Composition for preventing or reducing transepidermal water loss

By applying SCFA components to pregnant or breastfeeding women, the skin barrier function of infants is enhanced, and the problems of infant TEWL-related diseases are solved, achieving reduction of TEWL and enhancement of skin barrier.

CN108472274BActive Publication Date: 2025-08-19SOCIETE DES PRODUITS NESTLE SA
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Patent Information

Application Number
CN201780005466.2
Authority / Receiving Office
CN · China
Patent Type
Patents(China)
Current Assignee / Owner
Priority Date
2016-01-26
Filing Date
2017-01-26
Publication Date
2025-08-19
Estimated Expiration
2037-01-26

AI Technical Summary

Technical Problem

The prior art is difficult to effectively prevent or treat percutaneous moisture loss (TEWL) and related diseases in infants, especially eczema and reactive skin, and weak skin barrier function.

Method used

Pregnant or lactating women are administered short-chain fatty acids (SCFA) components or derivatives thereof, which are passed through the mother to the infant to enhance skin barrier function, reduce TEWL and prevent or treat TEWL-related diseases.

Benefits of technology

Significantly reduces TEWL in infants, prevents or treats eczema and reactive skin, enhances skin barrier function, and improves skin health.

✦ Generated by Eureka AI based on patent content.

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Patent Text Reader

Abstract

The present invention relates to the use of SFCA components, components derived from SCFAs or mixtures thereof to pregnant or lactating women for preventing and / or treating transepidermal water loss (TEWL) and / or TEWL-related diseases and / or enhancing skin barrier function in offspring or breastfed infants.
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Description

Technical Field

[0001] The present invention relates to the use of a short-chain fatty acid (SCFA) component administered to a mother for preventing or treating transepidermal water loss (TEWL) and / or TEWL-related diseases and / or enhancing skin barrier function in offspring or breast-fed infants. Background Art

[0002] The main function of the skin is to protect the body from environmental stress and prevent dehydration.

[0003] TEWL is a dermatological term used to characterize the loss of water from the body's interior through the epidermis (skin) into the surrounding atmosphere via the processes of diffusion and evaporation.

[0004] TWEL is also the most physiologically relevant readout for assessing compromised skin barrier function, as it well determines how a compromised skin barrier ultimately leads to water loss throughout the skin.

[0005] Transepidermal water loss can have genetic and / or environmental etiologies. Specifically, it can be the result of genetic polymorphisms that lead to reduced expression of protective proteins, thereby compromising the skin barrier. Skin inflammation, primarily caused by external stimuli, can also lead to water loss. Both genetic and environmental factors, together or separately, can lead to excessive transepidermal water loss and ultimately trigger different TEWL-related skin diseases, ranging from dry skin to more severe conditions such as eczema.

[0006] Transepidermal water loss with a genetic predisposition can lead to dry or reactive skin or eczema. When this water loss has an environmental component and is associated, for example, with exposure to allergens through the skin, this can lead to allergic eczema / atopic dermatitis, i.e. eczema with allergic sensitization.

[0007] For the development of eczema and reactive skin, a genetic predisposition (genetic polymorphisms, such as the filaggrin gene or SPINK5) and irritants (such as, for example, soap, sweating, stress, cold, wool, allergens) are usually necessary for the disease to develop. Individuals with eczema show skin reactions to factors that normally do not cause any skin irritation in healthy individuals (such as soap, cold, sweating, stress, wool, allergens).

[0008] In TEWL-associated diseases, the normal rate of water loss is increased due to a weakening of the epidermis' barrier function. Consequently, TEWL-associated diseases are primarily characterized by symptoms of dehydrated epidermis, such as dry or scaly skin. In humans, TEWL-associated diseases are often associated with atopic dermatitis (also known as eczema) and / or reactive skin conditions, such as winter rash. Other conditions associated with increased TEWL and inflammatory skin conditions include atopic diathesis in chronological age, injury, infection, and / or severe trauma (e.g., burns), psoriasis, and various inflammatory skin conditions, such as rosacea and perioral dermatitis.

[0009] Measurement of TEWL is therefore a measure of water loss through the epidermis (skin) and is considered one of the best markers of skin barrier function and therefore the risk of developing skin-related diseases.

[0010] Indeed, increased TEWL at 2 days and 2 months of age predicts eczema at 1 year of age (Skin barrier dysfunction measured by transepidermal water loss at 2 days and 2 months predicts and predicts atopic dermatitis at 1 year, Maeve Kelleher et al., JACI, 2014), and enhanced skin barrier function from birth to 6 months significantly reduces (50%) the risk of developing eczema (Emollient enhancement of the skin barrier from birth offers effective atopic dermatitis prevention, Simpson EL. JACI, 2014).

[0011] TEWL measurement can also be used to assess and quantify the clinical outcomes of skin diseases.

[0012] Therefore, the object of the present invention is to provide a composition for maternal administration, which prevents or treats transepidermal water loss and / or TEWL-related diseases in offspring or breastfed infants and / or enhances skin barrier function. Preferably, the composition is administered to pregnant and / or lactating women. Summary of the Invention

[0013] The present invention aims to provide a novel and alternative solution to the problem of preventing or treating transepidermal water loss and / or TEWL-related disorders in infants and / or enhancing skin barrier function. It has surprisingly been found that short-chain fatty acids (SCFAs), when administered to pregnant or lactating women, are useful in preventing or treating transepidermal water loss and / or TEWL-related disorders and / or enhancing skin barrier function and / or preventing eczema in the offspring or infants of the lactating mothers.

[0014] Evaluation of ingredients useful for treating or preventing transepidermal water loss and / or TEWL-related disorders and / or enhancing skin barrier function was evaluated in newborn mice whose mothers received such ingredients during pregnancy.

[0015] The present invention therefore relates to a composition for administration to a mother before and during pregnancy and / or during lactation, comprising SCFAs or ingredients derived from SCFAs, for preventing and / or treating transepidermal water loss and / or TEWL-related diseases and / or enhancing the barrier function of the skin (i.e., the epidermis) of the offspring. The use of the composition results in the prevention and / or treatment of transepidermal water loss in the offspring, enhanced skin barrier protection, in particular the prevention or treatment of TEWL-related diseases, the prevention or treatment of eczema, and / or the prevention or treatment of reactive skin.

[0016] The parent composition can be administered orally, enterally or parenterally.

[0017] The maternal composition can also be a pharmaceutical product. In particular, the composition is suitable for pregnant and lactating mothers.

[0018] In one aspect, the present invention provides a maternal composition as described above for use in therapeutically preventing and / or treating transepidermal water loss (TEWL) and / or TEWL-related diseases and / or for enhancing skin barrier function in the offspring or breastfed infant of a woman to whom the maternal composition is administered.

[0019] In another aspect, the present invention provides non-therapeutic use of the maternal composition according to the present invention for preventing and / or treating transepidermal water loss (TEWL) and / or TEWL-related diseases and / or enhancing skin barrier function in the offspring of a pregnant or lactating woman or a breastfed infant to whom the maternal composition is administered. BRIEF DESCRIPTION OF THE DRAWINGS

[0020] · Figure 1 Shown are transepidermal water losses of 3-day-old mice whose mothers received SCFAs in the drinking water during gestation (results from Example 1).

[0021] · Figure 2Shown are transepidermal water losses of 5-day-old mice whose mothers received a diet containing the fermentable fiber inulin during gestation (results from Example 2).

[0022] · Figure 3 Shown are the results of SFCA measurements in adult mice administered fermentable fiber (results from Example 3).

[0023] definition

[0024] The term "infant" refers to a child under the age of 18 months.

[0025] According to the present invention, the term "offspring infant" or "offspring" refers to a child under 18 months of age whose mother received the maternal composition according to the present invention before pregnancy and / or during pregnancy and / or during breastfeeding.

[0026] The term "breastfed infant" or "breastfed offspring" refers to a child under 18 months of age whose mother received a maternal composition according to the invention before pregnancy and / or during pregnancy and while breastfeeding such infant.

[0027] "Transepidermal water loss (TEWL)" is defined as the amount of water that passes from the body (animal or plant) into the surrounding atmosphere through the epidermal layer (skin) via the processes of diffusion and evaporation. Specifically, symptoms of TEWL are dry or flaky skin.

[0028] "Transepidermal water loss (TEWL) measurements" according to the present invention refer to TEWL measurements in offspring. TEWL measurements are important for assessing the barrier function of the epidermis. The normal TEWL rate is affected by injury, infection, and / or severe damage (e.g., burns). Damage to the stratum corneum and superficial skin layers not only leads to physical fragility but also to excessive water loss. The normal TEWL rate for an adult forearm is 7 ± 3 g·h. -1 ·m -2 The TEWL of newborns is greater due to immature skin. In the sense of the present invention, it is 3 g·h higher than that of the control matched group. -1 ·m -2 A TEWL rate of 1000 s is considered abnormal and is indicative of skin (ie, surface) disease.

[0029] "TEWL-related diseases" are skin conditions in which TEWL is abnormally increased. These conditions include, but are not limited to, dry skin, eczema / atopic dermatitis, reactive skin, burns, psoriasis, dermatitis, rosacea, and primary skin inflammation. The etiology of these conditions is often associated with genetic polymorphisms that result in reduced expression of proteins highly involved in skin barrier function, such as proteins encoded by genes for the epidermal differentiation complex (e.g., filaggrin, involucrin, small proline-rich protein), and proteins involved in tight junctions. Therefore, the present invention relates to the prevention or treatment of eczema or reactive skin, or symptoms caused by reactive skin, burns, psoriasis, dermatitis, rosacea, and primary skin inflammation, dry skin, or scaly skin.

[0030] "Barrier function" or "skin barrier protection" or "skin barrier function" is the function of the (epidermal) barrier to prevent the migration of agents, allergens, microorganisms or water through the epidermal layer.

[0031] The terms "eczema" and "atopic dermatitis" (AD) are used interchangeably in the present invention. Eczema is an inflammatory, chronic, relapsing, non-contagious and pruritic (itch-causing) skin disease. The skin of patients with eczema tends to overreact to irritants, foods and environmental allergens and become red, flaky and very itchy (becoming reactive skin). The skin also becomes susceptible to surface infections caused by bacteria. In human individuals, the skin on the curved surfaces of the joints is often affected. Symptoms may vary from person to person, but usually present in the form of a red, inflamed and itchy rash that can quickly develop into painful raised bumps. The skin tends to be more sensitive and may become thickened, cracked, dry or scaly. Disorders of the epidermal barrier function are considered to explain the pathophysiology of atopic dermatitis. Changes in certain genes encoding structural proteins, epidermal proteases and protease inhibitors predispose to a defective epidermal barrier and increase the risk of developing atopic dermatitis. The close association between both genetic barrier defects and environmental insults and the atopic dermatitis barrier suggests that disorders of epidermal barrier function are a major event in the progression of the disease.

[0032] Topical treatments to enhance barrier function are currently a clinical approach for preventing or treating eczema. A key indicator of barrier function is TEWL. It is hypothesized that administering SCFAs or ingredients that increase SCFA levels in humans to pregnant women can lower TEWL in offspring, thereby treating eczema. Without being bound by theory, it is believed that this effect may be mediated by improving the skin's tight junction system.

[0033] In the context of the present invention, the expression "short-chain fatty acids (also SCFAs)" refers to propionic acid, formic acid, acetic acid, butyric acid, valeric acid, isobutyric acid and isovaleric acid and / or physiologically acceptable salts thereof (such as, for example, calcium, potassium, sodium, magnesium, ammonium salts of propionic acid, formic acid, acetic acid, butyric acid, valeric acid, isobutyric acid and isovaleric acid) or mixtures thereof.

[0034] SCFAs are primarily synthesized through fermentation and are naturally present in some foods, such as milk fat and vinegar. In humans, SCFAs are produced in the intestines from gastrointestinal food; the colon is the primary site of production due to microbial density. SCFAs are metabolites of fermentable substances in the colon and are primarily derived from complex carbohydrates or fermentable fibers such as lactose, prebiotics, and oligosaccharides, but can also be derived from protein fermentation.

[0035] In the context of the present invention, the expression "short-chain fatty acids (also SCFA) ingredients" refers to ingredients that essentially consist of SCFAs as defined above as well as ingredients that naturally contain SCFAs as defined above. Non-limiting examples of this second category of SCFA ingredients are e.g. some dairy products and vinegar.

[0036] In the context of the present invention, the expression "ingredient derived from SCFA" refers to an ingredient that produces SCFAs through mammalian / animal / microbial metabolism in the human / animal body of the individual using the ingredient. Non-limiting examples of ingredients derived from SCFA are:

[0037] Glycerol derivatives, such as mono-, di- and triacylglycerol derivatives into which one or more SCFAs have been incorporated, such as, for example, tributyrin, triacetin, tripropionin;

[0038] Phospholipid derivatives, such as phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine, phosphatidylethanol, in which one or more acyl chains consist of SCFAs;

[0039] Organic esters of SCFAs, such as, for example, methyl, ethyl, propyl or isopropyl esters (non-limiting examples of such organic esters of SFCAs are: ethyl butyrate, ethyl propionate, ethyl acetate, etc.); such esters may be naturally occurring or may be obtained by chemical reactions, for example, by condensation of SCFAs with suitable alcohols (e.g., ethoxylated alcohols);

[0040] Fibers or proteins incorporating SCFAs, such as, for example, butyrated or acetylated fibers,

[0041] For example, butyrated or acetylated starch;

[0042] • Fermentable fibers, such as, for example, fermentable oligosaccharides and starch. Fermentable fibers may include, but are not limited to, pectin, mucilage, gums, galacto-oligosaccharides, oligofructans, inulin, polyfructose, arabinogalactan, hemicellulose, oligosaccharides, or mixtures thereof.

[0043] Ingredients derived from SCFAs can produce SCFAs based on different mechanisms that occur in the human or animal body.

[0044] For example, glycerol and triglyceride derivatives that incorporate SCFAs can generate SCFAs in the human or animal intestine through digestion that occurs in the small intestine.

[0045] For example, fermentable fibers can produce SCFAs in the human or animal intestine, particularly in the colon, by fermentation by microorganisms naturally present therein.

[0046] For example, fiber or starch incorporated with SCFAs can produce or release SCFAs in the human or animal intestine through digestion in the small or large intestine and subsequent fermentation of the non-digested portion of the fiber by microorganisms naturally present in the colon.

[0047] The SFCA ingredients and / or ingredients derived from SCFAs may be incorporated into the parent composition of the present invention as free ingredients, or they may be incorporated into the composition in an encapsulated form, for example to reduce the impact on flavor.

[0048] For the purposes of the present invention, the terms "treat" or "treatment method" refer to alleviating or alleviating symptoms, particularly skin disease symptoms, suffered by a mammal, particularly an animal or a human, and / or assisting in the management of a skin disease. The terms "treatment method" and "treating" also refer to promoting or helping to restore the skin, for example, to improve the appearance and condition of the skin.

[0049] The term "prevent" or "preventing" refers to stopping the appearance of such symptoms suffered by mammals, especially animals or humans or reducing the severity of such symptoms. In addition, the term "prevent" or "preventing" refers to delaying the appearance of symptoms.

[0050] As used herein, the term "enhancing skin barrier function" refers to strengthening the barrier function of the skin. This skin barrier function is assessed by measuring transepidermal water loss in dermatological clinics. "Enhancing skin barrier function" therefore reduces the amount of agents, allergens, microorganisms, or water that migrate through the epidermal layer. Specifically, this enhancement of barrier function can be mediated by reducing the interstitial compartments between the epidermal cell layers. This can be achieved by increasing the number of tight junctions and / or increasing the quality of tight junctions between epidermal cells and / or increasing the protein expression of the epidermal differentiation complex (such as filaggrin, small proline-rich protein, NICE, involucrin, loricrin). As used herein, a "maternal composition" refers to a composition administered to a mammalian mother (specifically, a woman), which can be administered before, during, and / or after pregnancy. The composition is administered to the mother before pregnancy, during pregnancy, or at the beginning of lactation for prevention. Alternatively, administration to the mother can be initiated when a breastfeeding infant develops symptoms requiring treatment. The maternal composition is administered to a mother before pregnancy, during pregnancy, or during lactation to prevent and / or treat transepidermal water loss (TEWL) and / or TEWL-related diseases and / or enhance skin barrier function in the offspring or breast-fed infants of the woman to whom the maternal composition is administered.

[0051] As used herein, the term "pharmaceutical formulation" or "pharmaceutical composition" refers to a composition comprising at least one pharmaceutically active agent, chemical substance, or drug. Pharmaceutical formulations can be in solid or liquid form and can contain at least one additional active agent, carrier, solvent, excipient, or adjuvant as recognized by those skilled in the art. Pharmaceutical formulations can be in the form of tablets, capsules, granules, powders, liquids, or syrups. DETAILED DESCRIPTION

[0052] The headings of the various sections serve to clarify the subject matter and should not be construed as limiting the subject matter. If a range of values is disclosed, it is considered that the range covers every single value, especially every integer. Unless otherwise indicated, values expressed in % refer to weight / weight (w / w) values.

[0053] It has surprisingly been found that SCFAs administered to pregnant or lactating women can be used to reduce transepidermal water loss in the offspring or breastfed infants of the lactating mother and / or prevent or treat TEWL-related disorders and / or enhance skin barrier protection.

[0054] This finding was derived from a mouse model of eczema used to measure TEWL. Therefore, it can be concluded that SFCAs can be used to treat or prevent transepidermal water loss, TEWL-related diseases, eczema, or generally enhance skin barrier function. Without wishing to be bound by any theory, it is believed that SCFAs enhance epidermal barrier function by increasing the number or quality of tight junctions in the epidermal cell layer.

[0055] Matrix composition

[0056] The composition of the present invention comprises at least one SCFA ingredient or one ingredient derived from SCFA as defined above or a mixture thereof.

[0057] The matrix composition may comprise at least one, at least two, at least three or at least four different SCFA ingredients or ingredients derived from SCFAs as defined above.

[0058] The matrix composition may comprise at least one, at least two, at least three, or at least four different SCFA ingredients, ingredients derived from SCFAs, or mixtures thereof.

[0059] The composition may comprise only SCFAs (100%).

[0060] In one embodiment, the SCFA is selected from the group consisting of propionic acid, formic acid, acetic acid, butyric acid, valeric acid, isobutyric acid, and isovaleric acid; physiologically acceptable salts thereof (such as, for example, calcium, potassium, sodium, magnesium, ammonium salts of propionic acid, formic acid, acetic acid, butyric acid, valeric acid, isobutyric acid, and isovaleric acid; and mixtures thereof.

[0061] In another embodiment, the SCFA is selected from the group consisting of propionic acid, acetic acid, butyric acid; physiologically acceptable salts thereof (such as, for example, calcium, potassium, sodium, magnesium, ammonium salts of propionic acid, acetic acid, butyric acid); and mixtures thereof.

[0062] When SCFAs are included in the nutritional composition, the composition may comprise 1% to 100%, 10% to 90%, 20% to 80%, 30% to 70%, 40% to 60% SCFA ingredients and / or ingredients derived from SCFAs.

[0063] In one embodiment, the ingredient derived from SCFAs is selected from:

[0064] Glycerol derivatives, such as mono-, di- and triacylglycerol derivatives into which one or more SCFAs have been incorporated, such as, for example, tributyrin, triacetin, tripropionin;

[0065] Phospholipid derivatives, such as phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine, phosphatidylethanol, in which one or more acyl chains consist of SCFAs;

[0066] Organic esters of SCFAs, such as, for example, methyl, ethyl, propyl or isopropyl esters (non-limiting examples of such organic esters of SFCAs are: ethyl butyrate, ethyl propionate, ethyl acetate, etc.); such esters may be naturally occurring or may be obtained by chemical reactions, for example by condensation of SCFAs with suitable alcohols (e.g., ethoxylated alcohols).

[0067] Fibers or proteins incorporating SCFAs, such as, for example, butyrated or acetylated fibers,

[0068] For example, butyrated or acetylated starch;

[0069] Fermentable fibers, such as, for example, fermentable oligosaccharides and starch. Fermentable fibers may include, but are not limited to, pectin, mucilage, gums, galacto-oligosaccharides, oligofructans, inulin, polyfructose, arabinogalactan, hemicellulose, oligosaccharides, or mixtures thereof;

[0070] Or a mixture of these.

[0071] In one embodiment, the component derived from SCFA is a fermentable fiber. In another embodiment, the component derived from SCFA is a fermentable fiber selected from the group consisting of pectin, mucilage, gum, galacto-oligosaccharide, oligofructose, inulin, polyfructose, arabinogalactan, hemicellulose, oligosaccharide and mixtures thereof.

[0072] preparation

[0073] The parent composition can be formulated into liquid or solid form. The composition can also contain at least one other active agent, carrier, vehicle, excipient or adjuvant, which can be determined by those skilled in the art after reading this disclosure.

[0074] The parent composition may be in the form of a pharmaceutical product. A pharmaceutical product may comprise the composition or kit of the present invention.

[0075] All of the components of the composition may be mixed together, or alternatively the composition may be provided in the form of a kit, wherein the components or groups of components are provided separately and are intended to be consumed together by the woman.

[0076] Preferably, the maternal composition of the present invention is administered to a woman who wishes to become pregnant, for example, during at least 1, 2, 3 or 4 months before pregnancy or the desire to become pregnant. When the composition is administered to a pregnant or lactating woman, the composition is preferably administered for at least 4 weeks, preferably at least 8 weeks, more preferably at least 12 weeks, more preferably at least 16 weeks, more preferably at least 20 weeks, more preferably at least 24 weeks, more preferably at least 28 weeks, even more preferably at least 36 weeks during the gestational or lactation period.

[0077] The maternal composition is administered to a mother before pregnancy, during pregnancy, or during lactation to prevent and / or treat transepidermal water loss (TEWL) and / or TEWL-related diseases and / or enhance skin barrier function in the offspring or breast-fed infants of the woman to whom the maternal composition is administered.

[0078] The maternal composition may be in any form suitable for administering all ingredients to a woman. For example, it may be in the form of a pharmaceutical preparation.

[0079] Reagent test kit

[0080] The above compositions can also be provided as kits. In these kits, all or some of the components of the above compositions are provided in separate (i.e., unmixed) forms. The kits of the present invention may comprise, on the one hand, a SCFA component, a component derived from SCFA, or a mixture thereof, and, on the other hand, any other component in separate form. The kits of the present invention may comprise at least two or three SCFA components, a component derived from SCFA, or a mixture thereof provided in separate form. In an alternative embodiment, the kit may comprise each component of the above compositions in separate form.

[0081] Therapeutic uses and methods

[0082] The maternal composition or kit of the present invention can be used to prevent or treat transepidermal water loss in the offspring of a lactating mother or a breastfed infant, and / or to prevent or treat a TEWL-related disease, and / or to prevent or treat a skin disease characterized by increased TEWL compared to individuals without the disease, and / or to enhance the skin barrier function.

[0083] In one embodiment, the parent composition or kit of the present invention can be used to treat and / or prevent eczema or reactive skin, or to enhance skin barrier function (i.e., epidermal barrier function). The composition or kit can prevent and / or treat an increase in TEWL. The composition or kit can prevent an increase in TEWL such that the individual's TEWL value remains substantially equal to or close to the TEWL of an individual without the disease.

[0084] Normal TEWL measurements in adults (e.g., forearm) and animals (such as rodents) are 7 ± 3 g·h -1 ·m -2 Normal values for infants depend on the infant's age and skin maturity. TEWL measurements are 3 g·h higher than those in the control group. -1 ·m -2 It is defined as an abnormal TEWL measurement result. Therefore, 3 g·h is subtracted from TEWL. -1 ·m -2 Up to 10 g·h -1 ·m -2 A previous TEWL level of (e.g., 10.5, 11, 12, 13, 14, 15, 20, 25) is considered to be associated with TEWL disease treatment. Specifically, a TEWL level greater than 10 g·h -1 ·m -2Subtract 0.5, 1.0, 1.5, 2.0, 3.0, 4.0, 5.0, or 10.0 from the previous TEWL level to more closely approximate 7 ± 3 g·h -1 ·m -2 Values within this range were considered relevant to TEWL treatment.

[0085] The compositions or kits of the present invention may also be used in methods for the therapeutic prevention and / or treatment of skin disorders characterized by an increased TEWL compared to individuals not suffering from the disorder.

[0086] The composition and kit can be provided in a form suitable for oral administration and then administered accordingly. Oral administration is preferred. Administration can be started before pregnancy, during pregnancy or during lactation for prevention. Alternatively, administration can be started to the mother when a breast-feeding infant shows symptoms requiring treatment. Administration is performed daily, 1 to 6 days per week, 2 to 5 days per week, 3 to 4 days per week, and for a duration of at least 1 week to up to 3 years. Administration can be once a day, twice a day, or up to 4 times a day.

[0087] In one embodiment, the composition is intended for ingestion by a human subject (ie, a woman prior to conception or a pregnant or lactating woman).

[0088] In another embodiment, the composition is intended for ingestion by an animal, preferably a cat or dog.

[0089] Non-therapeutic uses and methods

[0090] The maternal composition or kit of the present invention can be used for non-therapeutic prevention or treatment of transepidermal water loss in offspring of lactating mothers and / or breastfed infants, and / or prevention or treatment of TEWL-related diseases, and / or prevention or treatment of skin diseases characterized by increased TEWL compared to individuals without the disease, and / or for enhancing skin barrier function.

[0091] In one embodiment, the parent composition or kit of the present invention can be used for non-therapeutic treatment and / or prevention of eczema or reactive skin, or for enhancing skin barrier function (ie, epidermal barrier function). The composition or kit can prevent and / or treat increased TEWL.

[0092] The compositions or kits of the present invention may also be used in methods for the therapeutic prevention and / or treatment of skin disorders characterized by an increased TEWL compared to individuals not suffering from the disorder.

[0093] The composition and kit can be provided in a form suitable for oral administration and then administered accordingly. Oral administration is preferred. Administration can be started before pregnancy, during pregnancy or during lactation for prevention. Alternatively, administration can be started to the mother when a breast-feeding infant shows symptoms requiring treatment. Administration is performed daily, 1 to 6 days per week, 2 to 5 days per week, 3 to 4 days per week, and for a duration of at least 1 week to up to 3 years. Administration can be once a day, twice a day, or up to 4 times a day.

[0094] In one embodiment, the composition is intended for ingestion by a human subject (ie, a woman prior to conception or a pregnant or lactating woman).

[0095] In another embodiment, the composition is intended for ingestion by an animal, preferably a cat or dog.

[0096] Preparation method

[0097] A method for preparing the above-mentioned composition is provided, and the method comprises providing at least one SCFA ingredient or ingredient derived from SCFA as described above, or a mixture thereof; optionally adding at least one additional ingredient selected from the group consisting of fat, protein, carbohydrate, or a physiologically acceptable excipient; optionally adding at least one nutrient or micronutrient; and adding a carrier and / or water.

[0098] Those skilled in the art will appreciate that they can freely combine all features of the present invention disclosed herein. Specifically, the features described for different embodiments of the present invention can be combined. Other advantages and features of the present invention will be apparent from the accompanying drawings and examples.

[0099] Example

[0100] Example 1: Maternal administration of SCFA reduces transepidermal water loss in offspring

[0101] Breeding pairs were established using 1 Balb / c male mouse and 2 Balb / c female mice.

[0102] On day 1 of pregnancy, female mice received 200 mM sodium acetate or sodium propionate ad libitum in their drinking water. These doses corresponded to 0.05 g / mouse / day to 0.1 g / mouse / day and 0.05 g / mouse / day to 0.08 g / mouse / day, respectively. Control female mice received regular drinking water.

[0103] The cages of the litters were monitored from day 18 to day 24. After the pups were born, the mothers were fed regular drinking water again. Each group in the experiment included 6 to 7 pups.

[0104] Transepidermal water loss (baseline TEWL) was measured using a TEWL meter on day 3 of life, with the unit of measurement being g·h -1 ·m -2 .

[0105] As from Figure 1 The results presented show that administration of SCFAs such as acetate or propionate to pregnant mothers significantly reduced transepidermal water loss in their offspring during the first day after birth.

[0106] Example 2: Administration of fermentable fiber to pregnant mice reduces transepidermal water loss in offspring

[0107] Breeding pairs were established using 1 Balb / c male mouse and 2 Balb / c female mice.

[0108] Female mice were fed a diet enriched with 30% inulin from gestational day 1. Control female mice were fed a diet enriched with 30% cellulose, a non-fermentable fiber.

[0109] The cages of the litters were monitored from day 18 to day 24. After the pups were born, all mothers were re-fed their regular diet containing a 4% fiber mix. Each group in the experiment contained 5 pups.

[0110] Transepidermal water loss (baseline TEWL) was measured using a TEWL meter at 5 days of age, with the unit of measurement being g·h -1 ·m -2 .

[0111] As from Figure 2 The results presented show that administration of inulin reduced transepidermal water loss in the offspring during the first day of life compared to a control diet not containing fermentable fiber.

[0112] Example 3: Administration of fermentable fiber to adult mice increases SCFA .

[0113] Weaned (postnatal day 21) Balb / c mice were fed a diet enriched with 30% fermentable fiber inulin or a control diet containing 30% cellulose for 4 weeks.

[0114] Feces were collected 4 weeks after weaning and the presence of SCFAs was measured by gas-liquid chromatography (GLC; amount of SCFA in μmol / g wet weight). The following SCFAs were measured: acetate, propionate, butyrate, valerate, isobutyrate and isovalerate, and the results are reported in Figure 3 middle.

[0115] The measurement was performed according to the following protocol: SCFAs were separated in acidic solutions (pH 2.0 to 3.0) on a GLC column coated with a polar stationary phase. This allowed for minimal sample preparation (no derivatives) and simple, basic FID detection. SCFAs were extracted from feces using an acidic phosphate buffer containing HgCl2.

[0116] Increased SCFA production was observed in the feces of mice fed inulin compared to mice fed cellulose. Thus, it is also expected that increased SCFA, and more specifically acetate and butyrate, in pregnant women would be associated with reduced TWEL in offspring. Without being bound by theory, this suggests that SCFA or secondary products derived from SCFA may be transferred to the fetus and impart skin physiological properties to the young child, resulting in an enhanced skin barrier function.

Claims

1. Use of a maternal composition comprising an ingredient selected from acetate, propionate and a mixture thereof in the preparation of a medicament for preventing and / or treating transepidermal water loss and / or transepidermal water loss-related diseases in the offspring or breast-fed infants of a woman to whom the maternal composition has been applied and / or for enhancing the skin barrier function.

2. The use according to claim 1, for therapeutically preventing and / or treating transepidermal water loss and / or transepidermal water loss-related diseases in the offspring or breast-fed infants of a woman to whom the maternal composition has been administered and / or for enhancing skin barrier function.

3. The use according to claim 1 or 2, for preventing or treating diseases related to transepidermal water loss.

4. The use according to claim 1 or 2, for preventing or treating atopic dermatitis, dry or reactive skin or skin dehydration.

5. The use according to claim 1 or 2, which is for administration to a mother during pregnancy and / or lactation.

6. The use according to claim 1 or 2, which is for administration to a mother during pregnancy to prevent transepidermal water loss and / or transepidermal water loss-related diseases in offspring and / or to enhance skin barrier function.

7. The use according to claim 1 or 2, wherein the composition is administered orally.

8. The use according to claim 1 or 2, wherein the composition further comprises polyunsaturated fatty acids.

9. The use according to claim 1 or 2, wherein the composition further comprises probiotics.

10. The use according to claim 1 or 2, wherein the composition further comprises polyunsaturated fatty acids and probiotics.

Citation Information

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