Cosmetic methods, uses and cosmetic compositions involving niacinamide

Abstract

A method, preferably a cosmetic and / or non-therapeutic method - of re-balancing a ceramide profile of a ceramide-containing tissue; or - of maintaining a ceramide profile of a ceramide-containing tissue; or - of preventing or treating a disruption of a ceramide profile of a ceramide-containing tissue, wherein the method comprises a step of application of niacinamide to such ceramide-containing tissue.

Description

[0001] NOVEL METHODS, USES AND COSMETIC COMPOSITIONS

[0002] Field of the invention

[0003]

[0001] The invention relates to a method of re-balancing the relative percentage of a ceramide in a ceramide-containing tissue, uses in or for the purpose of re-balancing the relative percentage of a ceramide in a ceramide-containing tissue and compositions for such use.

[0004] Background of the invention

[0005]

[0002] Ceramides play a crucial role in maintaining healthy skin by forming part of the skin's natural barrier, which helps retain moisture and protect against environmental aggressors. Different types of ceramides are necessary because each type serves specific functions in this complex system, contributing to optimal skin hydration, barrier function, and overall skin health. The proportions of each ceramide in the skin vary between individuals living in different environments and individuals of different genetics or skin type. Hence, the specific balance between ceramides on the skin of an individual can be very personal. The specific personal balance between ceramides on the skin of one individual is sometimes also referred to as such individual’s personal ceramide profile.

[0006]

[0003] A disruption in the ceramide profile in one’s skin can lead to reduced softness, resilience and / or hydration of the skin. The skin can become irritated, dry and / or more sensitive. The number of dead skin cells may increase and / or wounds may heal less easily.

[0007]

[0004] There is therefore a desire to maintain the natural ceramide profile in an individual’s skin.

[0008]

[0005] EP0695167B1 describes stimulating the synthesis of ceramides in the epidermis by the topical application of precursors thereof in the biosynthetic pathway and / or by stimulation of the activity of enzymes responsible for catalysing the steps in the biosynthetic pathway that yields ceramide. A disadvantage of such a method is that it is a “one size only” solution. The type of ceramide that is stimulated is dictated by the precursors in the topical application and not by the actual physical needs of the individual to whom the topical application is applied.

[0009]

[0006] Similarly, Tanno et al, in their article titled "Nicotinamide increases biosynthesis of ceramides as well as other stratum corneum lipids to improve the epidermal permeability barrier1', describe an overall increase in ceramide biosynthesis, also reports a “one size only” solution.

[0010]

[0007] There is, however, a growing desire to take into account the needs of the specific individual. The challenge to maintain the natural ceramide profile in an individual’s skin further increases with the desire to apply certain cosmetic ingredients. Many individuals apply cosmetic cleansers on a daily basis to their skin. There are also many individuals who want to prevent or reduce the signs of aging of their skin by applying certain anti-aging ingredients. While traditionally cosmetic compositions including anti-aging ingredients were marketed mostly towards older adults, the trend has nowadays expanded, and now a wide variety of people use anti-aging cosmetics for preventive care and targeted treatment.

[0008] Some of the ingredients in such cleansers and / or anti-aging cosmetics are known to disrupt the personal ceramide balance in an individual’s skin. Prominent examples of such harsh ingredients include alpha hydroxy acid (AHA) and retinol.

[0011]

[0009] To counterbalance the effects of harsh ingredients in a cleanser or anti-aging cosmetic, manufacturers are sometimes adding ceramides to the cleanser or cosmetic composition. However, similar to the composition described in EP0695167B1 , such an addition of ceramide to the cleanser or cosmetic composition comes in a “one size only” and does not take into account the individual needs of the customers’ skin.

[0012]

[0010] Because of these harsh effects of some ingredients such as AHA and retinol, some cosmetic products do not use include them. Unfortunately, however, in this way the customer is missing out on the beneficial effects of the ingredient.

[0013]

[0011] The personal skin ceramide profile can also become disrupted as a consequence of a change in an individual’s hormone balance. For example, Kendall et al, in their article titled “Menopause induces changes to the stratum corneum ceramide profile, which are prevented by hormone replacement therapy”, published in Scientific Reports, December 2022, vol. 12, item 21715, discusses menopause-induced changes to the epidermal ceramide profile. Kendall and all suggest a hormone replacement therapy but such a therapy can be very cumbersome for an individual and may have, currently unexplored, side effects.

[0014]

[0012] It would therefore be an advancement in the art to provide a method of restoring or maintaining an individual’s specific skin ceramide profile during or following a disruption of such ceramide balance caused by the application of a ceramide-disrupting ingredient and / or caused by a change in the individual’s hormone profile.

[0015] Summary of the invention

[0016]

[0013] The inventors have now surprising found that niacinamide can advantageously be used for restoring or maintaining the personal skin ceramide profile during or following a disruption of such ceramide profile, for example caused by the application of a ceramide-disrupting ingredient or a change in the individual’s hormone profile.

[0017]

[0014] Accordingly, in a first aspect, the invention provides a method, preferably a cosmetic and / or non-therapeutic method,

[0018] - of re-balancing a ceramide profile of a ceramide-containing tissue; or

[0019] - of maintaining a ceramide profile of a ceramide-containing tissue; or

[0020] - of preventing or treating a disruption of a ceramide profile of a ceramide-containing tissue, wherein such method comprises the step of application of niacinamide to such ceramide-containing tissue.

[0021] Also is provided a use, preferably a cosmetic and / or non-therapeutic use, of niacinamide

[0022] - in or for the purpose of re-balancing of a ceramide profile of a ceramide-containing tissue;

[0023] - in or for the purpose of maintaining of a ceramide profile of a ceramide-containing tissue or - in or for the purpose of preventing or treating a disruption of a ceramide profile of a ceramide- containing tissue.

[0024]

[0015] The “re-balancing of a ceramide profile of a ceramide-containing tissue” as referred to herein can suitably comprise or consist of the re-balancing of the relative molar percentage, based on the total molar amount of ceramides, of ceramides of at least one ceramide class in a ceramide- containing tissue comprising two or more ceramide classes. Similarly the “maintaining of a ceramide profile of a ceramide-containing tissue” as referred to herein can suitably comprise or consist of the maintaining of the relative molar percentage, based on the total molar amount of ceramides, of ceramides of at least one ceramide class in a ceramide-containing tissue comprising two or more ceramide classes. Similarly the “preventing or treating a disruption of a ceramide profile of a ceramide-containing tissue” as referred to herein can suitably comprise or consist of the preventing or treating a disruption in the relative molar percentage, based on the total molar amount of ceramides, of ceramides of at least one ceramide class in a ceramide-containing tissue comprising two or more ceramide classes.

[0025] Further is provided a cosmetic composition comprising niacinamide, wherein the niacinamide is present as an ceramide-balancing agent.

[0026]

[0016] As explained above, the optimal skin ceramide profile can vary between different individuals due to factors like living environment, genetics and skin type. The skin ceramide profile can be disrupted by different causes.

[0027] Hence, in a second aspect, the invention provides a method, preferably a cosmetic and / or non- therapeutic method,

[0028] - of re-balancing a ceramide profile of a ceramide-containing tissue; or

[0029] - of maintaining a ceramide profile of a ceramide-containing tissue; or

[0030] - of preventing or treating a disruption of a ceramide profile of a ceramide-containing tissue, wherein the method comprises a step of application of a cosmetic composition to such ceramide- containing tissue, wherein the cosmetic composition comprises niacinamide and a ceramide- disrupting ingredient.

[0031] Also is provided a use, preferably a cosmetic and / or non-therapeutic use, wherein the use is a use of niacinamide in a cosmetic composition,

[0032] - in or for the purpose of re-balancing of a ceramide profile of a ceramide-containing tissue;

[0033] - in or for the purpose of maintaining of a ceramide profile of a ceramide-containing tissue; or

[0034] - in or for the purpose of preventing or treating a disruption of a ceramide profile of a ceramide- containing tissue, wherein the cosmetic composition comprises a ceramide-disrupting ingredient and niacinamide. Further is provided a cosmetic composition comprising niacinamide and a ceramide-disrupting ingredient, wherein the niacinamide is present as an ceramide-balancing agent, wherein preferably the niacinamide is present in an amount effective to re-balance the ceramide profile of a ceramide- containing tissue, to maintain a ceramide profile of a ceramide-containing tissue or to prevent or treat a disruption of a ceramide profile of a ceramide-containing tissue.

[0017] Further, in a third aspect, the invention provides a method, preferably a cosmetic and / or non-therapeutic method,

[0035] - of re-balancing a ceramide profile of a ceramide-containing tissue; or

[0036] - of maintaining a ceramide profile of a ceramide-containing tissue; or

[0037] - of preventing or treating a disruption of a ceramide profile of a ceramide-containing tissue, wherein the method comprises a step of applying to such ceramide-containing tissue a cosmetic composition, wherein the cosmetic composition comprises niacinamide; and wherein the ceramide-containing tissue is the ceramide-containing tissue of a menopausal or postmenopausal subject.

[0038] Also is provided a use, preferably a cosmetic and / or non-therapeutic use, wherein the use is a use of niacinamide in a cosmetic composition,

[0039] - in or for the purpose of re-balancing of a ceramide profile of a ceramide-containing tissue of a menopausal subject;

[0040] - in or for the purpose of maintaining of a ceramide profile of a ceramide-containing tissue of a menopausal subject; or

[0041] - in or for the purpose of preventing or treating a disruption of a ceramide profile of a ceramide- containing tissue in a menopausal subject, wherein suitably the cosmetic composition comprises niacinamide.

[0042]

[0018] The methods and uses of the invention can be therapeutic or non-therapeutic. Preferred are the non-therapeutic, cosmetic, methods and uses. However, for certain applications, such as methods and uses associated with the treatment of acne, also therapeutic methods and uses can be preferred.

[0043]

[0019] Advantageously, the above methods and uses allow one to restore or maintain an individual’s specific skin ceramide profile during or following a disruption of such ceramide balance caused by the application of a ceramide-disrupting ingredient and / or caused by a change in the individual’s hormone profile.

[0044] Brief description of the drawings

[0045]

[0001] The invention is illustrated by the following figures:

[0046]

[0002] Figure 1 : Study set-up of the in-vivo study

[0047]

[0003] Figure 2: Corneometer and TEWL results of skin measurements after 4 weeks of treatment, wherein NA =5% Niacinamid formulation. Absolute measured values are shown for Corneometer and TEWL. Corneometer: *** p<0.0001 Anova to PreM placebo day28 and ** p<0.001 to PostM placebo day28 placebo. TEWL: *** p<0.0001 both to placebo of poM and preM groups.

[0048]

[0004] Figure 3: Absolute amounts for each class of ceramide at day28 of the group of postmenopausal individuals treated with niacinamide (“Post B3”, right columns, colored dark grey) and of the group of post-menopausal individuals treated with a placebo (“post”, left columns, colored light grey).

[0005] Figure 4: Percentage (%) change in absolute amounts for each class of ceramide at day28 of the group of post-menopausal individuals treated with niacinamide (group C) and of the group of post-menopausal individuals treated with a placebo (group B). For each class of ceramides the treated group shows an increase in absolute amounts vis-a-vis the placebo group.

[0049]

[0006] Figure 5: Schematic overview of the synthesis of ceramides.

[0050]

[0007] Figure 6: In figure 6 is shown the relative percentage(%) of each class of ceramide, as percentage of the total amount of ceramides present, after 4 weeks (28 days) for the group of premenopausal individuals (“preM”, the most left column indicated for each ceramide, colored light grey), the group of post-menopausal individuals treated with a placebo (“postM” , the middle column, colored middle grey) and the group of post-menopausal individuals treated with niacinamide (“B3”, the most right column indicated for each ceramide, colored dark grey).

[0051]

[0008] Figure 7: Overview of classes of ceramides.

[0052] Detailed description of the invention

[0053] Definitions

[0054]

[0020] Unless defined otherwise or clearly indicated by context, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art.

[0055]

[0021] Throughout the present specification and the accompanying claims, the words "comprise" and "include" and variations such as "comprises", "comprising", "includes" and "including" are to be interpreted inclusively. That is, these words are intended to convey the possible inclusion of other elements or integers not specifically recited, where the context allows.

[0056]

[0022] The articles “a” and “an” are used herein to refer to one or to more than one (i.e. to one or at least one) of the grammatical object of the article. By way of example, “an element” may mean one element or more than one element. When referring to a noun (e.g. a compound, an additive, etc.) in the singular, the plural is meant to be included. Thus, when referring to a specific moiety, e.g. "gene", this means "at least one" of that gene, e.g. "at least one gene", unless specified otherwise.

[0057]

[0023] When referring to a compound of which several isomers exist (e.g. a D and an L enantiomer), the compound in principle includes all enantiomers, diastereomers and cis / trans isomers of that compound that may be used in the particular aspect of the invention; in particular when referring to such as compound, it includes the natural isomer(s).

[0058]

[0024] Unless explicitly indicated otherwise, the various embodiments of the invention described herein can be cross-combined.

[0059]

[0025] The term "cosmetic composition " or “cosmetic preparation” refers in the present document to a composition suitable for cosmetic purposes. Suitably a cosmetic composition is herein understood to be a composition for cosmetic, that is, non-therapeutic use. More preferably the term "cosmetic composition " or “cosmetic preparation” refers in the present document to a composition which is applied to the surface of a mammalian keratinous tissue. The terms "cosmetic composition " or “cosmetic preparation” can comprise or consist of those cosmetic compositions as defined underthe heading "Kosmetika" in Rompp Lexikon Chemie, 10th edition 1997, Georg Thieme Verlag Stuttgart, New York as well as to cosmetic compositions as disclosed in A. Domsch, "Cosmetic Compositions", Verlag fur chemische Industrie (ed. H. Ziolkowsky), 4thedition, 1992. More preferably the "cosmetic composition " or “cosmetic preparation” is a cosmetic preparation, respectively a cosmetic composition, that can be topically applied to mammalian keratinous tissue such as e.g. human skin or hair (including eyelashes, the eyebrows, the nails orthe lips), particularly human skin. Hence, the cosmetic composition is preferably a topical composition.

[0060]

[0026] By a topical composition is herein understood a composition for, preferably external, use on keratinous tissue such as the skin.

[0061]

[0027] The term “keratinous tissue" as used in this document refers to tissue containing keratine, more preferably it means the skin (body, face, contour of the eyes, scalp), head hair, eyelashes, eyebrows, bodily hairs, nails and / or lips. Preferably, the keratinous tissue is the skin and hair.

[0062]

[0028] The phrasings “menopausal subject” “menopausal person” and “menopausal individual” are used interchangeably herein. Similarly, the phrasings “post-menopausal subject” “postmenopausal person” and “ post-menopausal individual” are used interchangeably herein. Further, the phrasings “pre-menopausal subject” “pre-menopausal person” and “pre-menopausal individual” are used interchangeably herein. A pre-menopausal subject is herein understood as having regular menstrual cycles and a post-menopausal subject is herein understood as having had the last menstrual period occurring at least 12 months earlier. By the term “menopausal” reference is made to the transition period between “pre-menopausal” and “post-menopausal”. Such period is herein also referred to as “peri-menopausal”. The phrasings “peri-menopausal subject” “peri-menopausal person” and “peri-menopausal individual” are used interchangeably herein.

[0063] Ceramides

[0064]

[0029] By ceramides are herein preferably understood lipids (fats) that can be present in ceramide-containing tissues such as skin, scalp and hair. Preferably the ceramides in the aspects of the invention are epidermal ceramides. For example, ceramides have a function in the formation of the protective layer of the skin that prevents moisture loss and shields the skin from environmental irritants, pollution, and bacteria.

[0065]

[0030] There exist various types of ceramides. These types of ceramides are herein also referred to as classes of ceramides. The phrasings “ceramide type” and “ceramide class” are used interchangeably herein.

[0066]

[0031] Ceramides can be formed by an amidation reaction between a sphingoid base and a saturated or mono-unsaturated fatty acid. The 12 main ceramide classes are shown in figure 7. However, the diversity of ceramides is very high with subspecies of variable chain length within the main classes.

[0067]

[0032] Preferred ceramides in the aspects of the invention include:

[0068] “ceramide EOS”, also referred to as “ceramide 1 ” or simply “EOS”;

[0069] “ceramide NS”, also referred to as “ceramide 2” or simply “NS”; “ceramide NP”, also referred to as “ceramide 3” or simply “NP”;

[0070] “ceramide EOH”, also referred to as “ceramide 4” or simply “EOH”;

[0071] “ceramide AS”, also referred to as “ceramide 5” or simply “AS”;

[0072] “ceramide AP”, also referred to as “ceramide 6” or simply “AP”;

[0073] “ceramide AH”, also referred to as “ceramide 7” or simply “AH”;

[0074] “ceramide NH”, also referred to as “ceramide 8” or simply “NH”;

[0075] “ceramide EOP”, also referred to as “ceramide 9” or simply “EOP”;

[0076] “ceramide NdS”, also referred to as “ceramide 10” or simply “NdS”;

[0077] “ceramide AdS”, also referred to as “ceramide 11 ” or simply “AdS”; and / or

[0078] “ceramide EOdS”, also referred to as simply “EOdS”.

[0079]

[0033] Preferably the ceramides, respectively the ceramide classes, in all aspects of the invention are human ceramides, respectively human ceramide classes. Preferably the ceramides, respectively the ceramide classes, in all aspects of the invention are epidermal ceramides, respectively epidermal ceramide classes. Most preferably the ceramides, respectively the ceramide classes, in all aspects of the invention are human epidermal ceramides, respectively human epidermal ceramide classes.

[0080]

[0034] An overview of different types of human ceramides is provided by the article of Suzuki et al. titled “Whole picture of human stratum corneum ceramides, including the chain-length diversity of long-chain bases”, published in J. Lipid Res. (2022) vol. 63(7) item 100235, pages 1 to 13, hereby incorporated by reference.

[0081] Ceramide-containinq tissue

[0082]

[0035] The term ceramide-containing tissue as used in this document refers to tissue containing one or more classes of ceramides, more preferably two or more classes ceramides, most preferably three or more classes of ceramides. There is no upper limit in the number of classes of ceramides that can be present. For practical reasons, the number of ceramide classes that can be present in the ceramide-containing tissue may suitably lie in the range from equal to or more than 1 , more preferably from equal to or more than 2, even more preferably from equal to or more than 3, most preferably from equal to or more than 5, to equal to or less than 3000, more suitably equal to or less than 2000, most suitably equal to or less than 1581 .

[0083]

[0036] Preferably the ceramide-containing tissue is a human ceramide-containing tissue, more preferably a human epidermal ceramide-containing tissue. Preferably the ceramide-containing tissue is also a keratinous tissue.

[0084]

[0037] The ceramide-containing tissue preferably comprises or consists of:

[0085] - the skin, more preferably the skin of the body, face, contour of the eyes and / or scalp; and / or

[0086] - the hair, more preferably head hair, eyelashes, eyebrows, bodily hairs.

[0087] More preferably the ceramide-containing tissue comprises or consists of skin, even more preferably the human skin, most preferably the human skin of the face and / or scalp.

[0038] Hence, preferably in the first aspect, the invention provides a method, preferably a cosmetic and / or non-therapeutic method, of re-balancing the relative percentage of a ceramide in a human skin and / or scalp or of maintaining a ceramide profile of a human skin and / or scalp or of preventing or treating a disruption of a ceramide profile of a human skin and / or scalp, such method comprising the application of niacinamide to such human skin and / or scalp. Also is provided a use, preferably a cosmetic and / or non-therapeutic use, of niacinamide in or for the purpose of re-balancing the relative percentage of a ceramide in a human skin and / or scalp, in or for the purpose of maintaining a ceramide profile of a human skin and / or scalp or in or for the purpose of preventing or treating a disruption of a ceramide profile of a human skin and / or scalp. Further is provided a cosmetic composition comprising niacinamide, wherein the niacinamide is present as a ceramide-balancing agent.

[0088]

[0039] Also, preferably in the second aspect, the invention provides a method, preferably a cosmetic and / or non-therapeutic method, of re-balancing the relative percentage of a ceramide in a human skin and / or scalp or of maintaining a ceramide profile of a human skin and / or scalp or of preventing or treating a disruption of a ceramide profile of a human skin and / or scalp, such method comprising the application of a cosmetic composition to such human skin and / or scalp, wherein the cosmetic composition comprises niacinamide and a ceramide-disrupting ingredient. Also is provided a use, preferably a cosmetic and / or non-therapeutic use, of niacinamide in a cosmetic composition, in or for the purpose of re-balancing the relative percentage of a ceramide in a human skin and / or scalp, in or for the purpose of maintaining a ceramide profile of a human skin and / or scalp or in or for the purpose of preventing or treating a disruption of a ceramide profile of a human skin and / or scalp, wherein the cosmetic composition comprises a ceramide-disrupting ingredient and niacinamide. Further is provided a cosmetic composition comprising niacinamide and a ceramide-disrupting ingredient, wherein the niacinamide is present as an ceramide-balancing agent, wherein preferably the niacinamide is present in an amount effective to re-balance the relative percentage of a ceramide in a human skin and / or scalp, to maintain a ceramide profile of a human skin and / or scalp or to prevent or treat a disruption of a ceramide profile of a human skin and / or scalp.

[0089]

[0040] Further, preferably in the third aspect, the invention provides a method, preferably a cosmetic and / or non-therapeutic method, of preventing or treating a disruption in the ceramide profile of a human skin and / or scalp of a menopausal or post-menopausal subject, comprising applying to such human skin and / or scalp a cosmetic composition, wherein the cosmetic composition comprises niacinamide. Also is provided a use, preferably a cosmetic and / or non- therapeutic use, of niacinamide in a cosmetic composition, in or for the purpose of re-balancing the relative percentage of a ceramide in a human skin and / or scalp of a menopausal or postmenopausal subject, in or for the purpose of maintaining a ceramide profile of a human skin and / or scalp of a menopausal or post-menopausal subject or in or for the purpose of preventing or treating a disruption of a ceramide profile of a human skin and / or scalp in a menopausal or post-menopausal subject, wherein the cosmetic composition comprises niacinamide.

[0041] Alternatively, suitably in the first aspect, the invention provides a method, preferably a cosmetic and / or non-therapeutic method, of re-balancing the relative percentage of a ceramide in a hair, preferably human hair, or of maintaining a ceramide profile of a hair, preferably human hair, or of preventing or treating a disruption of a ceramide profile of a hair, preferably human hair,, such method comprising the application of niacinamide to such hair, preferably human hair,. Also is provided a use, preferably a cosmetic and / or non-therapeutic use, of niacinamide in or for the purpose of re-balancing the relative percentage of a ceramide in a hair, preferably human hair,, in or for the purpose of maintaining a ceramide profile of a hair, preferably human hair, or in or for the purpose of preventing or treating a disruption of a ceramide profile of a hair, preferably human hair,. Further is provided a cosmetic composition comprising niacinamide, wherein the niacinamide is present as a ceramide-balancing agent.

[0090]

[0042] Also, suitably in the second aspect, the invention provides a method, preferably a cosmetic and / or non-therapeutic method, of re-balancing the relative percentage of a ceramide in a hair, preferably human hair, or of maintaining a ceramide profile of a hair, preferably human hair, or of preventing or treating a disruption of a ceramide profile of a hair, preferably human hair,, such method comprising the application of a cosmetic composition to such hair, preferably human hair,, wherein the cosmetic composition comprises niacinamide and a ceramide-disrupting ingredient. Also is provided a use, preferably a cosmetic and / or non-therapeutic use, of niacinamide in a cosmetic composition, in or for the purpose of re-balancing the relative percentage of a ceramide in a hair, preferably human hair,, in or for the purpose of maintaining a ceramide profile of a hair, preferably human hair, or in or for the purpose of preventing or treating a disruption of a ceramide profile of a hair, preferably human hair,, wherein the cosmetic composition comprises a ceramide- disrupting ingredient and niacinamide. Further is provided a cosmetic composition comprising niacinamide and a ceramide-disrupting ingredient, wherein the niacinamide is present as an ceramide-balancing agent, wherein preferably the niacinamide is present in an amount effective to re-balance the relative percentage of a ceramide in a hair, preferably human hair,, to maintain a ceramide profile of a hair, preferably human hair, or to prevent or treat a disruption of a ceramide profile of a hair, preferably human hair.

[0091]

[0043] Further, suitably in the third aspect, the invention provides a method, preferably a cosmetic and / or non-therapeutic method, of preventing or treating a disruption in the ceramide profile of a hair, preferably human hair, of a menopausal or post-menopausal subject, comprising applying to such hair, preferably human hair, a cosmetic composition, wherein the cosmetic composition comprises niacinamide. Also is provided a use, preferably a cosmetic and / or non-therapeutic use, of niacinamide in a cosmetic composition, in or for the purpose of re-balancing the relative percentage of a ceramide in a hair, preferably human hair, of a menopausal or post-menopausal subject, in or for the purpose of maintaining a ceramide profile of a hair, preferably human hair, of a menopausal or post-menopausal subject or in or for the purpose of preventing or treating a disruption of a ceramide profile of a hair, preferably human hair, in a menopausal or postmenopausal subject, wherein the cosmetic composition comprises niacinamide.

[0044] More preferably the ceramide-containing tissue is a tissue, more preferably a human tissue, comprising two or more classes, more preferably three or more classes, of ceramide(s) chosen from the group consisting of NDS, NS, NP,NH, NSD, ADS, AS, AP, AH, ASD, ODS, OS, OP, OH, OSD, EODS, EOS, EOP, EOH, EOSD, p-ODS, p-OS, p-OP, p-OH and p-OSD, more preferably chosen from the group consisting of NDS, NS, NP, NH, ADS, AS, AP, AH, EODS, EOS, EOP and EOH.

[0092]

[0045] Preferably the ceramide-containing tissue, more preferably the skin and / or scalp, most preferably the human skin and / or scalp, also comprises collagen. That is, preferably the ceramide- containing tissue is a ceramide-containing tissue comprising at least ceramide and collagen.

[0093]

[0046] Without wishing to be bound by any kind of theory, it is believed that menopausal or postmenopausal individuals may suffer from collagen degradation, resulting into an increase of proline and acetyl-proline in the skin of such post-menopausal individuals. It has been advantageously found that niacinamide counteracts the collagen degradation.

[0094]

[0047] Hence, the invention further provides, in a fourth aspect, a method, preferably a cosmetic and / or non-therapeutic method, of preventing or treating a degradation of collagen in a human skin and / or scalp, such method comprising the application of niacinamide to such human skin and / or scalp. Also is provided a use, preferably a cosmetic and / or non-therapeutic use, of niacinamide in or for the purpose of preventing or treating a degradation of collagen in a human skin and / or scalp.

[0048] More preferably the invention provides a method, preferably a cosmetic and / or non- therapeutic method, of preventing ortreating a degradation of collagen in a human skin and / or scalp of a menopausal or post-menopausal subject, such method comprising the application of niacinamide to such human skin and / or scalp of a menopausal or post-menopausal subject. Also is provided a use, preferably a cosmetic and / or non-therapeutic use, of niacinamide in or for the purpose of preventing or treating a degradation of collagen in a human skin and / or scalp of a menopausal or post-menopausal subject.

[0095]

[0049] Further is provided a cosmetic composition comprising niacinamide, wherein the niacinamide is present as a collagen-protecting agent. Advantageously such a cosmetic composition may also comprise collagen. Such collagen present in the cosmetic composition may be protected by the presence of the niacinamide. That is, advantageously the invention also provides a cosmetic composition comprising niacinamide and collagen, wherein the niacinamide is present as a collagen-protecting agent. More preferably such cosmetic composition comprises niacinamide and collagen and a ceramide-disrupting ingredient, wherein the niacinamide is present as a collagen-protecting agent and as a ceramide-balancing agent. As will be explained below, such a cosmetic composition preferably does not comprise any ceramides itself.

[0096] Ceramide profile

[0097]

[0050] The phrasing “ceramide profile” and “ceramide balance” are used interchangeably herein.

[0051] By a “ceramide profile” or “ceramide balance” is herein preferably understood the specific ratio between two or more classes of ceramides (also referred to as different types of ceramides) present in a ceramide-containing tissue.

[0098]

[0052] More preferably the “ceramide profile” or “ceramide balance” comprises or consists of the ratio between two or more classes of epidermal ceramides in the ceramide-containing tissue. More preferably the “ceramide profile” or “ceramide balance” comprises or consists of the ratio between two or more classes of human ceramides, most preferably two or more classes of human epidermal ceramides in the ceramide-containing tissue. Preferences for the ceramide-containing tissue are as described above.

[0099]

[0053] More preferably a “ceramide profile” or “ceramide balance” is herein understood as the ratio between two or more relative percentages of ceramides of different ceramide classes, wherein each relative percentage is the relative percentage, based on the total amount of ceramides, of ceramides of one ceramide class in a ceramide-containing tissue comprising two or more ceramide classes. Preferably the ceramides and the ceramide classes are human ceramides, respectively human ceramide classes. Preferably the ceramides and the ceramide classes are epidermal ceramides, respectively epidermal ceramide classes.

[0100]

[0054] Still more preferably the “ceramide profile” or “ceramide balance” comprises or consists of the ratio between two or more classes, more preferably three or more classes, even more preferably four or more classes and most preferably five or more classes of ceramide(s) chosen from the group consisting of NDS, NS, NP,NH, NSD, ADS, AS, AP, AH, ASD, ODS, OS, OP, OH, OSD, EODS, EOS, EOP, EOH, EOSD, p-ODS, p-OS, p-OP, p-OH and p-OSD.

[0101]

[0055] Still more preferably the “ceramide profile” or “ceramide balance” comprises or consists of the ratio between two or more classes, more preferably three or more classes, even more preferably four or more classes and most preferably five or more classes of ceramide(s) chosen from the group consisting of AdS, AH, AP, AS, EOdS, EOH, EOP, EOS, NdS, NH, NP and NS.

[0102]

[0056] Most preferably the “ceramide profile” or “ceramide balance” comprises or consists of the ratio between the ceramides of ceramide classes AdS, AH, AP, AS, EOdS, EOH, EOP, EOS, NdS, NH, NP and NS in the ceramide-containing tissue, preferably the human skin and / or scalp.

[0103]

[0057] The ratio can be the weight ratio, volume ratio or molar ratio between the ceramides of the different ceramide classes. More preferably the ratio is a molar ratio. Most preferably the “ceramide profile” or “ceramide balance” comprises or consists of the molar ratio between the ceramides of ceramide classes AdS, AH, AP, AS, EOdS, EOH, EOP, EOS, NdS, NH, NP and NS in the ceramide- containing tissue, preferably the human skin and / or scalp.

[0104]

[0058] Hence, most preferably a “ceramide profile” or “ceramide balance” is herein understood as the molar ratio between two or more relative molar percentages of ceramides of different ceramide classes, wherein each relative molar percentage is the relative molar percentage, based on the total molar amount of ceramides, of ceramides of one ceramide class in a ceramide-containing tissue comprising two or more ceramide classes. Preferably the ceramides and the ceramide classes are human ceramides, respectively human ceramide classes. Preferably the ceramides and the ceramide classes are epidermal ceramides, respectively epidermal ceramide classes.

[0105]

[0059] The ceramide profile in the ceramide-containing tissue of a human individual may differ depending on the living environment, genetics and skin type of the individual. In addition such ceramide profile may be dependent on whether the individual is in a pre-menopausal, menopausal or post-menopausal stage of her life. Most preferably the “ceramide profile” or “ceramide balance” is restored to the (i) the natural “ceramide profile” or “ceramide balance” of the individual prior to suffering from any disruption; and / or (ii) to the “ceramide profile” or “ceramide balance” of the premenopausal stage of life.

[0106]

[0060] In one preferred embodiment the ceramide profile comprises or consists of a molar ratio of the ceramides of the ceramide classes AdS : AH : NdS : NH : NP : NS, most preferably wherein the molar ratio of ceramides of the ceramide classes AdS : AH : NdS : NH : NP : NS is 0.3 : 0.7 : 0.5 : 0.7 : 0.4 : 1 :0.

[0107]

[0061] In another preferred embodiment the ceramide profile comprises or consists of a molar ratio of the ceramides of the ceramide classes AdS : AH : AP : AS : EOdS : EOH : EOP : EOS : NdS : NH : NP : NS, most preferably wherein the molar ratio of ceramides of the ceramide classes AdS : AH : AP : AS : EOdS : EOH : EOP : EOS : NdS : NH : NP : NS is 0.3 : 0.7 : 0.3 : 0.4 : 0.0 : 0.4 : 0.0 : 0.7 : 0.5 : 0.7 : 0.4 : 1 :0.

[0108]

[0062] Advantageously the invention thus provides a method, preferably a cosmetic and / or non- therapeutic method, of maintaining a ceramide profile of a ceramide-containing tissue or of preventing or treating a disruption of a ceramide profile of a ceramide-containing tissue, such method comprising the application of niacinamide to such ceramide-containing tissue, such method comprising the application of a cosmetic composition to such ceramide-containing tissue, wherein the cosmetic composition comprises niacinamide and a ceramide-disrupting ingredient, and wherein the ceramide profile is preferably the ceramide profile prior to a disruption, such as the disruption by a ceramide-disrupting ingredient in the cosmetic composition. Also is provided a use, preferably a cosmetic and / or non-therapeutic use, of niacinamide in a cosmetic composition, in or for the purpose of maintaining a ceramide profile of a ceramide-containing tissue or in or for the purpose of preventing or treating a disruption of a ceramide profile of a ceramide-containing tissue, wherein the cosmetic composition comprises a ceramide-disrupting ingredient and niacinamide, wherein the ceramide profile is preferably the ceramide profile prior to a disruption, such as a disruption by the ceramide-disrupting ingredient in the cosmetic composition. Other preferences are as described herein above and below.

[0109]

[0063] Advantageously the invention also provides a method, preferably a cosmetic and / or non- therapeutic method, of preventing or treating a disruption in the ceramide profile of a ceramide- containing tissue of a subject in a menopausal or post-menopausal stage of life, comprising applying to such ceramide-containing tissue a cosmetic composition, wherein the cosmetic composition comprises niacinamide, and wherein the ceramide profile is preferably the ceramide profile of the ceramide-containing tissue of the subject in the prior pre-menopausal stage of life. Also is provided a use, preferably a cosmetic and / or non-therapeutic use, of niacinamide in a cosmetic composition, in or for the purpose of re-balancing the relative percentage of a ceramide in a ceramide-containing tissue of a menopausal or post-menopausal subject, in or for the purpose of maintaining a ceramide profile of a ceramide-containing tissue of a subject in a menopausal or post-menopausal stage of life or in or for the purpose of preventing or treating a disruption of a ceramide profile of a ceramide-containing tissue in a subject in a menopausal or post-menopausal stage of life, wherein the cosmetic composition comprises niacinamide, and wherein the ceramide profile is preferably the ceramide profile of the ceramide-containing tissue of the subject in the prior pre-menopausal stage of life. Other preferences are as described herein above and below.

[0110]

[0064] In the aspects of the invention, the niacinamide is preferably acting as a ceramide- balancing agent. More preferably the niacinamide is acting as a “ceramide rebalancing agent”. That is, preferably the niacinamide allows one to restore the relative percentage, preferably the relative molar percentage, of ceramides of a ceramide class, as based on the total amount, preferably the total molar amount of ceramides, present in the ceramide-containing tissue, more preferably the human skin and / or scalp. In all aspects of the invention the relative percentages preferably refer to relative molar percentages, based on the total amount of moles of ceramides present, for example the total amount of moles of ceramides present in a ceramide-containing tissue.

[0111]

[0065] As explained above, the action of “re-balancing of a ceramide profile of a ceramide- containing tissue” can therefore be clearly distinguished from the action of “increasing biosynthesis of ceramides” or simply “increasing ceramides”.

[0112]

[0066] Increasing the biosynthesis of ceramides simply leads to a quantitative increase in the total amount of ceramides in a ceramide-containing tissue, this may even mean increasing merely one particular ceramide which is already present in a more than abundant concentration and which is not needed in any higher amount.

[0113]

[0067] In contrast, re-balancing a ceramide profile may advantageously qualitatively modify the relative molar percentages of different ceramide classes within a ceramide-containing tissue. This process does not necessarily increase the total ceramide content but instead may conveniently adjust the ratio between the different types of ceramides in the composition to restore a healthy balance. For example, the re-balancing may lead to increasing, but also (relatively) decreasing the proportion of specific ceramide subclasses.

[0114] Ceramide-disrupting ingredient

[0115]

[0068] By a “ceramide-disrupting ingredient” is herein preferably understood a substance that interferes with the presence of ceramides in a ceramide-containing tissue, for example via the production, structure and / or maintenance of such ceramides in such ceramide-containing tissue.

[0116]

[0069] Preferably the ceramide-disrupting ingredient is chosen from the group consisting of:

[0117] - Strong surfactants, such as sodium lauryl sulfate (SLS);

[0118] - Alcohols, such terpenoid alcohols or such as ethanol; - Exfoliators, such as alpha hydroxy acids (AHAs) or beta hydroxy acids (BHAs), examples including glycolic acid and / or salicylic acid;

[0119] - Isotretinoin (also referred to as “Accutane”):

[0120] - Topical steroids, such as corticosteroids; and combinations of one or more of the these.

[0121]

[0070] The strong surfactants, such as SLS, may strip away natural ceramides along with other lipids from the skin's surface. This can weaken the barrier, leading to dryness and irritation. Alcohols, such as ethanol, can deplete skin lipids, including ceramides, making the skin more vulnerable to dehydration and external irritants. Exfoliators, such as alpha hydroxy acids (AHAs) or beta hydroxy acids (BHAs), including for example glycolic acid or salicylic acid, can compromise the lipid balance in the skin. While exfoliation is important for skin renewal, excessive use of these acids can disrupt ceramides, leading to dryness and irritation. Isotretinoin (Accutane), also known as a medication used to treat severe acne, can reduce lipid production in the skin, including ceramides, resulting in dryness and compromised barrier function. Prolonged use of topical steroids such as corticosteroids can lead to thinning of the skin and disruption of ceramide production, making the skin more susceptible to irritation.

[0122]

[0071] Where the ceramide-disrupting ingredient is isotretinoin, the methods and uses according to the invention may preferably be therapeutic methods and uses.

[0123]

[0072] More preferably the “ceramide-disrupting ingredient” comprises or consists of one or more exfoliators and / or one or more terpenoid alcohols. Most preferably the “ceramide-disrupting ingredient” is an alpha hydroxy acid (AHA), retinol or a combination thereof.

[0124] Niacinamide

[0125]

[0073] Niacinamide [CAS-Nr. 98-92-0] is one of the water-soluble B-complex vitamins which is e.g. available as Niacinamide PC or Niacinamide from Dsm-Firmenich (division DSM Nutritional Products AG, 4303 Kaiseraugst, Switzerland). Niacinamide is also referred to as nicotinamide or pyridine-3-carboxamide and is the amide of niacin (vitamin B3).

[0126]

[0074] Niacinamide is typically well-tolerated by most skin types.

[0127]

[0075] In the methods and uses according to this invention, the niacinamide is preferably applied as part of a cosmetic composition. More preferably the niacinamide is applied to the ceramide- containing tissue, such as preferably the skin, in an amount in the range from equal to or more than 0.2 mg / cm2, still more preferably from equal to or more than 0.5 mg / cm2, and most preferably from equal to or more than 1 .0 mg / cm2, to equal to or less than 20 mg / cm2, more preferably to equal to or less than 10 mg / cm2and most preferably to equal to or less than 5 mg / cm2. Most preferably the niacinamide is applied to the ceramide-containing tissue in an amount of about 2 mg / cm2

[0076] Cosmetic compositions according to this invention preferably comprise niacinamide in an amount in the range from equal to or more than 1 % w / w, more preferably from equal to or more than 2 % w / w, most preferably from equal to or more than 5 % w / w to equal to or less than 20 % w / w, more preferably to equal to or less than 15 % w / w, most preferably to equal to or less than 10 % w / w, based on the total weight of the cosmetic composition. Most preferably the niacinamide is present in cosmetic compositions according to this invention in concentrations ranging from 2% w / wto 10% w / w, based on the total weight of the composition.

[0128] Methods according to the invention

[0129]

[0077] The invention advantageously provides a method, preferably a cosmetic and / or non- therapeutic method,

[0130] - of re-balancing a ceramide profile of a ceramide-containing tissue; or

[0131] - of maintaining a ceramide profile of a ceramide-containing tissue; or

[0132] - of preventing or treating a disruption of a ceramide profile of a ceramide-containing tissue, wherein such method comprises the step of application of a composition comprising niacinamide to such ceramide-containing tissue.

[0133]

[0078] Differently phrased, the invention hence also provides a method, preferably a cosmetic and / or non-therapeutic method, comprising the steps of

[0134] (a) applying of a composition comprising niacinamide to a ceramide-containing tissue, preferably the human skin or scalp; followed by

[0135] (b) re-balancing the ceramide profile of the ceramide-containing tissue; or maintaining the ceramide profile of the ceramide-containing tissue; or preventing or treating a disruption of the ceramide profile of the ceramide-containing tissue.

[0136]

[0079] Preferably the composition above is a cosmetic composition. Preferences for such cosmetic composition are as described herein above and herein below.

[0137]

[0080] Preferably the composition comprises at least niacinamide and a ceramide-disrupting ingredient. In such a case the disruption of the ceramide profile may be a disruption caused by such ceramide-disrupting ingredient. Preferences for the ceramide-disrupting ingredient are as described above. Preferably the composition comprises no or essentially no ceramides.

[0138]

[0081] Preferably the ceramide-containing tissue is the ceramide-containing tissue of a menopausal or post-menopausal subject. More preferably the ceramide-containing tissue is the ceramide-containing tissue of a post-menopausal subject. Such menopausal or post-menopausal subject may suffer from a disrupted ceramide profile and may be in need of treatment thereof.

[0139] Uses according to the invention

[0140]

[0082] The invention advantageously provides a use, preferably a cosmetic and / or non- therapeutic use, of niacinamide

[0141] - in or for the purpose of re-balancing of a ceramide profile of a ceramide-containing tissue;

[0142] - in or for the purpose of maintaining of a ceramide profile of a ceramide-containing tissue or

[0143] - in or for the purpose of preventing or treating a disruption of a ceramide profile of a ceramide- containing tissue, wherein preferably the niacinamide is applied as a composition comprising niacinamide.

[0083] Differently phrased, the invention hence also provides a use, preferably a cosmetic and / or non-therapeutic use, of niacinamide, comprising

[0144] (a) applying of a composition comprising niacinamide to a ceramide-containing tissue, preferably the human skin or scalp; followed by

[0145] (b) re-balancing the ceramide profile of the ceramide-containing tissue; or maintaining the ceramide profile of the ceramide-containing tissue; or preventing or treating a disruption of the ceramide profile of the ceramide-containing tissue.

[0146]

[0084] Preferably the composition above is a cosmetic composition. Preferences for such cosmetic composition are as described herein above and herein below. Preferably the composition comprises no or essentially no ceramides.

[0147]

[0085] Preferably the composition comprises at least niacinamide and a ceramide-disrupting ingredient. Preferences for the ceramide-disrupting ingredient are as described above.

[0148] Preferably the ceramide-containing tissue is the ceramide-containing tissue of a menopausal or post-menopausal subject. More preferably the ceramide-containing tissue is the ceramide- containing tissue of a post-menopausal subject. Such menopausal or post-menopausal subject may suffer from a disrupted ceramide profile and may be in need of treatment thereof.

[0149] Hydration and trans-epidermal water loss

[0150]

[0086] The invention advantageously also provides a method, preferably a cosmetic and / or non- therapeutic method,

[0151] - of re-balancing or restoring the hydration of the skin of a post-menopausal subject; or

[0152] - of maintaining the hydration of the skin of a post-menopausal subject; or

[0153] - of preventing or treating a disruption in the hydration of the skin of a post-menopausal subject; or

[0154] - of re-balancing, restoring, preventing or treating a trans-epidermal water loss of or in the skin of a post-menopausal subject, wherein such method comprises the step of application of a composition comprising niacinamide to such ceramide-containing tissue.

[0155]

[0087] The invention also advantageously provides a use, preferably a cosmetic and / or non- therapeutic use, of niacinamide

[0156] - in or for the purpose of re-balancing or restoring the hydration of the skin of a post-menopausal subject; or

[0157] - in or for the purpose of maintaining the hydration of the skin of a post-menopausal subject; or

[0158] - in or for the purpose of preventing or treating a disruption in the hydration of the skin of a postmenopausal subject; or

[0159] - in or for the purpose of re-balancing, restoring, preventing or treating a trans-epidermal water loss of or in the skin of a post-menopausal subject, wherein preferably the niacinamide is applied as a composition comprising niacinamide.

[0160]

[0088] Preferably the composition above is a cosmetic composition. Preferences for such cosmetic composition are as described herein above and herein below. In the examples, the treatment with niacinamide showed a clear and significant improvement for both hydration and trans-epidermal water loss (TEWL).

[0161] Compositions according to the invention

[0162]

[0089] All compositions, preferably cosmetic compositions, according to the present invention are preferably intended for topical use. Although in some cases a therapeutic application is possible, preferably the cosmetic compositions are non-therapeutic.

[0163]

[0090] The term ‘cosmetic composition’ as used herein refers to compositions, which are used to treat, care for or improve the appearance of the skin and / or the scalp. Particular advantageous cosmetic compositions according to the present invention are skin care preparations.

[0164]

[0091] Preferably the cosmetic compositions according to this invention comprise a cosmetically acceptable carrier. The term ‘cosmetically acceptable carrier’ (also referred to herein as carrier) refers to all vehicles / carriers conventionally used in cosmetic compositions, i.e. which are suitable for topical application to the keratinous tissue, have good aesthetic properties, are compatible with the actives present in the composition, and will not cause any unreasonable safety or toxicity concerns. Such carriers are well-known to one of ordinary skill in the art. The exact amount of carrier will depend upon the actual level of the actives (a) to (c) and any other optional ingredients that one of ordinary skill in the art would classify as distinct from the carrier (e.g., other active ingredients).

[0165]

[0092] In an advantageous embodiment, the cosmetic compositions according to the present invention comprise from about 50% to about 99%, preferably from about 60% to about 98%, more preferably from about 70% to about 98%, such as in particular from about 80% to about 95% of a carrier, based on the total weight of the cosmetic composition. In a particular advantageous embodiment, the carrier consists furthermore of at least 40 wt.-%, more preferably of at least 50 wt.-%, most preferably of at least 55 wt.-% of water, such as in particular of about 55 to about 90 wt.-% of water.

[0166]

[0093] The cosmetic composition can be in the form of a liquid, lotion, cream, foam, scrub, gel, soap bar or toner, or applied with an implement or via a face mask, pad or patch. Non-limiting examples of such compositions include leave-on skin lotions and creams, shampoos, conditioners, shower gels, face wash’s, body wash’s, toilet bars, antiperspirants, deodorants, depilatories, lipsticks, foundations, mascara, sunless tanners and sunscreen lotions.

[0167]

[0094] The cosmetic compositions of the invention (including the carrier) may comprise conventional adjuvants and additives, such as preservatives / antioxidants, fatty substances / oils, organic solvents, silicones, thickeners, softeners, emulsifiers, antifoaming agents, aesthetic components such as fragrances, surfactants, fillers, anionic, cationic, nonionic or amphoteric polymers or mixtures thereof, propellants, acidifying or basifying agents, dyes, colorings / colorants, abrasives, absorbents, chelating agents and / or sequestering agents, essential oils, skin sensates, astringents, pigments or any other ingredients usually formulated into such compositions.

[0095] In accordance with the present invention, the cosmetic compositions according to the invention may also comprise further cosmetically active ingredients conventionally used in cosmetic compositions. Exemplary active ingredients encompass skin lightening agents; UV-filters, agents for the treatment of hyperpigmentation; agents for the prevention or reduction of inflammation; firming, moisturizing, soothing, and / or energizing agents as well as agents to improve elasticity and skin barrier.

[0168]

[0096] Examples of cosmetic excipients, diluents, adjuvants, additives as well as active ingredients commonly used in the skin care industry which are suitable for use in the cosmetic compositions of the present invention are for example described in the International Cosmetic Ingredient Dictionary & Handbook by Personal Care Product Council (http: / / www.personalcarecouncil.org / ), accessible by the online INFO BASE (http: / / online.personalcarecouncil.org / jsp / Home.jsp), without being limited thereto.

[0169]

[0097] The cosmetic composition may or may not comprise ceramides. However, preferably the cosmetic compositions according to the invention comprise, based on the total weight of the cosmetic composition, equal to or less than 10 wt%, more preferably equal to or less than 5 wt%, still more preferably equal to or less than 1 wt%, yet more preferably equal to or less than 0.5 wt%, yet still more preferably equal to or less than 0.1 wt %, even still more preferably equal to or less than 0.05 wt% of ceramides, still more preferably equal to or less than 0.01 wt% of ceramides. Most preferably the cosmetic compositions according to the invention comprise no ceramides. Without wishing to be bound by any kind of theory it is believed that any ceramides in the cosmetic composition could have a disturbing effect on the ceramide profile and may negatively influence the effect of the niacinamide.

[0170]

[0098] Advantageously the cosmetic compositions according to the invention can comprise a ceramide-disrupting ingredient, preferably an alpha hydroxy acid (AHA) or a terpenoid alcohol, preferably retinol. Cosmetic compositions according to this invention preferably comprise retinol in an amount in the range from equal to or more than 0.01 % w / w, more preferably from equal to or more than 0.04 % w / w, most preferably from equal to or more than 0.3 % w / w to equal to or less than 2.0 % w / w, more preferably to equal to or less than 1 .0 % w / w, most preferably to equal to or less than 0.5 % w / w, based on the total weight of the cosmetic composition. Most preferably the retinol is present in an amount of equal to or more than 0.04 to equal to or less than 0.8 wt %, based on the total weight of the composition.

[0171]

[0099] Preferably the composition comprises one or more human milk oligosaccharides as an additional ingredient.

[0172]

[0100] The combination of niacinamide and human milk oligosaccharides (HMO) is novel on its own. The invention therefore also provides a composition comprising:

[0173] - niacinamide, preferably wherein the niacinamide is present as a ceramide-balancing agent; and

[0174] - one or more human milk oligosaccharides.

[0175] The invention further provides a composition comprising:

[0176] - niacinamide, preferably wherein the niacinamide is present as a ceramide-balancing agent; and - a ceramide-disrupting ingredient; and

[0177] - one or more human milk oligosaccharides.

[0178] Preferably such compositions are cosmetic compositions. Preferably such compositions are topical compositions. Further preferences for the niacinamide, the ceramide-disrupting ingredient and the compositions are as described herein above and below. Preferably the one or more human milk oligosaccharides (HMO) are chosen from the group consisting of 2'-fucosyllactose (2'FL), lacto-N- neotetraose (LNnT), 3-fucosyllactose (3FL), difucosyllactose (DFL), Lacto-N-fucopentaose I (LNFP I), 3'Sialyllactose Sodium Salt (3'SL), 6'Sialyllactose Sodium Salt (6'SL), Lacto-N-Tetraose (LNT) and combinations thereof. Most preferably the one or more human milk oligosaccharides (HMO) are Lacto-N-neotetraose (LNnT) or 3-Sialyllactose (3’SL) or a combination thereof.

[0179] In the above compositions the weight ratio between the one or more human milk oligosaccharides and the niacinamide may vary widely. Preferably the weight ratio of the total weight of human milk oligosaccharides to the total weight of niacinamide varies in the range between 1 :100 to 100:1 , more preferably between 1 :10 to 100:1 , most preferably between 1 :5 to 50:1 .

[0180] Also the weight ratio between the one or more human milk oligosaccharides and the ceramide- disrupting ingredient may vary widely. Preferably the weight ratio of the total weight of human milk oligosaccharides to the total weight of ceramide-disrupting ingredient varies in the range between 1 :100 to 100:1 , more preferably between 1 :10 to 100:1 , most preferably between 1 :5 to 50:1 .

[0181]

[0101] As explained by Pagac et al, in their abstract titled “Topical application of human milk oligosaccharides alleviates chronic inflammation of postmenopausal skin”, hormonal changes during menopause can drastically affect the incidence and severity of rosacea, a chronic inflammatory skin condition that causes long-term redness on the face and leads to psychological distress. Pagac et al. state that while prescription medicines help to reduce symptoms, an effective cure for rosacea does not exist and they identify an unmet need to manage such skin disorders associated with menopausal status. Subsequently Pagac et al. elaborate that in a placebo-controlled and split-face clinical trial two biotechnologically produced HMOs, Lacto-N-neotetraose (LNnT) and 3-Sialyllactose (3’SL) were investigated for reduction of rosacea- associated symptoms. (The study cohort consisted of Caucasian (n=63), postmenopausal female volunteers (aged 52-60), diagnosed with mild rosacea (subtype l / ll)). As a result it was found that topical application of either of the two HMO structures significantly reduced inter alia the variations in facial skin redness (after 56 days, 5.1 %, p<0.05, compared to placebo), TEWL (18.6%, p<0.001), sebum (45.9%, p<0.01), skin surface pH (after 7 days, 5.8%, p<0.05) and temperature (1 .2%, p<0.001), increased skin hydration (after 28 days, 12.9%, p<0.05) and microcirculation (after 56 days, 6%, p<0.05), and improved clinician’s erythema assessment (CEA) scores (after 7 days, 13.1 %, p<0.05).

[0182] Pagac et al. concluded that human milk oligosaccharides (HMO) possessed beneficial effects when applied as a novel class of topical skin care active ingredients tailored for postmenopausal women suffering from rosacea-induced inflammatory symptoms. The abstract of Pagac et al. is included herein by reference.

[0102] Thus the invention also provides a cosmetic composition, wherein the cosmetic composition comprises

[0183] - niacinamide in an amount in the range from equal to or more than 1 % w / w, more preferably from equal to or more than 2 % w / w, most preferably from equal to or more than 5 % w / w to equal to or less than 20 % w / w, more preferably to equal to or less than 15 % w / w, most preferably to equal to or less than 10 % w / w, based on the total weight of the cosmetic composition; and

[0184] - retinol in an amount in the range from equal to or more than 0.01 % w / w, more preferably from equal to or more than 0.04 % w / w, most preferably from equal to or more than 0.3 % w / w to equal to or less than 2.0 % w / w, more preferably to equal to or less than 1 .0 % w / w, most preferably to equal to or less than 0.5 % w / w, based on the total weight of the cosmetic composition; and

[0185] - optionally one or more human milk oligosaccharides.

[0186]

[0103] Further the invention also provides a cosmetic composition, wherein the cosmetic composition comprises

[0187] - niacinamide in an amount in the range from equal to or more than 1 % w / w, more preferably from equal to or more than 2 % w / w, most preferably from equal to or more than 5 % w / w to equal to or less than 20 % w / w, more preferably to equal to or less than 15 % w / w, most preferably to equal to or less than 10 % w / w, based on the total weight of the cosmetic composition; and

[0188] - alpha hydroxy acid (AHA) in an amount in the range from equal to or more than 0.01 % w / w, more preferably from equal to or more than 0.04 % w / w, most preferably from equal to or more than 0.3 % w / w to equal to or less than 2.0 % w / w, more preferably to equal to or less than 1 .0 % w / w, most preferably to equal to or less than 0.5 % w / w, based on the total weight of the cosmetic composition; and

[0189] - optionally one or more human milk oligosaccharides.

[0190]

[0104] The cosmetic compositions according to the present invention can be in a wide variety of forms. Non limiting examples include simple solutions (e.g. aqueous, organic solvent, or oil based), emulsion or micro emulsion (in particular of oil-in-water (O / W) or water-in-oil (W / O) type, silicone- in-water (Si / W) or water-in-silicone (W / Si) type, PIT-emulsion, multiple emulsion (e.g. of oil-in- water-in oil (O / W / O) or water-in-oil-in-water (W / O / W) type) or pickering emulsions), as well as solid forms (e.g. hydrogels, alcoholic gels, lipogels, sticks, flowable solids, or amorphous materials).

[0191]

[0105] These product forms may be used for a number of applications, including, but not limited to, gels, creams, ointments, lotions, serums, powder, aerosol sprays or two component dispensing systems.

[0192]

[0106] If the cosmetic composition is an emulsion, such as in particular an O / W-, W / O-, Si / W-, W / Si-, O / W / O-, W / O / W- or a pickering emulsion, then the amount of the oily phase present in such cosmetic emulsions is preferably at least 10 wt.-%, such as in the range of 10 to 60 wt.-%, preferably in the range of 15 to 50 wt.-%, most preferably in the range of 15 to 40 wt.-%, based on the total weight of the composition.

[0193]

[0107] In one embodiment, the cosmetic compositions according to the present invention are advantageously in the form of an oil-in-water (O / W) emulsion comprising an oily phase dispersed in an aqueous phase in the presence of an O / W emulsifier. The preparation of such O / W emulsions is well known to a person skilled in the art.

[0194]

[0108] In another particular advantageous embodiment, the cosmetic compositions according to the present invention are clear serums.

[0109] The cosmetic compositions according to the present invention advantageously comprise a preservative.

[0195]

[0110] The cosmetic compositions according to the invention in general have a pH in the range of 3 to 10, preferably a pH in the range of 4 to 8 and most preferably a pH in the range of 5 to 8. The pH can easily be adjusted as desired with suitable acids, such as e.g. citric acid, or bases, such as sodium hydroxide (e.g. as aqueous solution), triethanolamine (TEA Care), Tromethamine (Trizma Base) and Aminomethyl Propanol (AMP-Ultra PC 2000), according to standard methods in the art.

[0196] Examples

[0197] In-vivo study

[0198]

[0111] The study set-up of the in-vivo study has been illustrated in figure 1 and is described below. Healthy, Caucasian female volunteers, living in a similar environment, aged 48-65, were divided into 3 groups:

[0199] A) One pre-menopausal group including 30 individuals (n = 30); and

[0200] B) One post-menopausal group including 30 individuals (n = 30), which was placebo-treated; and

[0201] C) One post-menopausal group including 30 individuals (n = 30), which was treated with 5% niacinamide (NA).

[0202]

[0112] Pre-menopausal was defined by whether menstrual cycles were regular and postmenopausal by the last menstrual period that occurred at least 12 months ago. Perimenopausal individuals were excluded from this study.

[0203]

[0113] The measured skin parameters included:

[0204] TEWL (as determined by tewameter)

[0205] Hydration (as determined by corneometer)

[0206] The Transepidermal Water Loss (TEWL), is an objective measurement of the amount of water that passively evaporates through skin, i.e. is lost across the stratum corneum.

[0207]

[0114] Via the application of D-Squame tape strips the following was determined: Metabolomics

[0208] Lipidomics

[0209] Microbiome (qPCR method)

[0210] To carry out these tests tape strips 1 to 6 were taken from the cheek of each individual. The tape strips were stored at -80°C whilst waiting for analysis. Protein normalization was carried out by measuring protein content on each tape strip.

[0211] Hydration and TEWL Results

[0212]

[0115] The hydration and TEWL results are illustrated in figure 2.

[0213] Figure 2 includes skin measurements of the premenopausal group (group A, preM) and the postmenopausal groups (groups B and C, respectively poM placebo and poM 5% NA) before dayO (see left columns in figure 2 ) and after treatment day28 (see right columns in figure 2).

[0214] In respect of the hydration results it can be noted that:

[0215] • At T=0 days (“dO” in figure 2) no difference between pre- and post-menopausal group can be seen.

[0216] • After 4 weeks, at T = 28 days (“d28” in figure 2), there is a +23% significant increase visible for the treatment with 5% Niacinamide on the post-menopausal group vs TO and vs placebo. In respect of the TEWL results it can be noted that:

[0217] • At T=0 days (“dO” in figure 2), merely a slight difference (+5%) between pre- and postmenopausal groups is visible.

[0218] • After 4 weeks, at T = 28 days (“d28” in figure 2), there is a -19% significant drop visible for the treatment with 5% Niacinamide on the post-menopausal group vs TO and vs placebo.

[0219]

[0116] The results in figure 2 confirm that the treatment with niacinamide showed a clear and significant improvement for both hydration and TEWL. The baseline TEWL was slightly better in the poM group compared to the PreM. Reduced TEWL in older is group not a complete surprise, as TEWL tends at different body sites to decrease

[0220] Metabolomics results

[0221]

[0117] The metabolic analysis demonstrated that: niacinamide showed decreased isomerization to cis-urocanic acid which is an evidence for biological protection from UV damage in postmenopausal skin niacinamide significantly downregulated imidazole-acetaldehyde and lactic acid as markers for reduced histamine activity

[0222] Without wishing to be bound to any kind of theory, it is believed to be advantageous to use niacinamide for treatment of signs of pH imbalance and / or for upregulating the histidine catabolic pathway in post-menopausal women.

[0223] Lipidomics results

[0224]

[0118] For the lipodomic analysis, tape no 6 was selected.

[0225] It was found that, when determining absolute amounts of each class of ceramide, niacinamide (NA) treatment upregulated ceramides vs placebo with highest increases around 30% for the ceramide types NS, NdS, EOS, AS and EOH. The absolute amounts for each type of ceramide and the differences between postmenopausal group B (treated with placebo) and postmenopausal group C (treated with niacinamide) are illustrated in respectively figure 3 and figure 4.

[0226] The pathway for ceramide synthesis is illustrated in figure 5. Inventors expected niacinamide to support the biosynthetic pathway for ceramides and such was confirmed.

[0227]

[0119] However, surprisingly, not all ceramides were boosted in a similar manner. This became visible when looking at the relative percentages of the ceramides of each class of ceramide. By a relative percentage was herein understood the molar percentage of ceramides of each specific class of ceramides as determined on the basis of the total molar amount of ceramides present.

[0228] The relative molar percentages (molar %) of ceramides of each ceramide class were determined as an average for each group on day 28 (after 4 weeks). The results were shown below in Table 1 and illustrated in figure 6. As shown in Table 1 , when comparing the relative molar percentages of group B (post-menopausal subjects treated with placebo) with the relative molar percentages of group C (post-menopausal subjects treated with niacinamide) it can be seen that for some ceramide classes the relative molar percentage has increased (f), whilst for other ceramide classes the relative molar percentage has decreased ( ). For example, niacinamide treatment rebalanced ceramide levels for NS, NdS, AS and EOS positively and ceramide levels for AP, NP, AdS via relative reductions. That is, the treatment with niacinamide in the post-menopausal individuals is rebalancing the ceramide profile towards the ceramide profile present in the pre-menopausal individuals.

[0229]

[0120] Without wishing to be bound by any kind of theory it is believed that such ceramide profile present in the pre-menopausal individuals is representative for the ceramide profile without and / or before disruptions, also referred to herein as pre-disruption ceramide profile or “natural” or “original” ceramide profile. Hence, the treatment with niacinamide allows one to maintain the “natural” or “original” ceramide profile of a ceramide-containing tissue of an individual and / or allows one to prevent or treat a disruption of a ceramide profile of a ceramide-containing tissue of an individual, even if such individual is undergoing a change in the individual’s hormone balance, for example due to menopause.

[0230]

[0121] To determine the ceramide profile for each group, the found molar percentages for each of AdS, AH, AP, AS, EOdS, EOH, EOP, EOS, NdS, NH, NP, NS were subsequently normalized by dividing each value in the range by the maximum value of that range (here the value for ceramide class NS). The ceramide profiles subsequently found are provided in Table 2 (see below). As illustrated by Table 2, the niacinamide treatment in group C (post-menopausal subjects treated with niacinamide) resulted in a re-balancing of the ceramide profile towards the ceramide profile of group A (pre-menopausal subjects). The ceramide profile of group C and the ceramide profile of group A both reflected a molar ratio of

[0231] AdS : AH : AP : AS : EOdS : EOH : EOP : EOS : NdS : NH : NP : NS =

[0232] 0.3 : 0.7 : 0.3 : 0.4 : 0.0 : 0.4 : 0.0 : 0.7 : 0.5 : 0.7 : 0.4 : 1 :0.

[0233]

[0122] Without wishing to be bound by any kind of theory it is believed that the rebalancing effect of niacinamide (NA) on several ceramides can help for the post-menopausal group to get a similar ceramide profile as the premenopausal group. Hence, the niacinamide treatment restores the natural and highly diverse ceramide profile in the stratum corneum barrier in a selective manner. This is an advantage over external addition of ceramides, which external addition has a low specificity and provides a mere “one size” solution. Table 1 : Relative molar percentages (molar %) of ceramides of each class of ceramide as determined on day 28 (after 4 weeks) and normalized values.

[0234] Table 2: Ceramide profiles of Group A, B and C

Claims

26CLAIMS1 . A method, preferably a cosmetic and / or non-therapeutic method,- of re-balancing a ceramide profile of a ceramide-containing tissue; or- of maintaining a ceramide profile of a ceramide-containing tissue; or- of preventing or treating a disruption of a ceramide profile of a ceramide-containing tissue; or- of re-balancing or maintaining the molar ratio between two or more molar percentages of ceramides of different ceramide classes, in a ceramide-containing tissue comprising such two or more ceramide classes; or- of preventing or treating a disruption of the molar ratio between two or more molar percentages of ceramides of different ceramide classes, in a ceramide-containing tissue comprising such two or more ceramide classes, wherein the method comprises a step of application of niacinamide to such ceramide-containing tissue.

2. The method according to claim 1 , preferably a cosmetic and / or non-therapeutic method,- of re-balancing a ceramide profile of a ceramide-containing tissue; or- of maintaining a ceramide profile of a ceramide-containing tissue; or- of preventing or treating a disruption of a ceramide profile of a ceramide-containing tissue; or- of re-balancing or maintaining the molar ratio between two or more molar percentages of ceramides of different ceramide classes, in a ceramide-containing tissue comprising such two or more ceramide classes; or- of preventing or treating a disruption of the molar ratio between two or more molar percentages of ceramides of different ceramide classes, in a ceramide-containing tissue comprising such two or more ceramide classes, wherein the method comprises a step of application of a cosmetic composition to such ceramide- containing tissue, wherein the cosmetic composition comprises niacinamide and a ceramide- disrupting ingredient.

3. The method according to claim 2, wherein the ceramide-disrupting ingredient is is an alpha hydroxy acid (AHA) or a terpenoid alcohol, preferably retinol.

4. The method according to claim 1 , preferably a cosmetic and / or non-therapeutic method,- of re-balancing a ceramide profile of a ceramide-containing tissue; or- of maintaining a ceramide profile of a ceramide-containing tissue; or- of preventing or treating a disruption of a ceramide profile of a ceramide-containing tissue; or- of re-balancing or maintaining the molar ratio between two or more molar percentages of ceramides of different ceramide classes, in a ceramide-containing tissue comprising such two or more ceramide classes; or- of preventing or treating a disruption of the molar ratio between two or more molar percentages of ceramides of different ceramide classes, in a ceramide-containing tissue comprising such two or more ceramide classes, wherein the method comprises a step of application of niacinamide to such ceramide-containing tissue; and wherein the ceramide-containing tissue is the ceramide-containing tissue of a menopausal or postmenopausal subject.

5. The method according to any one of claims 1 to 4, wherein the ceramide profile comprises or consists of the molar ratio between the ceramides of ceramide classes AdS, AH, AP, AS, EOdS, EOH, EOP, EOS, NdS, NH, NP and NS in the ceramide-containing tissue, preferably the human skin and / or scalp, more preferably wherein such molar ratio is a molar ratio ofAdS : AH : AP : AS : EOdS : EOH : EOP : EOS : NdS : NH : NP : NS = 0.3 : 0.7 : 0.3 : 0.4 : 0.0 : 0.4 : 0.0 : 0.7 : 0.5 : 0.7 : 0.4 : 1 :0.

6. A use, preferably a cosmetic and / or non-therapeutic use, of niacinamide- in or for the purpose of re-balancing of a ceramide profile of a ceramide-containing tissue; or- in or for the purpose of maintaining of a ceramide profile of a ceramide-containing tissue; or- in or for the purpose of preventing or treating a disruption of a ceramide profile of a ceramide- containing tissue; or- in or for the purpose of re-balancing or maintaining the molar ratio between two or more molar percentages of ceramides of different ceramide classes, in a ceramide-containing tissue comprising such two or more ceramide classes; or- in or for the purpose of preventing or treating a disruption of the molar ratio between two or more molar percentages of ceramides of different ceramide classes, in a ceramide-containing tissue comprising such two or more ceramide classes..

7. The use according to claim 6, preferably a cosmetic and / or non-therapeutic use, wherein the use is a use of niacinamide in a cosmetic composition,- in or for the purpose of re-balancing of a ceramide profile of a ceramide-containing tissue; or- in or for the purpose of maintaining of a ceramide profile of a ceramide-containing tissue; or- in or for the purpose of preventing or treating a disruption of a ceramide profile of a ceramide- containing tissue; or- in or for the purpose of re-balancing or maintaining the molar ratio between two or more molar percentages of ceramides of different ceramide classes, in a ceramide-containing tissue comprising such two or more ceramide classes; or- in or for the purpose of preventing or treating a disruption of the molar ratio between two or more molar percentages of ceramides of different ceramide classes, in a ceramide-containing tissue comprising such two or more ceramide classes, wherein the cosmetic composition comprises a ceramide-disrupting ingredient and niacinamide.

8. The use according to claim 7, wherein the ceramide-disrupting ingredient is an alpha hydroxy acid (AHA) or a terpenoid alcohol, preferably retinol.

9. The use according to claim 6, claim 7 or claim 8, preferably a cosmetic and / or non- therapeutic use, wherein the use is a use of niacinamide in a cosmetic composition,- in or for the purpose of re-balancing of a ceramide profile of a ceramide-containing tissue of a menopausal or post-menopausal subject;- in or for the purpose of maintaining of a ceramide profile of a ceramide-containing tissue of a menopausal or post-menopausal subject; or- in or for the purpose of preventing or treating a disruption of a ceramide profile of a ceramide- containing tissue in a menopausal or post-menopausal subject; or- in or for the purpose of re-balancing or maintaining the molar ratio between two or more molar percentages of ceramides of different ceramide classes, in a ceramide-containing tissue, comprising such two or more ceramide classes, in a menopausal or post-menopausal subject; or- in or for the purpose of preventing or treating a disruption of the molar ratio between two or more molar percentages of ceramides of different ceramide classes, in a ceramide-containing tissue, comprising such two or more ceramide classes, in a menopausal or post-menopausal subject, wherein the cosmetic composition comprises niacinamide.

10. The use according to any one of claims 6 to 9, wherein the ceramide profile comprises or consists of the molar ratio between the ceramides of ceramide classes AdS, AH, AP, AS, EOdS, EOH, EOP, EOS, NdS, NH, NP and NS in the ceramide-containing tissue, preferably the human skin and / or scalp, more preferably wherein such molar ratio is a molar ratio ofAdS : AH : AP : AS : EOdS : EOH : EOP : EOS : NdS : NH : NP : NS =0.3 : 0.7 : 0.3 : 0.4 : 0.0 : 0.4 : 0.0 : 0.7 : 0.5 : 0.7 : 0.4 : 1 :0.

11. A cosmetic composition comprising niacinamide, wherein the niacinamide is present as a ceramide-balancing agent.

12. A cosmetic composition, preferably a cosmetic composition according to claim 11 , wherein the cosmetic composition comprises niacinamide and a ceramide-disrupting ingredient, wherein preferably the niacinamide is present in an amount effective- to re-balance a ceramide profile of a ceramide-containing tissue;- to maintain a ceramide profile of a ceramide-containing tissue; or- to prevent or treat a disruption of a ceramide profile of a ceramide-containing tissue.

13. A cosmetic composition according to claim 12, wherein the ceramide-disrupting ingredient is an alpha hydroxy acid (AHA) or a terpenoid alcohol, preferably retinol.

14. A cosmetic composition according to any one of claims 11 to 13, wherein the cosmetic composition comprises no or essentially no ceramides.

15. A cosmetic composition according to any one of claims 11 to 14, wherein the cosmetic composition comprises niacinamide in an amount in the range from equal to or more than 1 % w / w, more preferably from equal to or more than 2 % w / w, most preferably from equal to or more than 5 % w / w to equal to or less than 20 % w / w, more preferably to equal to or less than 15 % w / w, most preferably to equal to or less than 10 % w / w, based on the total weight of the cosmetic composition.

16. A cosmetic composition according to any one of claims 11 to 15, wherein the composition further comprises one or more human milk oligosaccharides.

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