from 3% to 4%, such as from 4% to 5%, such as from 5% to 6%, such as from 6% to 7%, such as from 7% to 8%, such as from 8% to 9%, such as from 9% to 10%.

64. The composition for use according to any one of claims 49-57, wherein the microbial organism is M. restricta and the use comprises applying the hydroxycinnamic acid or derivative thereof in a concentration of from 0.1% to 10% to the skin, such as from 0.1% to 1%, such as from 1% to 2%, such as from 2% to 3%, such as from 3% to 4%, such as from 4% to 5%, such as from 5% to 6%, such as from 6% to 7%, such as from 7% to 8%, such as from 8% to 9%, such as from 9% to 10%.

65. The composition for use according to any one of claims 49-57, wherein the microbial organism is S. aureus and the use comprises applying the hydroxycinnamic acid or derivative thereof in a concentration of from 0.5% to 10% to the skin, such as from 0.5% to 1%, such as from 1% to 2%, such as from 2% to 3%, such as from 3% to 4%, such as from 4% to 5%, such as from 5% to 6%, such as from 6% to 7%, such as from 7% to 8%, such as from 8% to 9%, such as from 9% to 10%.

66. The composition for use according to any one of claims 49-57, wherein the microbial organism is C. acnes and the use comprises applying the hydroxycinnamic acid or derivative thereof in a concentration of from 0.05% to 10% to the skin, such as from 0.05% to 1%, such as from 1% to 2%, such as from 2% to 3%, such as from 3% to 4%, such as from 4% to 5%, such as from 5% to 6%, such as from 6% to 7%, such as from 7% to 8%, such as from 8% to 9%, such as from 9% to 10%.

67. The composition for use according to any one of claims 49-57, wherein the microbial organism is S. epidermidis and the use comprises applying the hydroxycinnamic acid or derivative thereof in aconcentration of from 0.05% to 10% to the skin, such as from 0.05% to 1%, such as from 1% to 2%, such as from 2% to 3%, such as from 3% to 4%, such as from 4% to 5%, such as from 5% to 6%, such as from 6% to 7%, such as from 7% to 8%, such as from 8% to 9%, such as from 9% to 10%.

68. The composition for use according to any one of claims 63-66, wherein the hydroxycinnamic acid or derivative thereof is zosteric acid or coumaric acid, for example para-courmaric acid.

69. The composition for use according to claim 68, wherein the hydroxycinnamic acid or derivative thereof is zosteric acid.

70. The composition for use according to any one of claims 49-57, wherein the use comprises applying the hydroxycinnamic acid or derivative thereof in a concentration of from 0.05% to 10% to the skin, such as from 0.05% to 1%, such as from 1% to 2%, such as from 2% to 3%, such as from 3% to 4%, such as from 4% to 5%, such as from 5% to 6%, such as from 6% to 7%, such as from 7% to 8%, such as from 8% to 9%, such as from 9% to 10%.

71. The composition for use according to claim 70, wherein the concentration is from 0.5% to 2%, such as 1%.

72. The composition for use according to any one of claims 49-71, wherein the composition is formulated for topical administration.

73. The composition for use according to any one of claims 49-71, wherein the composition is in the form of a serum, a shampoo, a cream, a lotion, a gel, an ointment, a foam, a spray, a patch, an oil, a balm, a mask, a soap, or a medicated wipe.

74. The composition for use according to any one of claims 49-71, wherein the composition is in the form of a serum or a shampoo.

75. A formulation for topical administration comprising a hydroxycinnamic acid or derivative thereof as defined in any one of claims 21-29, for example zosteric acid, in a concentration of from 0.5% to 1.5%, such as 1%, wherein the formulation is in the form of a serum or a shampoo.

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