WO2018049557A1 - Méthodes de modification de la composition de la peau - Google Patents

Méthodes de modification de la composition de la peau Download PDF

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Publication number
WO2018049557A1
WO2018049557A1 PCT/CN2016/098820 CN2016098820W WO2018049557A1 WO 2018049557 A1 WO2018049557 A1 WO 2018049557A1 CN 2016098820 W CN2016098820 W CN 2016098820W WO 2018049557 A1 WO2018049557 A1 WO 2018049557A1
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skin
zinc
lipid
staphylococcus
atopic dermatitis
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PCT/CN2016/098820
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English (en)
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Karl Shiqing Wei
He Zhao
Jian Xu
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The Procter & Gamble Company
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Priority to PCT/CN2016/098820 priority Critical patent/WO2018049557A1/fr
Publication of WO2018049557A1 publication Critical patent/WO2018049557A1/fr

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/555—Heterocyclic compounds containing heavy metals, e.g. hemin, hematin, melarsoprol
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
    • A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/19—Cosmetics or similar toiletry preparations characterised by the composition containing inorganic ingredients
    • A61K8/27—Zinc; Compounds thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/33—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing oxygen
    • A61K8/34—Alcohols
    • A61K8/345—Alcohols containing more than one hydroxy group
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/49—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds
    • A61K8/4906—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with one nitrogen as the only hetero atom
    • A61K8/4933—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with one nitrogen as the only hetero atom having sulfur as an exocyclic substituent, e.g. pyridinethione
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0014—Skin, i.e. galenical aspects of topical compositions
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q19/00—Preparations for care of the skin

Definitions

  • the disclosure relates to the fields of cosmetic and therapeutic treatments of mammalian skin.
  • Metal-containing compounds such as metal pyrithiones, including zinc pyrithione, are known to exhibit antimicrobial activity.
  • Zinc pyrithione is used as a bioactive component of shampoos useful in the treatment of dandruff through an anti-fungal effect on skin fungi.
  • surfactants are known to be useful in removing skin microbes and particulate matter (i.e., dirt) from skin and hair in washing formulations, and surfactants in other formulations are known to be used as excipients serving as a wetting agent or stabilizer of particulate compositions, but providing no bioactivity (WO 2014/195872) .
  • Formulations useful in washing skin, treating dandruff, or treating dry skin do not provide compounds or compositions useful in improving the quality and appearance of skin that is healthy or is associated with a skin condition other than dry skin or dandruff. Accordingly, a need continues to exist for materials, e.g., formulations of bioactives, and methods for improving the quality and appearance of skin that is healthy or is associated with a skin condition such as atopic dermatitis (with or without lesions) , skin dysbiosis or acne.
  • the disclosure provides materials and methods for selectively altering the composition of skin microbiota in subjects with amenable skin conditions, i.e., healthy skin or skin with atopic dermatitis (with or without lesions) , skin dysbiosis, and/or acne.
  • the disclosure provides a composition comprising a zinc compound (e.g., a zinc ionophore such as zinc pyrithione) , a biocompatible surfactant (e.g., a mild surfactant such as laureth (n) sulfate (SLEnS) ) , and a lipid.
  • a zinc compound e.g., a zinc ionophore such as zinc pyrithione
  • a biocompatible surfactant e.g., a mild surfactant such as laureth (n) sulfate (SLEnS)
  • a lipid e.g., a mild surfactant such as laureth (n) sulfate (SL
  • compositions according to the disclosure to the skin results in the surprisingly selective inhibition of the Staphylococcus genus including, e.g., S.aureus and S. epidermidis, while enhancing the viability, and thus presence, of other bacterial genera (e.g., Streptococcus, Propionibacterium, Corynebacterium, Micrococcus) .
  • Staphylococcus genus including, e.g., S.aureus and S. epidermidis
  • other bacterial genera e.g., Streptococcus, Propionibacterium, Corynebacterium, Micrococcus
  • the disclosure provides a method of altering the microbiota composition of amenable skin comprising administering an effective amount of a zinc compound, a biocompatible surfactant, and a lipid.
  • Amenable skin is defined herein to include healthy skin and skin with atopic dermatitis (with or without lesions) , skin dysbiosis, or acne, but specifically excluding dry skin, dandruff, the flaky skin associated with dandruff, or the application of bioactives to infundibula, such as hair follicles.
  • Exemplary zinc compounds include a zinc ionophore, such as zinc pyrithione or zinc pyridinethione, or zinc monogylcerolate or a simple zinc salt such as zinc oxide.
  • 0.1-2.0 ⁇ g zinc pyrithione is administered per cm 2 of skin, and the 0.1-2.0 ⁇ g zinc pyrithione per cm 2 of skin may be administered as a body wash for at least four weeks.
  • This aspect includes, e.g., methods in which the zinc is not provided in the form of a zinc-containing layered material, is not provided in association with a polymer or a polymer aggregate, or is not sequestered in micro-or nano-particles.
  • the biocompatible surfactant used in these methods can be, for example, a non-ionic surfactant or an anionic surfactant, such as wherein the anionic surfactant is sodium trideceth (n) sulfate, where n is from 0.5 to 2.7.
  • the lipid composition administered in the methods is, e.g., petrolatum, glyceryl monooleate, glycerin, ceramide, cholesterol, a fatty acid, a triglyceride, a phospholipid, or any combination thereof, e.g., wherein the lipid composition is petrolatum or a mixture of petrolatum and glyceryl monooleate.
  • 20-200 ⁇ g lipid composition can be administered per cm 2 skin.
  • the methods include methods in which the lipid is not silicone oil nor a sphingolipid nor a sphingolipid derivative.
  • This aspect includes methods in which the level of Staphylococcus on the skin is decreased relative to the level of Staphylococcus on the skin prior to administration of the zinc compound, the biocompatible surfactant, and the lipid, such as methods in which the decreased level of Staphylococcus is a decreased level of Staphylococcus aureus or Staphylococcus epidermidis on the skin.
  • the level on the skin of at least one of Streptococcus, Micrococcus, Corynebacterium, or Propionibacterium is selectively increased relative to its level on the skin prior to administration the zinc compound, the biocompatible surfactant, and the lipid.
  • the change in one or more of the above levels may lead to an increase in the Shannon index of about 20%or greater, e.g., at least a 20%increase in the Shannon index.
  • Another aspect of the disclosure provides a method of modulating the relative abundance of at least one skin microbial genus by administering to amenable skin an effective amount of a multi-phase skin improvement composition comprising a cleanser comprising a zinc compound and a lathering biocompatible surfactant, and a benefit agent comprising a lipid.
  • amenable skin is healthy skin or skin with atopic dermatitis (with or without lesions) , skin dysbiosis, and/or acne, but amenable skin specifically excludes dry skin, dandruff, or the flaky skin associated with dandruff.
  • the methods of this aspect of the disclosure specifically exclude the application of bioactives to infundibula, such as hair follicles.
  • the zinc compound can be zinc monoglycerolate, a simple zinc salt (e.g., zinc oxide) , or a zinc ionophore such as zinc pyrithione or zinc pyridinethione.
  • a suitable zinc ionophore is zinc pyrithione or zinc pyridinethione, such as wherein 0.1-2.0 ⁇ g zinc pyrithione is administered per cm 2 of skin.
  • This aspect of the disclosure includes methods wherein the zinc is not provided in the form of a zinc-containing layered material, is not provided in association with a polymer or a polymer aggregate, or is not sequestered in micro-or nano-particles.
  • the biocompatible surfactant used in methods according to this aspect of the disclosure can be a non-ionic surfactant or an anionic surfactant.
  • exemplary anionic surfactants include, e.g., sodium trideceth (n) sulfate, where n is from 0.5 to 2.7.
  • the lipid administered in methods according to this aspect include, for example, petrolatum, glyceryl monooleate, glycerin, ceramide, cholesterol, a fatty acid, a triglyceride, a phospholipid, a glycosphingolipid, or any combination thereof, such as wherein the lipid is petrolatum or a mixture of petrolatum and glyceryl monooleate.
  • 20-200 ⁇ g lipid is administered per cm 2 skin.
  • This aspect includes methods wherein the lipid is not silicone oil nor a sphingolipid nor a sphingolipid derivative. Included in this aspect of the disclosure are methods wherein the relative abundance of skin Staphylococcus is decreased to no more than 25%of the skin microbiota compared to the relative abundance of skin Staphylococcus prior to administration of the cleanser and the benefit agent, and methods wherein, compared to the relative abundance of skin Staphylococcus prior to administration of the cleanser and the benefit agent, the relative abundance of skin Staphylococcus in the skin microbiota is decreased to no more than 12%of the skin microbiota by additional administrations of zinc pyrithione.
  • the methods of this aspect of the disclosure include methods wherein the relative abundance of at least one microbial genus on the skin is increased compared to its relative abundance on the skin prior to administration of the cleanser and the benefit agent, such as wherein the microbial genus is Propionibacterium, Corynebacterium or Streptococcus.
  • a method of altering the microbiota composition of amenable skin comprising administering an effective amount of a zinc compound, a biocompatible surfactant, and a lipid.
  • amenable skin is skin with atopic dermatitis (with or without lesions) , skin dysbiosis, or acne.
  • biocompatible surfactant is a non-ionic surfactant or an anionic surfactant.
  • anionic surfactant is sodium trideceth (n) sulfate, where n is from 0.5 to 2.7.
  • the lipid composition comprises petrolatum, glyceryl monooleate, glycerin, ceramide, cholesterol, a fatty acid, a triglyceride, a phospholipid, or any combination thereof.
  • lipid composition is petrolatum or a mixture of petrolatum and glyceryl monooleate.
  • Staphylococcus is Staphylococcus aureus or Staphylococcus epidermidis.
  • a method of modulating the relative abundance of at least one skin microbial genus by administering to amenable skin an effective amount of a multi-phase skin improvement composition comprising a cleanser comprising a zinc compound and a lathering biocompatible surfactant, and a benefit agent comprising a lipid.
  • amenable skin is skin with atopic dermatitis (with or without lesions) , skin dysbiosis, or acne.
  • biocompatible surfactant is a non-ionic surfactant or an anionic surfactant.
  • anionic surfactant is sodium trideceth (n) sulfate, where n is from 0.5 to 2.7.
  • the lipid comprises petrolatum, glyceryl monooleate, glycerin, ceramide, cholesterol, a fatty acid, a triglyceride, a phospholipid, a glycosphingolipid, or any combination thereof.
  • FIG. 1 Microbiota Diversity. The histograms reveal the identities and relative abundances of 14 bacterial genera and one catch-all category on the skin of healthy subjects, subjects with skin exhibiting atopic dermatitis with lesions, and subject with skin exhibiting atopic dermatitis without lesions (non-lesions) . Staphylococcus is the predominant bacterial genus associated with atopic dermatitis.
  • FIG. 1 Characterization of Skin Microbiota.
  • the graphs in the left panel depict the relative abundance of the Staphylococcus genus in healthy skin, in skin with atopic dermatitis without lesions (non-lesions) , and in skin with atopic dermatitis with lesions.
  • the relative abundances of two Staphylococcal species i.e., S. aureus (left graph) and S. epidermidis (right graph) are presented. It is apparent that Staphylococci, including S. aureus and S. epidermidis, are more abundant in skin with atopic dermatitis, with greatest abundance in skin with atopic dermatitis with lesions.
  • the four graphs show the relative abundances of the following four genera in healthy skin, skin with atopic dermatitis without lesions, and skin with atopic dermatitis with lesions: upper left graph -Streptococcus; upper right graph -Propionibacterium; lower left graph -Micrococcus; and lower right graph -Corynebacterium. Streptococcus and one additional bacterial genus (Kocuria) showed significant differences between healthy skin and skin with atopic dermatitis without lesions when analyzing the unrarefied pipeline.
  • FIG. 3 Diversity in the Skin Microbiota. Samples were taken from 8 locations on the human body of subjects with healthy skin, skin with atopic dermatitis with lesions, and skin with atopic dermatitis without lesions. Samples were subjected to DNA isolation and next generation sequence analysis in conjunction with qPCR to determine the bacterial composition and relative abundances of the skin microbiotas in the 8 locations identified in the figure for each of the three subject types. Results were analyzed and the alpha diversity measure of the Shannon Index showed hat the alpha diversity measure was highest for samples taken from healthy skin, an intermediate alpha diversity measure was found for skin with atopic dermatitis without lesions, and the lowest alpha diversity measure was obtained from skin with atopic dermatitis with lesions. The data show that diversity of the skin microbiota decreases as skin develops atopic dermatitis and the diversity continues to decrease as the atopic dermatitis develops lesions.
  • FIG. 4 Treatment Effects on Skin Microbiota.
  • Subjects with healthy skin, skin with atopic dermatitis without lesions, and skin with atopic dermatitis with lesions were each divided into three treatment groups.
  • Group 1 received a daily 0.5%zinc pyrithione body wash
  • Group 2 received a vehicle (BCP2) body wash
  • Group 3 received a B7U bar soap body wash.
  • BCP2 vehicle
  • BCP2 vehicle
  • B7U bar soap body wash The composition and relative abundances of bacterial genera contributing to the skin microbiota at the onset of the study and after 4 weeks of daily washings are shown for all conditions.
  • “Healthy” is healthy skin;
  • AD. L is atopic dermatitis with lesions at onset of the study, "AD.
  • FIG. 5 Microbiota Shift With Treatment of Atopic Dermatitis Lesions.
  • FIG. 6 Microbiota Shift With Treatment of Atopic Dermatitis Without Lesions.
  • a study mirroring the study described in the brief description of Figure 5 was conducted with subjects having atopic dermatitis without lesions substituted for subjects with atopic dermatitis with lesions.
  • the relative abundance of Staphylococcus was measured using 16S rDNA sequencing and qPCR quantification.
  • Subjects performed the standard leg wash using B7U bar soap, vehicle only (BCP2) , or zinc pyrithione in BCP2 vehicle. Samples were taken at onset of the study to establish a baseline and after four weeks of leg washings.
  • FIG. 7 Skin Microbiota Diversity Following Treatment. Subjects with atopic dermatitis with lesions were analyzed for skin microbiota diversity before and after treatment. The subjects were divided into three experimental groups, with one group washing daily for four weeks with BCP2 vehicle body wash (standard leg wash assay) , a second group washing daily with B7U bar soap and a third group washing daily with zinc pyrithione in BCP2 vehicle. The composition and relative abundances of bacterial genera in the skin microbiota were measured at the onset of the study to obtain a baseline and after four weeks of daily leg washings. The results showed that zinc pyrithione in BCP2 body wash selectively restored the diversity of the skin microbiota to the diversity level seen in healthy controls.
  • BCP2 vehicle body wash standard leg wash assay
  • the disclosure provides materials and methods benefiting man and other animals in improving the quality of healthy skin and skin exhibiting atopic dermatitis (with or without lesions) , skin dysbiosis or acne, i.e., amenable skin conditions.
  • Healthy skin is non-diseased skin, and it is also skin that does not appear to be dry and/or flaky, such as would be found in an individual with dandruff or with clinically dry skin.
  • methods of the disclosure are focused on methods of treating skin and not on methods of treating hair (e.g., methods of delivering a bioactive to a hair follicle or infundibulum) , or dandruff, and do not involve applications to clinically dry skin.
  • compositions and methods of use thereof involve the use of free bioactive compounds, i.e., compounds not bound in polymeric form.
  • the compositions are also not caged in particulate forms.
  • the materials and methods of the disclosure improve the appearance of healthy skin and treat an amenable skin condition of a subject with atopic dermatitis (with or without lesions) , skin dysbiosis and/or acne.
  • a “zinc-containing compound” or a “zinc compound” is any biologically compatible form of zinc resulting in the uptake of biologically active zinc such as simple zinc salts, e.g., zinc oxide and zinc compounds including zinc monoglycerolate and zinc ionophores, such as zinc pyrithione and zinc pyridinethione.
  • biologically active zinc such as simple zinc salts, e.g., zinc oxide and zinc compounds including zinc monoglycerolate and zinc ionophores, such as zinc pyrithione and zinc pyridinethione.
  • the various forms of zinc have been found to have beneficial effects on human skin beyond an anti-microbial action.
  • zinc compositions have been found to improve the quality of healthy skin, e.g., appearance.
  • the zinc according to the disclosure is not in the form of a dried zinc-polymer aggregate.
  • the zinc is not sequestered in particles comprising other compounds such as polymers designed to enhance the anti-microbial properties of certain forms of zinc, such as zinc pyri
  • a “biocompatible surfactant” of the disclosure is any surfactant known in the art to be useful in cleansing skin, including anionic, nonionic, zwitterionic or amphoteric surfactants, provided that the surfactant is also biocompatible, such as mild surfactants like nonionic surfactants but also including sulfate-containing surfactants known to be biocompatible.
  • a biocompatible surfactant is defined as a bioactive compound, and not as an excipient. Consistent with this definition, a biocompatible surfactant refers to any mild surfactant or sulfate-containing surfactant that, in the amounts used in the compositions according to the disclosure, do not harm or otherwise have a deleterious effect on the skin.
  • Biocompatible surfactants include anionic surfactants, including sulfate-containing surfactants, nonionic surfactants, amphoteric surfactants, zwitterionic surfactants, and mixtures thereof.
  • Exemplary surfactants include sodium laureth (n) sulfate (SLEnS) surfactants.
  • the "lipid” according to the disclosure may be any lipid or lipid form known in the art.
  • the lipid may be any of a variety of generally hydrophobic chemical compounds, but a lipid according to the disclosure is not a sphingolipid derivative or a wax.
  • Exemplary lipids include petrolatum, glyceryl monooleate, glycerin, ceramide, cholesterol, a fatty acid, a triglyceride, a phospholipid, or any combination thereof.
  • “Amenable skin condition” means skin having atopic dermatitis without lesions, skin having atopic dermatitis with lesions, skin exhibiting skin dysbiosis, skin exhibiting acne, or healthy skin.
  • An amenable skin condition is expressly defined to exclude skin dryness or skin characterized as exhibiting, or prone to, dandruff, or to skin infundibula, such as hair follicles.
  • Biomarker refers to any biological molecules (genes, proteins, lipids, metabolites) that can, singularly or collectively, reflect the current or predict future state of a biological system.
  • various biomarkers can be indicators of a quality of skin in terms of skin hydration, among several other properties.
  • Non-limiting examples of biomarkers include inflammatory cytokines, natural moisturizing factors, one or more of keratins 1, 10 and 11, lipids and total protein.
  • the response of skin to treatment with compositions, including personal care compositions for example, can be assessed by measuring one or more biomarkers.
  • Multiphase refers to compositions comprising at least two phases which can be chemically distinct (e.g., a cleansing phase and a benefit phase) . Such phases can be in direct physical contact with one another.
  • a personal care composition can be a multiphase personal care composition where phases of the personal care composition can be blended or mixed to a significant degree, but still be physically distinct. In these situations, the physical distinctiveness is undetectable to the naked eye.
  • the personal care composition can be a multiphase personal care composition where the phases are in physical contact and are visually distinct. Visually distinct phases can take many forms, for example, they can appear as striped, marbled, the like.
  • NMF Natural moisturizing factor
  • PCA pyrrolidone carboxylic acid
  • Non-diseased skin refers to skin that is generally free of disease, infection, and/or fungus. As used herein, dry skin is considered to be included in non-diseased skin.
  • “Dry skin” is usually characterized as rough, scaly, and/or flaky skin surface, especially in low humidity conditions and is often associated with the somatosensory sensations of tightness, itch, and/or pain.
  • Package refers to any suitable container for a personal care composition including but not limited to a bottle, tube, jar, non-aerosol pump, and combinations thereof.
  • Personal care composition refers to compositions intended for topical application to the skin.
  • Personal care compositions can be rinse-off formulations, in which the product can be applied topically to the skin or hair and then subsequently rinsed within seconds to minutes from the skin with water. The product could also be wiped off using a substrate. In either case, it is believed at least a portion of the product is left behind (i.e., deposited) on the skin.
  • the personal care compositions can be extrudable or dispensable from a package.
  • the personal care compositions can be in the form of, for example, a liquid, semi-liquid cream, lotion, gel, or a combination thereof. Examples of personal care compositions can include but are not limited to body wash, moisturizing body wash, shower gels, skin cleansers, cleansing milks, in shower body moisturizer, and cleansing compositions used in conjunction with a disposable cleansing cloth.
  • “Shannon Index” is given the meaning it has acquired in the art of a measure of biodiversity.
  • STnS refers to sodium trideceth (n) sulfate, wherein n can define the average number of moles of ethoxylate per molecule.
  • Structured refers to having a rheology that can confer stability on the personal care composition.
  • a degree of structure can be determined by characteristics determined by one or more of the following methods: Young's Modulus Method, Yield Stress Method, or Zero Shear Viscosity Method or by a Ultracentrifugation Method, described in U.S. Pat. No. 8,158,566, granted on Apr. 17, 2012.
  • a cleansing phase can be considered to be structured if the cleansing phase has one or more following characteristics: (a) Zero Shear Viscosity of at least 100 Pascal-seconds (Pa-s) , at least about 200 Pa-s, at least about 500 Pa-s, at least about 1,000 Pa-s, at least about 1,500 Pa-s, or at least about 2,000 Pa-s; (b) A Structured Domain Volume Ratio as measured by the Ultracentrifugation Method, of greater than about 40%, at least about 45%, at least about 50%, at least about 55%, at least about 60%, at least about 65%, at least about 70%, at least about 75%, at least about 80%, at least about 85%, or at least about 90%; or (c) A Young's Modulus of greater than about 2 Pascals (Pa) , greater than about 10 Pa, greater than about 20 Pa, greater than about 30 Pa, greater than about 40 Pa, greater than about 50 Pa, greater than about 75 Pa, or greater than about 100 Pa.
  • Pa-s Zero Shear Visco
  • “Lather” refers to an aerated foam which results from providing energy to aqueous surfactant mixtures, particularly dilute mixtures.
  • composition or method comprises less than about 5%, less than about 3%, less than about 1%, or even less than about 0.1%of the stated ingredient.
  • free of as used herein means that the composition or method comprises 0%of the stated ingredient that is the ingredient has not been added to the personal care composition. However, these ingredients may incidentally form as a byproduct or a reaction product of the other components of the personal care composition.
  • zinc-containing compounds in combination with a biocompatible surfactant and a lipid in single-phase or multi-phase applications to amenable skin can provide the benefit of improving the appearance of healthy skin or improving a condition such as atopic dermatitis, skin dysbiosis or acne.
  • compositions according to the disclosure include a zinc-containing compound, such as a zinc ionophore (e.g., zinc pyrithione) , a biocompatible surfactant and a lipid.
  • a zinc-containing compound such as a zinc ionophore (e.g., zinc pyrithione)
  • a biocompatible surfactant such as sodium EDTA, sodium EDTA, sodium EDTA, sodium metabisulfite, sodium metabisulfite, sodium metabisulfite, sodium metabisulfite, sodium metabisulfite, sodium metabisulfite, sodium metabisulfite, sodium metabisulfite, sodium metabisulfite, sodium metabisulfite, sodium metabisulfite, sodium metabisulfite, sodium metabisulfite, sodium metabisulfite, sodium metabisulfite, sodium metabisulfite, sodium metabisulfite, sodium metabisulfite, sodium metabisulfite, sodium metabisulfite
  • a method of enhancing skin appearance can comprise applying a zinc-containing compound such as a zinc ionophore (e.g., a zinc pyrithione or zinc pyridinethione) to the skin of an individual.
  • a method of treating an amenable skin condition such as atopic dermatitis (with or without lesions) , skin dysbiosis, or acne, can comprise applying a zinc-containing compound to the skin of an individual.
  • Examples of such zinc-containing compounds include, for example, zinc salts.
  • zinc salts useful herein include the following: zinc aluminate, zinc carbonate, zinc oxide, zinc phosphates, zinc selenide, zinc sulfide, zinc silicates, zinc silicofluoride, zinc borate, zinc hydroxide, zinc hydroxy sulfate, and combinations thereof.
  • the zinc-containing compound can comprise a zinc salt of 1-hydroxy-2-pyridinethione (known as "zinc pyrithione” or “ZPT” ) , for example, a mercaptopyridine-Noxide zinc salt.
  • ZPT can be made by reacting 1-hydroxy2-pyridinethione (i.e., pyrithione acid) or a soluble salt thereof with a zinc salt (e.g., zinc sulfate) to form a zinc pyrithione precipitate, as illustrated in U.S. Pat. No. 2,809,971, and the zinc pyrithione can be formed or processed into platelet ZPT using, for example, sonic energy as illustrated in U.S. Pat. No. 6,682,724.
  • Zinc pyrithione can take the form of particulates, platelets, or a combination thereof.
  • such particulates may have an average particle size from about 0.1 pm to about 20 pm; such particulates may also have an average particle size from about 0.2 pm to about 10 pm.
  • ZLM's zinc-containing layered materials
  • Examples of zinc-containing layered materials useful herein include zinc-containing layered structures with crystal growth primarily occurring in two dimensions. It is conventional to describe layer structures as not only those in which all the atoms are incorporated in well-defined layers, but also those in which there are ions or molecules between the layers, called gallery ions (A.F. Wells "Structural Inorganic Chemistry” Clarendon Press, 1975) .
  • Zinc-containing layered materials (ZLM's ) may have zinc incorporated in the layers and/or be components of the gallery ions. Many ZLMs occur naturally as minerals.
  • Natural ZLMs can also occur wherein anionic layer species such as clay-type minerals (e.g., phyllosilicates) contain ion-exchanged zinc gallery ions. All of these natural compounds can also be obtained synthetically or formed in situ in a composition or during a production process.
  • anionic layer species such as clay-type minerals (e.g., phyllosilicates) contain ion-exchanged zinc gallery ions. All of these natural compounds can also be obtained synthetically or formed in situ in a composition or during a production process.
  • ZLMs Another common class of ZLMs that are often, but not always, synthetic, is layered double hydroxides, which are generally represented by the formula [M 2+ 1-x M 3+ x (OH) 2 ] x+ A m- x/m+ nH 2 O and some or all of the divalent ions (M 2+ ) would be represented as zinc ions (Crepaldi, E L, Pava, P C, Tronto, J, Valim, J B J. Colloid Interfac. Sci. 2002, 248, 429-42) .
  • Zinc Carbonate Basic Cater Chemicals: Bensenville, Ill., USA
  • Zinc Carbonate Shepherd Chemicals: Norwood, Ohio, USA
  • Zinc Carbonate CPS Union Corp. : New York, N. Y., USA
  • Zinc Carbonate Elementis Pigments: Durham, UK
  • Zinc Carbonate AC Zinc Carbonate AC
  • Basic zinc carbonate which also may be referred to commercially as "Zinc Carbonate” or “Zinc Carbonate Basic” or “Zinc Hydroxy Carbonate” , is a synthetic version consisting of materials similar to naturally occurring hydrozincite.
  • the idealized stoichiometry is represented by Zn 5 (OH) 6 (CO 3 ) 2 but the actual stoichiometric ratios can vary slightly and other impurities may be incorporated in the crystal lattice.
  • pyrithione compounds include zinc pyrithione, sodium pyrithione, pyrithione acid, dipyrithione, chitosan pyrithione, magnesium disulfide pyrithione, and combinations thereof.
  • Pyrithione materials may also include other pyridinethione salts formed from heavy metals such as zinc, tin, cadmium, magnesium, aluminum, and zirconium.
  • a zinc-containing compound is applied to, and rinsed from, the skin of an individual at least once per day for several days.
  • Skin treated with a zinc-containing compound of the disclosure can show improvements in, for example, the appearance of the skin.
  • a zinc-containing compound can be applied at least once per day for about 14 days or more; or at least once per day for about 21 days or more.
  • the zinc-containing compound can be applied directly to the skin or provided as part of a rinse-off personal care composition, which is further described herein.
  • atopic dermatitis with or without lesions
  • skin dysbiosis or acne from about 0.1 ng/cm 2 to about 5.0 ng/cm 2 ; from about 0.2 ng/cm 2 to about 5.0 ng/cm 2 ; from about 0.5 ng/cm 2 to about 5.0 ng/cm 2 ; from about 1.0 ng/cm 2 to about 3.0 ng/cm 2 ; of a zinc-containing compound is deposited on the skin. Determination of the amount of zinc-containing compound deposited on the skin can be accomplished using techniques known in the art, such as the Cup Scrub method.
  • Improvements in skin appearance can be measured using known techniques, including, for example, a Corneometer.
  • typical Corneometer units range from about 15-20, wherein the higher the value the higher the level of skin moisturization; and the lower the value, the lower the level of moisturization. Methods for using a Corneometer are described below.
  • a zinc-containing compound e.g., zinc pyrithione
  • a measurement can be taken at predetermined time intervals to evaluate the effectiveness of the zinc-containing compound for improving the appearance of the skin, or for treating a skin with atopic dermatitis (with or without lesions) , skin dysbiosis or acne.
  • a Corneometer shows that about 3 hours after the 21 st application of the zinc-containing compound to the skin there is readily detectable improvement in skin appearance and/or an amenable skin condition (e.g., at least 0.3 Corneometer units) .
  • NMFs natural moisturizing factors
  • One suitable method of obtaining biological samples for measurement of skin NMFs is the application of tape to an epithelium. Any type of tape, including any type of medical tape, is suitable for use in obtaining biological samples of epithelia. This technique is well known in the art and is relatively simple to implement. The technique involves application of tape to the epithelial tissue, typically skin, followed by removal of the tape therefrom.
  • biomarker analytes obtained from the epithelial tissue and present on the tape can then be removed from the tape in any fashion that preserves the biomarker analytes for suitable detection and measurement assays.
  • Suitable biomarkers and testing procedures for NMFs are described in U.S. patent application Ser. No. 13/007,630.
  • While improvements in skin condition can be measured using a Corneometer or biomarkers are exemplary approaches to measuring and/or monitoring an amenable skin condition such as atopic dermatitis, skin dysbiosis, acne, or the appearance of healthy skin, but other suitable measuring and monitoring methods are available that focus on other properties of amenable skin conditions.
  • change in an amenable skin condition can be measured and/or monitored by assessing the visual dryness of skin, trans-epidermal water loss (TEWL) , total protein in the stratum corneum layer of skin, involucrin level in skin, HSA level in skin, lipid level in skin, relative differentiation of Keratins 1, 10 and 11 in skin, inflammatory cytokine (e.g., IL-1 ⁇ , IL-1r ⁇ , IL-8) level in skin, and histamine level in skin.
  • TEWL trans-epidermal water loss
  • a method of enhancing skin appearance also comprises at least one biocompatible surfactant.
  • the biocompatible surfactant can be anionic, non-ionic, amphoteric or zwitterionic, such as sodium laureth (n) sulfate, hereinafter SLEnS, wherein n defines the average moles of ethoxylation.
  • the n variable can range from about 1 to about 3.
  • Additional exemplary surfactants for use in the compositions of the disclosure include cocamidopropyl betaine, sodium lauroamphoacetate, sodium trideceth sulfate, and sodium cocoyl isethionate.
  • the personal care composition can further comprise from about 0.1%to 20%, by weight of the personal care composition, of a co-surfactant.
  • Co-surfactants according to the disclosure can comprise amphoteric surfactants, zwitterionic surfactants, or mixtures thereof.
  • the rinse-off personal care composition can include at least one of an amphoteric surfactant and a zwitterionic surfactant. Suitable amphoteric or zwitterionic surfactants include those described in U.S. Pat. No. 5,104,646 and U.S. Pat. No. 5,106,609.
  • Amphoteric surfactants can include those that can be broadly described as derivatives of aliphatic secondary and tertiary amines in which an aliphatic radical can be straight or branched chain and wherein an aliphatic substituent can contain from about 8 to about 18 carbon atoms such that one carbon atom can contain an anionic water solubilizing group, e.g., carboxy, sulfonate, sulfate, phosphate, or phosphonate.
  • an anionic water solubilizing group e.g., carboxy, sulfonate, sulfate, phosphate, or phosphonate.
  • Examples of compounds falling within this definition can be sodium 3-dodecyl-aminopropionate, sodium 3-dodecylaminopropane sulfonate, sodium lauryl sarcosinate, N-alkyltaurines such as the one prepared by reacting dodecylamine with sodium isethionate according to U.S. Pat. No. 2,658,072, N-higher alkyl aspartic acids such as those produced according to U.S. Pat. No. 2,438,091, and products described in U.S. Pat. No. 2,528,378.
  • amphoteric surfactants can include sodium lauroamphoacetate, sodium cocoamphoactetate, disodium lauroamphoacetate disodium cocodiamphoacetate, and mixtures thereof. Amphoacetates and diamphoacetates can also be used.
  • Zwitterionic surfactants suitable for use can include those that are broadly described as derivatives of aliphatic quaternary ammonium, phosphonium, and sulfonium compounds, in which aliphatic radicals can be straight or branched chains, and wherein an aliphatic substituent can contain from about 8 to about 18 carbon atoms such that one carbon atom can contain an anionic group, e.g., carboxy, sulfonate, sulfate, phosphate, or phosphonate.
  • Other zwitterionic surfactants can include betaines, including cocoamidopropyl betaine.
  • compositions of the disclosure also comprise a lipid.
  • Lipids according to the disclosure include any of a variety of natural or synthetic oils, fats or other generally hydrophobic compounds recognized in the art as lipids.
  • Exemplary lipids include glycerides suitable for use as hydrophobic skin benefit agents, including castor oil, safflower oil, corn oil, walnut oil, peanut oil, olive oil, cod liver oil, almond oil, avocado oil, palm oil, sesame oil, soybean oil, vegetable oils, sunflower seed oil, vegetable oil derivatives, coconut oil and derivatized coconut oil, cottonseed oil, derivatized cottonseed oil, jojoba oil, cocoa butter, petrolatum, mineral oil, and combinations thereof.
  • Non-limiting examples of alkyl esters suitable for use as lipid skin benefit agents herein include isopropyl esters of fatty acids and long chain esters of long chain (i.e., C10-C24) fatty acids, e.g., cetyl ricinoleate, nonlimiting examples of which include isopropyl palmitate, isopropyl myristate, cetyl riconoleate, and stearyl riconoleate.
  • hexyl laurate isohexyl laurate, myristyl myristate, isohexyl palmitate, decyl oleate, isodecyl oleate, hexadecyl stearate, decyl stearate, isopropyl isostearate, diisopropyl adipate, diisohexyl adipate, dihexyldecyl adipate, diisopropyl sebacate, acyl isononanoate lauryl lactate, myristyl lactate, cetyl lactate, and combinations thereof.
  • Non-limiting examples of alkenyl esters suitable for use as hydrophobic skin benefit agents herein include oleyl myristate, oleyl stearate, oleyl oleate, and combinations thereof.
  • Non-limiting examples of polyglycerin fatty acid esters suitable for use as lipid skin benefit agents include decaglyceryl distearate, decaglyceryl diisostearate, decaglyceryl monomyristate, decaglyceryl monolaurate, hexaglyceryl monooleate, and combinations thereof.
  • Non-limiting examples of lanolin and lanolin derivatives suitable for use as lipid skin benefit agents include lanolin, lanolin oil, lanolin wax, lanolin alcohols, lanolin fatty acids, isopropyl lanolate, acetylated lanolin, acetylated lanolin alcohols, lanolin alcohol linoleate, lanolin alcohol riconoleate, and combinations thereof.
  • Non-limiting examples of silicone oils suitable for use as lipid skin benefit agents include dimethicone copolyol, dimethylpolysiloxane, diethylpolysiloxane, mixed Cl -C30 alkyl polysiloxanes, phenyl dimethicone, dimethiconol, and combinations thereof.
  • Nonlimiting examples of silicone oils useful herein are described in U.S. Pat. No. 5,011,681.
  • hydrophobic skin benefit agents include milk triglycerides (e.g., hydroxylated milk glyceride) and polyol fatty acid olyesters.
  • Zinc-containing compounds can be applied to the skin through a rinse-off personal care composition. Suitable zinc-containing compounds are disclosed hereinabove.
  • a rinse-off personal care composition can be a single-phase composition or a multi-phase composition.
  • the rinse-off personal care composition can also involve a single-phase application or a multi-phase application that includes a cleansing phase and a benefit phase.
  • the cleansing phase and/or benefit phase can include the zinc-containing compound (e.g., zinc pyrithione) .
  • the cleansing phase can also include, for example, various biocompatible surfactants as described herein.
  • the benefit phase can comprise an effective amount of a lipid.
  • the cleansing phase and the benefit phase can be blended, and/or patterned.
  • the rinse-off personal care composition can comprise at least about 0.1%, by weight of the rinse-off personal care composition, of a zinc-containing compound (e.g., zinc pyrithione) .
  • the rinse-off personal care composition can also comprise from about 0.2%to about 1.0%, by weight of the rinse-off personal care composition, of a zinc-containing compound (e.g., zinc pyrithione) .
  • the rinse-off personal care composition can also comprise about 0.5%, by weight of the rinse-off personal care composition, of a zinc-containing compound (e.g., zinc pyrithione) .
  • a cleansing phase of a multi-phase composition according to the disclosure comprises a zinc-containing compound (e.g., a zinc ionophore such as zinc pyrithione) , as described herein.
  • the cleansing phase includes at least one biocompatible surfactant.
  • the cleansing phase can include an aqueous structured surfactant that is biocompatible.
  • the concentration of the structured surfactant in the personal care composition can range from about 1%to about 20%, by weight; from about 2%to about 15%, by weight; and from about 5%to about 10%, by weight of the personal care composition.
  • Such a structured surfactant can include sodium trideceth (n) sulfate, hereinafter STnS, wherein n defines the average moles of ethoxylation.
  • the n variable can range from about 0 to about 3.
  • the n variable can also range from about 0.5 to about 2.7, from about 1.1 to about 2.5, from about 1.8 to about 2.2, or n can be about 2.
  • STnS can provide improved stability, improved compatibility of benefit agents within the rinse-off personal care compositions, and increased mildness of the rinse-off personal care compositions.
  • the cleansing phase can comprise a structuring system, wherein the structuring system can comprise, optionally, a non-ionic emulsifier and an electrolyte.
  • the rinse-off personal care composition can be optionally free of sodium lauryl sulfate (SLS) , and can comprise at least a 70%lamellar structure.
  • SLS sodium lauryl sulfate
  • Suitable surfactants or co-surfactants that can generally be used in a cleansing phase for a rinse-off personal care composition are described hereinabove and/or in McCutcheon's : Detergents and Emulsifiers North American Edition (Allured Publishing Corporation 1947) (1986) , McCutcheon's , Functional Materials North American Edition (Allured Publishing Corporation 1973) (1992) and U.S. Pat. No. 3,929,678.
  • additives can optionally be included in the cleaning phase, including for example an emulsifier (e.g., non-ionic emulsifier) and electrolytes. Suitable emulsifiers and electrolytes are described in U.S. patent application Ser. No. 13/157,665.
  • rinse-off personal care compositions can include a benefit phase.
  • the benefit phase can be hydrophobic and/or anhydrous.
  • the benefit phase can also be substantially free of surfactant.
  • the benefit phase can also include a benefit agent.
  • the benefit phase can comprise from about 0.1%to about 50%, by weight of the rinse-off personal care composition, of the benefit agent.
  • the benefit phase can also include from about 0.5%to about 20%, by weight of the rinse-off personal care composition, of the benefit agent.
  • the benefit agent can include artificial sweat, castor oil, olive oil, oleic acid, 1618S, 1618U, petrolatum, glyceryl monooleate, mineral oil, natural oils (e.g., soybean oil) , and mixtures thereof.
  • Other suitable benefit agents are described in U.S. patent application Ser. No. 13/157,665.
  • the benefit phase can include a zinc-containing and/or pyrithione material (e.g., zinc pyrithione) .
  • zinc-containing materials can include, for example, zinc salts.
  • zinc salts useful can include the following: zinc aluminate, zinc carbonate, zinc oxide, zinc phosphates, zinc selenide, zinc sulfide, zinc silicates, zinc silicofluoride, zinc borate, zinc hydroxide, zinc hydroxy sulfate, and combinations thereof.
  • the benefit phase can also include additional ingredients as described below.
  • the benefit phase can typically comprise one or more benefit agents, as set forth above.
  • the benefit phase can comprise from about 0.1%to about 50%, by weight of the rinse-off personal care composition, of the benefit agent in the form of a lipid.
  • Additional ingredients can optionally be added to the rinse-off personal care composition for treatment of the skin, or to modify the aesthetics of the rinse-off personal care composition as is the case with perfumes, colorants, dyes or the like.
  • Optional materials useful in products herein can be categorized or described by their cosmetic and/or therapeutic benefit or their postulated mode of action or function. However, it can be understood that actives and other materials useful herein can, in some instances, provide more than one cosmetic and/or therapeutic benefit or function or operate via more than one mode of action. Therefore, classifications herein can be made for convenience and cannot be intended to limit an ingredient to particularly stated application or applications listed.
  • Optional materials can usually be formulated at about 6%or less, about 5%or less, about 4%or less, about 3%or less, about 2%or less, about 1%or less, about 0.5%or less, about 0.25%or less, about 0.1%or less, about 0.01%or less, or about 0.005%or less of the rinse-off personal care composition.
  • densities of separate phases can be adjusted such that they can be substantially equal.
  • low density microspheres can be added to one or more phases of the rinse-off personal care composition. Examples of rinse-off personal care compositions that comprise low density microspheres are described in U.S. Patent Publication No. 2004/0092415A1.
  • an optional benefit component that can be selected from the group consisting of thickening agents; preservatives; antimicrobials; fragrances; chelators (e.g., such as those described in U.S. Pat. No. 5,487,884 issued to Bisset, et al. ) ; sequestrants; vitamins (e.g. Retinol) ; vitamin derivatives (e.g., tocophenyl acetate, niacinamide, panthenol) ; sunscreens; desquamation actives (e.g., such as those described in U.S. Pat. Nos.
  • an optional benefit component that can be selected from the group consisting of thickening agents; preservatives; antimicrobials; fragrances; chelators (e.g., such as those described in U.S. Pat. No. 5,487,884 issued to Bisset, et al. ) ; sequestrants; vitamins (e.g. Retinol) ; vitamin derivatives (
  • anti-wrinkle/anti-atrophy actives e.g., N-acetyl derivatives, thiols, hydroxyl acids, phenol
  • anti-oxidants e.g., ascorbic acid derivatives, tocophenol
  • skin soothing agents/skin healing agents e.g., panthenoic acid derivatives, aloe vera, allantoin
  • skin lightening agents e.g., kojic acid, arbutin, ascorbic acid derivatives
  • skin tanning agents e.g., dihydroxyacetone
  • anti-acne medicaments essential oils
  • the multiphase personal care composition can comprise from about 0.1%to about 4%, by weight of the rinse-off personal care composition of hydrophobically modified titanium dioxide.
  • Other such suitable examples of such skin actives are described in U.S. patent application Ser. No. 13/157,665.
  • the Cup Scrub Procedure can be used to assist in determining how much zinc-containing compound (e.g., zinc ionophore such as zinc pyrithione) is deposited onto the skin of an individual.
  • zinc-containing compound e.g., zinc ionophore such as zinc pyrithione
  • test subjects receive a dose of 1 mL of body wash (via disposable syringe) to the volar forearm surface. The subjects proceed to generate lather on the volar forearm by rubbing the applied body wash with their opposite hand for approximately 15 seconds.
  • the lather is allowed to sit undisturbed on the skin for an additional 15 seconds.
  • the subjects rinse the arm for approximately 10 seconds, allowing the running water to contact the proximal volar forearm surface and cascade down (toward the distal surface) .
  • the subjects use a paper towel to pat the surface dry.
  • the next part of the procedure involves a 2-cm diameter glass cylinder containing a bead of silicone caulking on a skin contact edge that will be pressed firmly against a skin surface to prevent leakage of an extraction fluid.
  • One mL of the extraction solvent can be pipetted into the glass cylinder.
  • the extraction solvent can be 80: 20 0.05 M EDTA: Ethanol.
  • an entire area within the glass cylinder can be scrubbed for about 30 seconds using moderate pressure.
  • the solution can be removed and pipetted into a labeled glass sample vial.
  • the Cup Scrub Procedure can be repeated using fresh extraction solution, which will be pooled with the initial extraction in the labeled vial.
  • each cylinder and rod can be immersed in dilute solution and scrubbed with a finger or soft bristle brush.
  • the cylinders and rods can then be immersed in isopropyl alcohol (IPA) .
  • IPA isopropyl alcohol
  • cylinders and rods are wiped dry, e.g., with a Kimwipe or other lint free tissue, to remove any visible residue.
  • Scrub solutions can be changed at the end of each day or when any visible layer of residue can be found in the bottom thereof.
  • samples can be stored at 4°C ( ⁇ 3°C) until the samples are submitted for HPLC analysis. HPLC analysis is then used to determine the amount of deposition.
  • the free pyrithione in solution is then derivatized with 2-2'-Dithiopyridine, and subsequently analyzed via HPLC utilizing UV detection. The results are reported as ⁇ g of zinc pyrithione per mL of solution.
  • NMFs Natural Moisturizing Factors
  • Biomarkers that can be indicative of skin health can be measured to evaluate changes on one or more surfaces of epithelial tissue of a subject exposed to a product according to the disclosure.
  • biomarkers can allow for a relatively simple, efficient and quick determination of the usefulness of a product for providing one or more benefits to skin, or for monitoring changes in the skin upon or after exposure of the skin to a composition according to the disclosure.
  • Samples of epithelial tissue can be obtained to collect and analyze biomarker analytes.
  • suitable techniques for obtaining samples include application of tape, rinsing by lavage, biopsy, swabbing, scraping, blotting and combinations thereof. Whichever technique is used to obtain a sample, it should be one where the biomarkers obtained are those present on the surface and/or in the epithelial tissue, and not those in any of the underlying non-epithelial tissue, such as muscle.
  • a method of obtaining epithelial tissue is by application of tape, such as, but not limited to, any type of medical tape.
  • a technique for applying tape can be as straightforward as applying tape to the skin and then removing it.
  • Biomarker analytes obtained from the skin and present on the tape can be removed from the tape by any technique known in the art that preserves the biomarker analytes for suitable detection and measurement assays.
  • Examples of tapes can include, but are not limited to, D-squame and both of which are available from CuDerm Corporation, Dallas, Tex., USA; and tape, which is available from the 3M company, of Minnesota USA.
  • Biomarker analytes can be present in test and control samples and can be identified using one or more techniques known in the art. Detection techniques such as antibody-based binding methodologies, nucleotide probe-based specific hybridization assays, highly specific chemical tagging using markers, dyes, and other colorimetric and fluorometric probes and assays, , as well as enzyme-linked production of detectable labeled compounds can be used to detect and measure biomarker analytes.
  • biomarker analytes include inflammatory cytokines, natural moisturizing factors (NMFs) , keratin 1, keratin 10, keratin 11, lipids and total protein.
  • Exemplary biomarkers are natural moisturizing factors or NMFs.
  • NMFs include amino acids, lactic acid, urea, and pyrrolidone carboxylic acid (PCA) , and more particularly include Trans-Urocanic Acid, Citrulline, Glycine, Histidine, Ornithine, Proline, 2 Pyrrolidone 5 Acid, and Serine.
  • PCA pyrrolidone carboxylic acid
  • Trans-Urocanic Acid Citrulline
  • Glycine Glycine
  • Histidine Histidine
  • Ornithine Proline
  • 2 Pyrrolidone 5 Acid and Serine.
  • effectiveness of treatment with a composition of the disclosure can be evidenced by an increase in the amount of NMFs.
  • NMFs can be measured to detect improvement in skin appearance or reduction in the progression of an amenable skin condition in the form of atopic dermatitis (with or without lesions) , skin dysbiosis or acne. Such methodologies are further described in U.S.
  • NMF values the following methods can be used. Tape strips (D-Squame) from subjects are placed into polypropylene tubes and mixed, by vortex or sonication, with acidified water to extract relevant amino acid-related NMFs (glycine, histidine, proline, serine, urocanic acid, citrulline ornithine and 2-pyrrolidone5-carboxylic acid) . Extracts from the tape strips are spiked with stable-isotope internal standards of each NMF and then analyzed by gradient reversed-phase high-performance liquid chromatography with tandem mass spectrometry using multiple-reaction-monitoring.
  • relevant amino acid-related NMFs glycine, histidine, proline, serine, urocanic acid, citrulline ornithine and 2-pyrrolidone5-carboxylic acid
  • Combined standards for the NMFs are prepared over the required concentration range, spiked with the stable-isotope internal standards, and analyzed along with the samples.
  • the response ratio of each standard (response of standard/response of internal standard) for each NMF is plotted versus the standard concentration to generate a regression curve for each of the NMFs.
  • the concentration of each NMF in the extracts is then determined by interpolation from the appropriate regression standard curve.
  • Example 1 provides an analysis of the skin microbiota of a subject with atopic dermatitis.
  • Example 2 discloses a comparison of the skin microbiotas of a subject with atopic dermatitis and a healthy subject.
  • Example 3 shows the changes in diversity of skin microbiotas as healthy skin develops atopic dermatitis.
  • Example 4 reveals the measuring/monitoring of changes in the skin microbiota as an amenable skin condition such as atopic dermatitis is treated with a composition according to the disclosure.
  • the microbial load associated with the microbiota of skin having atopic dermatitis is heavier than the microbial load associated with healthy skin.
  • Use of zinc pyrithione in a body wash lowers the total bacterial level.
  • Samples of microbiotas from skin with atopic dermatitis were subjected to sequence analyses to identify the various genera present on the skin and to measure relative abundances.
  • read lengths of 150-800 bp were obtained using the Closed OTU picking method.
  • the Mega-blast search engine was used to interrogate the GG-13-8-91 database.
  • the second sequencing round yielded read lengths of 250-600 bp using the Cosed OTU picking method.
  • the Bowtie2 search engine was used to again interrogate the GG-13-8-91 database.
  • the third sequencing round involved read lengths of 250-600 bp being obtained using the Cosed OTU picking method.
  • the Bowtie2 search engine was used to interrogate the GG-13-8-97 database. Results are shown in Figure 1.
  • the data show that Staphylococcus is the predominant bacterial genus present in the skin microbiota of subjects with atopic dermatitis. Further, the data establish that the skin microbiota associated with atopic dermatitis comprises more than fourteen bacterial genera.
  • Staphylococcus aureus and Staphylococcus epidermidis are each present in greater relative abundance in atopic dermatitis skin microbiotas than in healthy skin microbiotas, and the relative abundances of each of these Staphylococcal species is greater in skin microbiotas of subjects with atopic dermatitis lesions than atopic dermatitis subjects without lesions.
  • Bacterial genera exhibiting this pattern of relative abundance include Streptococcus, Propionibacterium, Micrococcus and Corynebacterium. Mirroring the observations with the Staphylococcal species, each of the Streptococcus, Propionibacterium, Micrococcus and Corynebacterium genera are present in greater relative abundance in atopic dermatitis subjects with lesions than in atopic dermatitis subjects lacking lesions.
  • compositions of the disclosure comprise a zinc ionophore as a significant component, with zinc pyrithione being an exemplary zinc ionophore.
  • zinc pyrithione being an exemplary zinc ionophore.
  • the 11 identified bacterial genera were Staphylococcus, Streptococcus, Micrococcus, Corynebacterium, Kocuria, Propionibacterium, Rothia, Microbacterium, Paenibacillus, Paracoccus, and Deinococcus.
  • Skin samples were obtained from healthy subjects (designated "healthy” in Figure 4) as wells as subjects with atopic dermatitis lesions receiving a single wash ("AD. L" ) , subjects with atopic dermatitis but no visible lesions receiving a single wash ("AD. NL" ) , subjects with atopic dermatitis lesions receiving a four-week wash period ("AD.
  • the data show that zinc pyrithione is effective at the selective modulation or adjustment of bacterial genera relative abundances and that the zinc ionophore shifts the skin microbiota composition to one that more closely matches healthy skin, a sign that the therapeutic has a beneficial effect in modulating the skin microbiota of subjects with sound, but unhealthy, skin such as subjects with such skin disorders as atopic dermatitis, skin dysbiosis, or acne.
  • a related experiment assessing the treatment effects of a zinc ionophore on skin microbiota diversity in subjects with atopic dermatitis without lesions was performed to assess the effects of the therapeutic in this context.
  • the experimental design involved daily leg body washes of subjects with atopic dermatitis lacking visible lesions over a four-week period, with subjects engaging in daily washing with either B7U bar soap, vehicle alone (BCP2 base) , or 0.5%zinc pyrithione. Skin samples were again analyzed for microbiota composition by 16S rDNA sequencing with qPCR to quantify the abundances of the bacterial genera in the skin microbiotas.
  • compositions containing the zinc ionophore such as compositions containing a zinc ionophore (e.g., zinc pyrithione) , a biocompatible surfactant, and a lipid will not only affect the relative abundances of Staphylococcus, Streptococcus and Kocuria, but the additional bacterial genera identified in Example 4 (see Figure 4) .
  • a zinc ionophore e.g., zinc pyrithione
  • compositions according to the disclosure selectively reduce the relative abundance of some bacterial genera, notably Staphylococcus, and increase the relative abundance of other bacterial genera, and these selective effects on skin bacterial genera act to modulate the skin microbiota in a manner that restores a wild-type appearance to the skin microbiota in terms of diversity and relative abundances.
  • compositions according to the disclosure comprising a zinc ionophore (e.g., zinc pyrithione) , a biocompatible surfactant and a lipid delivered similar atopic dermatitis lesion improvement at significantly lower corticosteroid administration levels.
  • a zinc ionophore e.g., zinc pyrithione
  • a biocompatible surfactant e.g., sodium EDTA
  • a lipid e.g., sodium pyrithione
  • compositions comprising a zinc ionophore, e.g., zinc pyrithione, when used as a rinse-off body wash over a period of, e.g., four weeks, reversed the skin microbiota characteristics of skin with atopic dermatitis lesions (sound but unhealthy skin) and yielded a skin microbiota diversity more closely resembling the skin microbiota diversity of healthy skin.
  • a zinc ionophore e.g., zinc pyrithione
  • compositions comprising a zinc ionophore (e.g., zinc pyrithione) , a biocompatible surfactant, and a lipid provide a selective therapeutic useful in reducing the relative abundance of Staphylococcus and modulating the relative abundances of a number of other skin bacterial genera in treating conditions characterized by an aberrant skin microbiota diversity, such as atopic dermatitis, with or without lesions, skin dysbiosis, or acne.
  • a zinc ionophore e.g., zinc pyrithione
  • the data establish the value of assessing skin microbiota diversity in identifying a propensity or likelihood to develop the sound, but unhealthy, skin associated with a variety of skin disorders such as atopic dermatitis (with or without lesions) , skin dysbiosis, or acne.

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Abstract

L'invention concerne des matières et des méthodes permettant de modifier le microbiote cutané d'un sujet ayant une condition de peau appropriée. Les conditions de peau appropriées comprennent la peau saine et la peau présentant une dermatite atopique (avec ou sans lésions), une dysbiose cutanée et/ou de l'acné.
PCT/CN2016/098820 2016-09-13 2016-09-13 Méthodes de modification de la composition de la peau WO2018049557A1 (fr)

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US10712329B2 (en) 2017-07-03 2020-07-14 The Procter & Gamble Company Methods of measuring metal pollutants on skin
WO2020244898A1 (fr) 2019-06-06 2020-12-10 Unilever N.V. Composition topique destinée à restaurer la diversité microbienne d'une peau sensible au traitement
WO2020244962A1 (fr) 2019-06-06 2020-12-10 Unilever N.V. Composition topique destinée à rééquilibrer le microbiote cutané
US11906507B2 (en) 2020-03-24 2024-02-20 The Procter & Gamble Company Methods for testing skin samples

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Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US10712329B2 (en) 2017-07-03 2020-07-14 The Procter & Gamble Company Methods of measuring metal pollutants on skin
WO2020244898A1 (fr) 2019-06-06 2020-12-10 Unilever N.V. Composition topique destinée à restaurer la diversité microbienne d'une peau sensible au traitement
WO2020244962A1 (fr) 2019-06-06 2020-12-10 Unilever N.V. Composition topique destinée à rééquilibrer le microbiote cutané
US11906507B2 (en) 2020-03-24 2024-02-20 The Procter & Gamble Company Methods for testing skin samples

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