EP4161473A1 - Use of a compound containing two or more alcoholic hydroxyl groups or phenolic hydroxyl groups as a microbiome regulator on scalp - Google Patents

Use of a compound containing two or more alcoholic hydroxyl groups or phenolic hydroxyl groups as a microbiome regulator on scalp

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Publication number
EP4161473A1
EP4161473A1 EP20939406.3A EP20939406A EP4161473A1 EP 4161473 A1 EP4161473 A1 EP 4161473A1 EP 20939406 A EP20939406 A EP 20939406A EP 4161473 A1 EP4161473 A1 EP 4161473A1
Authority
EP
European Patent Office
Prior art keywords
scalp
glycol
compound
hydroxyl groups
microbiome regulator
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Withdrawn
Application number
EP20939406.3A
Other languages
German (de)
French (fr)
Other versions
EP4161473A4 (en
Inventor
Yi Shi
Mengmeng Zhang
Xiaowei Chang
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Henkel AG and Co KGaA
Original Assignee
Henkel AG and Co KGaA
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Henkel AG and Co KGaA filed Critical Henkel AG and Co KGaA
Publication of EP4161473A1 publication Critical patent/EP4161473A1/en
Publication of EP4161473A4 publication Critical patent/EP4161473A4/en
Withdrawn legal-status Critical Current

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q5/00—Preparations for care of the hair
    • A61Q5/006—Antidandruff preparations
    • 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
    • A61K8/33—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing oxygen
    • A61K8/35—Ketones, e.g. benzophenone
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
    • C12Q1/02—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving viable microorganisms
    • C12Q1/025—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving viable microorganisms for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2800/00—Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
    • A61K2800/40—Chemical, physico-chemical or functional or structural properties of particular ingredients
    • A61K2800/59—Mixtures
    • A61K2800/592—Mixtures of compounds complementing their respective functions
    • A61K2800/5922—At least two compounds being classified in the same subclass of A61K8/18
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12R—INDEXING SCHEME ASSOCIATED WITH SUBCLASSES C12C - C12Q, RELATING TO MICROORGANISMS
    • C12R2001/00—Microorganisms ; Processes using microorganisms
    • C12R2001/01—Bacteria or Actinomycetales ; using bacteria or Actinomycetales
    • C12R2001/44—Staphylococcus
    • C12R2001/45—Staphylococcus epidermidis
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2500/00—Screening for compounds of potential therapeutic value
    • G01N2500/10—Screening for compounds of potential therapeutic value involving cells

Definitions

  • the present invention relates to a use of a compound containing two or more alcoholic hydroxyl groups or phenolic hydroxyl groups and three to sixteen carbon atoms per molecule, as a microbiome regulator for selectively inhibiting Cutibacterium acnes and Staphylococcus epidermidis on scalp; a method of screening a compound or mixture for a microbiome regulator on scalp; and a shampoo or scalp serum composition comprising the microbiome regulator.
  • scalp itchiness is the most common scalp discomfort among people. In particular, it is the top scalp concern of Chinese consumers.
  • the itchiness is associated with scalp diseases, dandruff, psoriasis, etc., and many of non-dandruff consumers also suffered scalp itchiness.
  • the traditional ways to relieve scalp itchiness is to inhibit histamine release, or numb sensorial channels, or reduce redness with actives.
  • the traditional solutions are partial solutions to cure single symptoms and can merely cure symptoms in a short period.
  • they cannot satisfy the needs of the consumers, who are longing for novel solutions not only curing symptoms in a short period, but also remedying scalp to improve scalp overall condition in a long period.
  • the inventors conducted a lot of experiments and an intensive study, and surprisingly obtained a compound containing two or more alcoholic hydroxyl groups or phenolic hydroxyl groups and three to sixteen carbon atoms per molecule, which can be used as a microbiome regulator for selectively inhibiting Cutibacterium acnes and Staphylococcus epidermidis on scalp.
  • the present invention provides a use of a compound containing two or more alcoholic hydroxyl groups or phenolic hydroxyl groups and three to sixteen carbon atoms per molecule, as a microbiome regulator for selectively inhibiting Cutibacterium acnes and Staphylococcus epidermidis on scalp.
  • the present invention also provides a method of screening a compound or mixture for a microbiome regulator on scalp, comprising:
  • the present invention provides a shampoo or scalp serum composition, comprising a microbiome regulator for selectively inhibiting Cutibacterium acnes and Staphylococcus epidermidis on scalp, which is a compound containing two or more alcoholic hydroxyl groups or phenolic hydroxyl groups and three to sixteen carbon atoms per molecule, or the mixture thereof.
  • the use and the shampoo or scalp serum composition according to the present invention not only cure symptoms in a short period but also remedy scalp to improve scalp overall condition in a long period. Moreover, by the method according to the present invention, the use and the shampoo or scalp serum which not only cure symptoms in a short period but also remedy scalp to improve scalp overall condition in a long period can be obtained.
  • microbiome regulator and “microbiome balancer” are interchangeable, and they both refer to a substance which can regulate the ecological communities of commensal bacteria on the scalp, up-regulating good bacteria and down-regulating bad ones, and then in consequence improve the scalp condition holistically, with moisturized barrier, soothed redness, and relieved scalp itch.
  • Minimum Inhibitory Concentration can be abbreviated to “MIC” ; and it refers to the minimum concentration of a chemical that will inhibit the growth of a microorganism, and is usually reported as ⁇ g/ml or mg/ml for a solid compound, and as percentage value for a liquid compound.
  • MIC Minimum Inhibitory Concentration
  • the “Minimum Inhibitory Concentration” in the present invention is measured according to the method as described in the Examples of the present description.
  • Minimum Inhibitory Concentration (Cutibacterium acnes) of the compound or mixture” and “Minimum Inhibitory Concentrations of the compound or mixture towards Cutibacterium acnes” are interchangeable, and they both refer to the minimum concentration of the compound or mixture that will inhibit the growth of Cutibacterium acnes.
  • Minimum Inhibitory Concentration (Staphylococcus epidermidis) of the compound or mixture” and “Minimum Inhibitory Concentrations of the compound or mixture towards Staphylococcus epidermidis” are interchangeable, and they both refer to the minimum concentration of the compound or mixture that will inhibit the growth of Staphylococcus epidermidis.
  • a compound containing two or more alcoholic hydroxyl groups or phenolic hydroxyl groups and three to sixteen carbon atoms per molecule can be used as a microbiome regulator for selectively inhibiting Cutibacterium acnes and Staphylococcus epidermidis on scalp.
  • the compound containing two or more alcoholic hydroxyl groups or phenolic hydroxyl groups and three to sixteen carbon atoms per molecule has a ratio of Minimum Inhibitory Concentration (Cutibacterium acnes) to Minimum Inhibitory Concentration (Staphylococcus epidermidis) ⁇ 1.
  • the ratio of Minimum Inhibitory Concentration (Cutibacterium acnes) to Minimum Inhibitory Concentration (Staphylococcus epidermidis) is not more than 0.9, not more than 0.8, not more than 0.7, not more than 0.6, not more than 0.5, not more than 0.4, not more than 0.3, not more than 0.25, or not more than 0.20.
  • the ratio of Minimum Inhibitory Concentration (Cutibacterium acnes) to Minimum Inhibitory Concentration (Staphylococcus epidermidis) is at least 0.01, at least 0.02, or at least 0.025.
  • the ratio of Minimum Inhibitory Concentration (Cutibacterium acnes) to Minimum Inhibitory Concentration (Staphylococcus epidermidis) is in a range of 0.01 to 1, preferably 0.02 to 0.9, more preferably 0.025 to 0.5.
  • Minimum Inhibitory Concentration Cutibacterium acnes
  • Minimum Inhibitory Concentration Staphylococcus epidermidis
  • the ratio of Minimum Inhibitory Concentration (Cutibacterium acnes) to Minimum Inhibitory Concentration (Staphylococcus epidermidis) is less than 0.01, it will lead to an imbalance of the bacterium.
  • the compound containing two or more alcoholic hydroxyl groups or phenolic hydroxyl groups and three to sixteen carbon atoms per molecule contains two, three, four or five alcoholic hydroxyl groups or phenolic hydroxyl groups per molecule.
  • the compound contains two, three or four alcoholic hydroxyl groups or phenolic hydroxyl groups per molecule. More preferably, the compound contains two alcoholic hydroxyl groups or four phenolic hydroxyl groups per molecule.
  • the compound is selected from the group consisting of propylene glycol, butylene glycol, pentylene glycol, hexylene glycol, caprylyl glycol, decylene glycol, dipropylene glycol, glycerin, ethylhexylglycerin and phloretin.
  • the compound is selected from the group consisting of pentylene glycol, hexylene glycol, caprylyl glycol, decylene glycol, ethylhexylglycerin and phloretin.
  • Examples of commercially available compound according to the present invention include, for example, SymClariol, which is decylene glycol available from Symrise Company; Caprylyl Glycol, which is available from Symrise Company; Pentylene Glycol, which is available from Symrise Company; EthylHexylGlycerin, which is available from Schülke & Mayr GmbH; and Phloretin, which is Phloretin available from Symrise Company.
  • a method of screening a compound or mixture for a microbiome regulator on scalp comprises:
  • a shampoo or scalp serum composition comprises a microbiome regulator for selectively inhibiting Cutibacterium acnes and Staphylococcus epidermidis on scalp, which is a compound containing two or more alcoholic hydroxyl groups or phenolic hydroxyl groups and three to sixteen carbon atoms per molecule, or the mixture thereof.
  • the mircobiome regulator is the compound containing two or more alcoholic hydroxyl groups or phenolic hydroxyl groups and three to sixteen carbon atoms per molecule as defined above, or the mixture thereof.
  • the amount of the microbiome regulator is at least 0.01 wt. %, at least 0.05%, at least 0.1 wt. %, at least 0.5%, or at least 1.0%.
  • the amount of the microbiome regulator is not more than 15.0 wt. %, not more than 14 wt. %, not more than 13 wt. %, not more than 12 wt. %, not more than 11 wt. %, or not more than 10 wt. %.
  • the amount of the microbiome regulator is within a range of 0.01 wt.
  • %to 15.0 wt. % preferably 0.5 wt. %to 13 wt. %, more preferably 1 wt. %to 10 wt. %, based on the total weight of the shampoo or scalp serum composition. If the amount of the microbiome regulator is less than 0.01 wt. %based on the total weight of the shampoo or scalp serum composition, the composition cannot effectively cure symptoms in a short period and remedy scalp to improve scalp overall condition in a long period. If the amount of the microbiome regulator is higher than 15.0 wt. %based on the total weight of the shampoo or scalp serum composition, the formulation will be not stable in a long term and the efficacy delivery of the microbiome regulator will be lower.
  • the microbiome regulator contains two alcoholic hydroxyl groups or four phenolic hydroxyl groups per molecule.
  • the microbiome regulator is selected from the group consisting of propylene glycol, butylene glycol, pentylene glycol, hexylene glycol, caprylyl glycol, decylene glycol, dipropylene glycol, glycerin, ethylhexylglycerin and phloretin.
  • the microbiome regulator is selected from the group consisting of pentylene glycol, hexylene glycol, caprylyl glycol, decylene glycol, ethylhexylglycerin, glycerin and phloretin.
  • the microbiome regulator contains ethylhexylglycerin, decylene glycol and glycerin. More preferably, the microbiome regulator further contains 1, 2-hexanediol and/or propylene glycol.
  • the shampoo or scalp serum composition according to the present invention may be formulated to contain one or more additional components or additives besides those described above.
  • the shampoo composition may additionally comprise a solvent, a surfactant, a thickener, a hair conditioning agent and/or PH adjuster; and the scalp serum composition may additionally comprise a solvent, a thickener, a hair conditioning agent and/or PH adjuster.
  • the solvent which can be used in the practice of the present invention can be any solvent conventionally used in the shampoo or scalp serum, and it is preferably Aqua.
  • the surfactants which can be used in the practice of the present invention include, but are not limited to:
  • Anionic surfactants for example, Acylated Amino Acids, such as Sodium Lauroyl Sarcosinate, and TEA-Cocoyl Glutamate; Carboxylic Acids &salts, such as Sodium Laureth-13 Carboxylate; Sulfonic Acid derivatives, such as Sodium Methyl Cocoyl Taurate, Sodium Cocoyl Isethionate, and Sodium C14-16 Olefin Sulfonate; Sulfuric Acid derivatives, such as Sodium Laureth Sulfate, and Ammonium Lauryl Sulfate;
  • Acylated Amino Acids such as Sodium Lauroyl Sarcosinate, and TEA-Cocoyl Glutamate
  • Carboxylic Acids &salts such as Sodium Laureth-13 Carboxylate
  • Sulfonic Acid derivatives such as Sodium Methyl Cocoyl Taurate, Sodium Cocoyl Isethionate, and Sodium C14-16 Olef
  • Nonionic surfactants for example, Alkyl Glucosides, such as Coco-Glucoside and Lauryl Glucoside; and Amine oxides, such as Lauramine Oxide;
  • Amphoteric surfactants for example, Alkyl amido Alkyl Amines, such as Sodium Lauroamphoacetate; and Alkyl Betaines, such as Cocamidopropyl betaine, Coco-betaine and coco-hydroxysultaine.
  • thickener which can be used for shampoo in the practice of the present invention include, but are not limited to PEG/PPG-120/10 Trimethylolpropane Trioleate, PEG-120 Methyl Glucose Dioleate, PEG-150 Distearate, PEG-150 Pentaerythrityl Tetrastearate, PEG-55 Propylene Glycol Oleate, PPG-2 Hydroxyethyl Cocamide, Laureth-2, Cocamide MEA and NaCl.
  • the PH adjuster which can be used in the practice of the present invention includes, but are not limited to citric acid, lactic acid, sodium hydroxide, and potassium hydroxide.
  • the shampoo or scalp serum composition according to the present invention can be made by any appropriate method.
  • the composition can be made by simply mixing all the components together.
  • the shampoo composition can be produced by a method comprising: heating water in a vessel; mixing the surfactants into the water; heating the mixture until the surfactants are fully dispersed; adding the thickener, hair conditioning agents, microbiome regulator and/or PH adjuster and/or other optional components with continuous stirring until all the components are fully dissolved; and cooling down the final mixture to room temperature.
  • the scalp serum composition can be produced by a method comprising: mixing the thickener, PH adjuster into water with continuous stirring until a homogeneous gel formed without flocs and lumps; adding hair conditioning agents, microbiome regulator and/or other optional components with continuous stirring until all the components are fully dispersed.
  • the shampoo or scalp serum composition can be in solid or liquid state.
  • the shampoo can be used in the form of viscous liquid.
  • the serum can be used in either gel form or liquid form.
  • the shampoo composition can be applied gently on wet hair, and then the hair is rinsed thoroughly.
  • the shampoo composition may be used as often as desired.
  • the scalp serum composition can be applied evenly over scalp, the scalp can be gently massaged for 2-3 minutes until the composition is fully absorbed, and there is no need to rinse or towel-wipe after use.
  • the scalp serum composition may be used whenever there are any discomforts on scalp.
  • the compound containing two or more alcoholic hydroxyl groups or phenolic hydroxyl groups and three to sixteen carbon atoms per molecule according to the present invention can be used as a microbiome regulator for selectively inhibiting Cutibacterium acnes and Staphylococcus epidermidis on scalp, and it can be used for not only curing symptoms in a short period but also remedying scalp to improve scalp overall condition in a long period
  • the compound containing two or more alcoholic hydroxyl groups or phenolic hydroxyl groups and three to sixteen carbon atoms per molecule can be obtained.
  • the shampoo or scalp serum composition according to the present invention can not only cure symptoms in a short period but also remedies scalp to improve scalp overall condition in a long period.
  • SymClariol which is decylene glycol, was manufactured by Symrise Company.
  • Caprylyl Glycol was manufactured by Symrise Company.
  • Pentylene Glycol was manufactured by Symrise Company.
  • Sensiva SC 50 which is EthylHexylGlycerin was manufactured by Schülke & Mayr GmbH.
  • Phloretin which is Phloretin, was manufactured by Symrise Company.
  • LIPACIDE C8G which is Capryloyl Glycine, was manufactured by Seppic Company.
  • Sphingony which is Sphinganine, was manufactured by Evonik Company.
  • BIOXYNE which is Quaternium-73, was manufactured by Sethic Company.
  • Phenoxyethanol was manufactured by BASF.
  • Propionibacterium acnes ATCC6919 was purchased from Shanghai Fuxiang Biotechnology Co., Ltd.
  • Staphylococcus epidermidis ATCC12228 was purchased from the mall North Natronian Biotechnology Co., Ltd.
  • the solid medium was prepared after being cooled to about 60 °C and poured into a clean sterilization plate.
  • the amount of liquid added was about 1/4-1/3 of the anaerobic bottle. Fully purged with nitrogen to remove oxygen and sterilized at 115 °C as preparation.
  • Cutibacterium acnes (cultured for 3 ⁇ 5 days, anaerobically) with a sterile syringe, transferred it to a culture flask containing 1/3 volume of ground beef in fresh broth, and kept anaerobic at 37 °C. After 3 to 5 days of culture, it could be passaged or used for subsequent experiments.
  • the antibacterial activity of the test substance against Cutibacterium acnes was evaluated by the micro-broth dilution method recommended by the American Association of Clinical and Laboratory Standards (see Dej-Adisai S, Meechai I, Puripattanavong J, Kummee S. Antityrosinase and antimicrobial activities from Thai medicinal plants. Arch Pharm Res, 2014, 37 (4) : 473-483; and Guo M, Lu Y, Yang J, Zhao X, Lu Y. Inhibitory effects of Schisandra chinensis extract on acne-related inflammation and UVB-induced photoageing. Pharmaceutical Biology, 2016, 54 (12) : 2987-2994) to determine the minimum inhibitory concentration (MIC) of the test substance against Cutibacterium acnes.
  • MIC minimum inhibitory concentration
  • the lyophilized powder was taken out from the refrigerator, resuscitated according to the species instructions, and cultured at 105 rpm with a constant temperature of 37 °C. After 1-2 days of culture, transferred a small amount of bacterial liquid to fresh liquid medium. Generally cultured for 3 generations after resuscitation, it could be used for subsequent experiments.
  • the solid powder sample to be tested was first dissolved in DMSO (completely dissolved) , and then filtered through a 0.22 ⁇ M microporous membrane. Diluted twice with the corresponding culture solution, and the appropriate concentration was prepared according to the supplier's recommended amount (DMSO is less than 1%) .
  • the insoluble sample was directly diluted with a medium to prepare a suspension, and the liquid sample was diluted with a medium by volume concentration.
  • the sample solution needed to be prepared right before use. This process needed to be performed aseptically in a clean bench.
  • the 96-well plate was sealed with a parafilm, wrapped in a fresh-keeping bag, and cultured at 37 °C, 105 rpm for 24 h, and the OD value at 530 nm was measured by a microplate reader.
  • the positive drug is: penicillin.
  • Three sets of parallel experiments were conducted. The minimum inhibitory concentration (MIC) was defined as the lowest concentration of the test substance at which bacterial growth was completely inhibited.
  • the direct values of Minimum Inhibitory Concentration (Cutibacterium acnes) and Minimum Inhibitory Concentration (Staphylococcus epidermidis) of all the tested samples were obtained. Then, the calculated values of ( (Minimum Inhibitory Concentration (Cutibacterium acnes) /Minimum Inhibitory Concentration (Staphylococcus epidermidis) ) of all the tested samples were obtained. If the calculated value of a sample is less than 1, the sample is suitable as a microbiome regulator on scalp; whereas if the calculated value of a sample is equal to or higher than 1, the sample is not suitable as a microbiome regulator.
  • the compound containing two or more alcoholic hydroxyl groups or phenolic hydroxyl groups and three to sixteen carbon atoms per molecule can be used as a microbiome regulator for selectively inhibiting Cutibacterium acnes and Staphylococcus epidermidis on scalp.
  • the compounds of Inventive Examples 1-5 can be used as microbiome regulator for selectively inhibiting Cutibacterium acnes and Staphylococcus epidermidis on scalp
  • the compounds of Comparative Examples 1-6 which contain one hydroxyl group, eighteen carbon atoms, no hydroxyl group, one hydroxyl group, no hydroxyl group and twenty-three carbon atoms, and one hydroxyl group per molecule, respectively
  • the compounds of Comparative Examples 1-6 which contain one hydroxyl group, eighteen carbon atoms, no hydroxyl group, one hydroxyl group, no hydroxyl group and twenty-three carbon atoms, and one hydroxyl group per molecule, respectively
  • composition of Example 1 10 subjects were shampooed with the composition of Example 1 every the other day, that is three times shampoos in total. For each shampooing, the composition of Example 1 was applied twice, 6g of each application.
  • Example 2 which is a leave-on serum, it was applied on blow-dried scalp of another 10 subjects after washing, 4 g each subject. During the course, the composition of Example 2 was also applied three times in total.
  • compositions according to the present invention not only cure scalp itchiness &redness to the subject in this short period but also remedy scalp with improved scalp moisture and reduced inflammation securing a healthy scalp condition in a long run.

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Abstract

Use of a compound containing two or more alcoholic hydroxyl groups or phenolic hydroxyl groups and three to sixteen carbon atoms per molecular, as microbiome regulator for selectively inhibiting Cutibacterium acnes and Staphylococcus epidermidis on scalp. A method of screening a compound or mixture for a microbiome regulator on scalp, comprising: testing Minimum Inhibitory Concentrations of the compound or mixture towards Cutibacterium acnes and Staphylococcus epidermidis, respectively; obtaining direct values of Minimum Inhibitory Concentration (Cutibacterium acnes) and Minimum Inhibitory Concentration (Staphylococcus epidermidis) of the compound or mixture, respectively; obtaining a calculated value of ( (Minimum Inhibitory Concentration (Cutibacterium acnes) /Minimum Inhibitory Concentration (Staphylococcus epidermidis) ) of the compound or mixture from the above direct values; and determining that the compound or mixture is suitable as a microbiome regulator on scalp, if the calculated value <1; whereas the compound or mixture is not suitable as a microbiome regulator on scalp, if the calculated value > = 1. A shampoo or scalp serum composition, comprising a microbiome regulator for selectively inhibiting Cutibacterium acnes and Staphylococcus epidermidis on scalp, which is a compound containing two or more alcoholic hydroxyl groups or phenolic hydroxyl groups and three to sixteen carbon atoms per molecule, or the mixture thereof.

Description

    Use of a compound containing two or more alcoholic hydroxyl groups or phenolic hydroxyl groups as a microbiome regulator on scalp Technical field
  • The present invention relates to a use of a compound containing two or more alcoholic hydroxyl groups or phenolic hydroxyl groups and three to sixteen carbon atoms per molecule, as a microbiome regulator for selectively inhibiting Cutibacterium acnes and Staphylococcus epidermidis on scalp; a method of screening a compound or mixture for a microbiome regulator on scalp; and a shampoo or scalp serum composition comprising the microbiome regulator.
    • Background of the invention
  • Consumers are having increasing awareness and concerns about the scalp problems, like itchiness, redness, dryness, etc. As is known to all, scalp itchiness is the most common scalp discomfort among people. In particular, it is the top scalp concern of Chinese consumers. The itchiness is associated with scalp diseases, dandruff, psoriasis, etc., and many of non-dandruff consumers also suffered scalp itchiness. The traditional ways to relieve scalp itchiness is to inhibit histamine release, or numb sensorial channels, or reduce redness with actives.
  • However, the traditional solutions are partial solutions to cure single symptoms and can merely cure symptoms in a short period. Thus, nowadays they cannot satisfy the needs of the consumers, who are longing for novel solutions not only curing symptoms in a short period, but also remedying scalp to improve scalp overall condition in a long period.
  • Therefore, there is a need to develop a solution of scalp care which not only cures symptoms in a short period but also remedies scalp to improve scalp overall condition in a long period, and a method for obtaining such a solution.
  • Summary of the invention
  • It is an object of the present invention to provide a solution of scalp care which not only cures symptoms in a short period but also remedies scalp to improve scalp overall condition in a long period. It is another object of the present invention is to provide a method for obtaining such a solution.
  • The inventors found that dysbalanced bacteria is proved associated with abnormal scalp conditions, and thus, a scalp care solution can be developed by regulating bacteria. Moreover, they found that targeting on scalp commensal bacterial is more effective than the traditional solutions; and it gives scalp a holistic remedy at once not only altering microbial communities but also improving  physiological conditions to reach a balanced microenvironment to improve the scalp condition holistically, with moisturized barrier, soothed redness, and relieved scalp itch.
  • Based on the above findings, the inventors conducted a lot of experiments and an intensive study, and surprisingly obtained a compound containing two or more alcoholic hydroxyl groups or phenolic hydroxyl groups and three to sixteen carbon atoms per molecule, which can be used as a microbiome regulator for selectively inhibiting Cutibacterium acnes and Staphylococcus epidermidis on scalp.
  • Accordingly, the present invention provides a use of a compound containing two or more alcoholic hydroxyl groups or phenolic hydroxyl groups and three to sixteen carbon atoms per molecule, as a microbiome regulator for selectively inhibiting Cutibacterium acnes and Staphylococcus epidermidis on scalp.
  • The present invention also provides a method of screening a compound or mixture for a microbiome regulator on scalp, comprising:
  • -- testing Minimum Inhibitory Concentrations of the compound or mixture towards Cutibacterium acnes and Staphylococcus epidermidis, respectively;
  • -- obtaining direct values of Minimum Inhibitory Concentration (Cutibacterium acnes) and Minimum Inhibitory Concentration (Staphylococcus epidermidis) of the compound or mixture, respectively;
  • -- obtaining a calculated value of ( (Minimum Inhibitory Concentration (Cutibacterium acnes) /Minimum Inhibitory Concentration (Staphylococcus epidermidis) ) of the compound or mixture from the above direct values; and
  • -- determining that the compound or mixture is suitable as a microbiome regulator on scalp, if the calculated value <1; whereas the compound or mixture is not suitable as a microbiome regulator on scalp, if the calculated value > = 1.
  • Furthermore, the present invention provides a shampoo or scalp serum composition, comprising a microbiome regulator for selectively inhibiting Cutibacterium acnes and Staphylococcus epidermidis on scalp, which is a compound containing two or more alcoholic hydroxyl groups or phenolic hydroxyl groups and three to sixteen carbon atoms per molecule, or the mixture thereof.
  • The use and the shampoo or scalp serum composition according to the present invention not only cure symptoms in a short period but also remedy scalp to improve scalp overall condition in a long period. Moreover, by the method according to the present invention, the use and the shampoo or scalp serum which not only cure symptoms in a short period but also remedy scalp to improve scalp overall condition in a long period can be obtained.
    • Detailed description of the invention
  • It is to be understood by one of ordinary skill in the art that the present discussion is a description of exemplary embodiments only, and is not intended as limiting the broader aspects of the present invention. Each aspect so described may be combined with any other aspect or aspects unless clearly indicated to the contrary. In particular, any feature indicated as being preferred or advantageous may be combined with any other feature or features indicated as being preferred or advantageous.
  • Unless specified otherwise, in the context of the present invention, the terms used are to be construed in accordance with the following definitions.
  • Unless specified otherwise, all wt%values quoted herein are percentages by weight based on total weight of the shampoo or scalp serum composition.
  • Unless specified otherwise, as used herein, the singular forms “a” , “an” and “the” include both singular and plural referents.
  • The terms “comprising” and “comprises” as used herein are synonymous with “including” , “includes” or “containing” , “contains” , and are inclusive or open-ended and do not exclude additional, non-recited members, elements or process steps.
  • Unless specified otherwise, the recitation of numerical end points includes all numbers and fractions subsumed within the respective ranges, as well as the recited end points.
  • Unless specified otherwise, as used herein, terms “microbiome regulator” and “microbiome balancer” are interchangeable, and they both refer to a substance which can regulate the ecological communities of commensal bacteria on the scalp, up-regulating good bacteria and down-regulating bad ones, and then in consequence improve the scalp condition holistically, with moisturized barrier, soothed redness, and relieved scalp itch.
  • Unless specified otherwise, as used therein, a term “Minimum Inhibitory Concentration” can be abbreviated to “MIC” ; and it refers to the minimum concentration of a chemical that will inhibit the growth of a microorganism, and is usually reported as μg/ml or mg/ml for a solid compound, and as percentage value for a liquid compound. The “Minimum Inhibitory Concentration” in the present invention is measured according to the method as described in the Examples of the present description.
  • The expression “Minimum Inhibitory Concentration (Cutibacterium acnes) of the compound or mixture” and “Minimum Inhibitory Concentrations of the compound or mixture towards Cutibacterium acnes” are interchangeable, and they both refer to the minimum concentration of the compound or mixture that will inhibit the growth of Cutibacterium acnes. The expression “Minimum Inhibitory Concentration (Staphylococcus epidermidis) of the compound or mixture” and “Minimum Inhibitory Concentrations of the compound or mixture towards Staphylococcus epidermidis” are interchangeable, and they both refer to the minimum concentration of the compound or mixture that will inhibit the growth of Staphylococcus epidermidis.
  • Unless otherwise defined, all terms used in the disclosing the invention, including technical and scientific terms, have the meaning as commonly understood by one of the ordinary skill in the art to which this invention belongs.
  • According to the present invention, surprisingly, a compound containing two or more alcoholic hydroxyl groups or phenolic hydroxyl groups and three to sixteen carbon atoms per molecule, can be used as a microbiome regulator for selectively inhibiting Cutibacterium acnes and Staphylococcus epidermidis on scalp.
  • In an aspect of the present invention, the compound containing two or more alcoholic hydroxyl groups or phenolic hydroxyl groups and three to sixteen carbon atoms per molecule has a ratio of Minimum Inhibitory Concentration (Cutibacterium acnes) to Minimum Inhibitory Concentration (Staphylococcus epidermidis) <1. Preferably, the ratio of Minimum Inhibitory Concentration (Cutibacterium acnes) to Minimum Inhibitory Concentration (Staphylococcus epidermidis) is not more than 0.9, not more than 0.8, not more than 0.7, not more than 0.6, not more than 0.5, not more than 0.4, not more than 0.3, not more than 0.25, or not more than 0.20. Preferably, the ratio of Minimum Inhibitory Concentration (Cutibacterium acnes) to Minimum Inhibitory Concentration (Staphylococcus epidermidis) is at least 0.01, at least 0.02, or at least 0.025. In a preferred embodiment, the ratio of Minimum Inhibitory Concentration (Cutibacterium acnes) to Minimum Inhibitory Concentration (Staphylococcus epidermidis) is in a range of 0.01 to 1, preferably 0.02 to 0.9, more preferably 0.025 to 0.5. If the ratio of Minimum Inhibitory Concentration (Cutibacterium acnes) to Minimum Inhibitory Concentration (Staphylococcus epidermidis) is equal to or higher than 1, the compound cannot be effectively used as the microbiome regulator for selectively inhibiting Cutibacterium acnes and Staphylococcus epidermidis on scalp. If the ratio of Minimum Inhibitory Concentration (Cutibacterium acnes) to Minimum Inhibitory Concentration (Staphylococcus epidermidis) is less than 0.01, it will lead to an imbalance of the bacterium.
  • In another aspect of the present invention, the compound containing two or more alcoholic hydroxyl groups or phenolic hydroxyl groups and three to sixteen carbon atoms per molecule contains two, three, four or five alcoholic hydroxyl groups or phenolic hydroxyl groups per molecule. Preferably,  the compound contains two, three or four alcoholic hydroxyl groups or phenolic hydroxyl groups per molecule. More preferably, the compound contains two alcoholic hydroxyl groups or four phenolic hydroxyl groups per molecule.
  • Preferably, the compound is selected from the group consisting of propylene glycol, butylene glycol, pentylene glycol, hexylene glycol, caprylyl glycol, decylene glycol, dipropylene glycol, glycerin, ethylhexylglycerin and phloretin. Among others, more preferably, the compound is selected from the group consisting of pentylene glycol, hexylene glycol, caprylyl glycol, decylene glycol, ethylhexylglycerin and phloretin.
  • Examples of commercially available compound according to the present invention include, for example, SymClariol, which is decylene glycol available from Symrise Company; Caprylyl Glycol, which is available from Symrise Company; Pentylene Glycol, which is available from Symrise Company; EthylHexylGlycerin, which is available from Schülke &Mayr GmbH; and  Phloretin, which is Phloretin available from Symrise Company.
  • According to the present invention, a method of screening a compound or mixture for a microbiome regulator on scalp comprises:
  • -- testing Minimum Inhibitory Concentrations of the compound or mixture towards Cutibacterium acnes and Staphylococcus epidermidis, respectively;
  • -- obtaining direct values of Minimum Inhibitory Concentration (Cutibacterium acnes) and Minimum Inhibitory Concentration (Staphylococcus epidermidis) of the compound or mixture, respectively;
  • -- obtaining a calculated value of ( (Minimum Inhibitory Concentration (Cutibacterium acnes) /Minimum Inhibitory Concentration (Staphylococcus epidermidis) ) of the compound or mixture from the above direct values; and
  • -- determining that the compound or mixture is suitable as a microbiome regulator on scalp, if the calculated value <1; whereas the compound or mixture is not suitable as a microbiome regulator on scalp, if the calculated value > = 1.
  • As mentioned above, all the Minimum Inhibitory Concentrations are measured according to the method as described in the Examples of the present description.
  • According to the present invention, a shampoo or scalp serum composition comprises a microbiome regulator for selectively inhibiting Cutibacterium acnes and Staphylococcus epidermidis on scalp, which is a compound containing two or more alcoholic hydroxyl groups or phenolic hydroxyl groups and three to sixteen carbon atoms per molecule, or the mixture thereof.
  • In an aspect of the shampoo or scalp serum composition according to the present invention, the mircobiome regulator is the compound containing two or more alcoholic hydroxyl groups or phenolic hydroxyl groups and three to sixteen carbon atoms per molecule as defined above, or the mixture thereof.
  • In another aspect of the present invention, based on the total weight of the shampoo or scalp serum composition, the amount of the microbiome regulator is at least 0.01 wt. %, at least 0.05%, at least 0.1 wt. %, at least 0.5%, or at least 1.0%. On the other hand, based on the total weight of the shampoo or scalp serum composition, the amount of the microbiome regulator is not more than 15.0 wt. %, not more than 14 wt. %, not more than 13 wt. %, not more than 12 wt. %, not more than 11 wt. %, or not more than 10 wt. %. In a preferred embodiment, the amount of the microbiome regulator is within a range of 0.01 wt. %to 15.0 wt. %, preferably 0.5 wt. %to 13 wt. %, more preferably 1 wt. %to 10 wt. %, based on the total weight of the shampoo or scalp serum composition. If the amount of the microbiome regulator is less than 0.01 wt. %based on the total weight of the shampoo or scalp serum composition, the composition cannot effectively cure symptoms in a short period and remedy scalp to improve scalp overall condition in a long period. If the amount of the microbiome regulator is higher than 15.0 wt. %based on the total weight of the shampoo or scalp serum composition, the formulation will be not stable in a long term and the efficacy delivery of the microbiome regulator will be lower.
  • In a preferred embodiment, the microbiome regulator contains two alcoholic hydroxyl groups or four phenolic hydroxyl groups per molecule. In an embodiment of the present invention, the microbiome regulator is selected from the group consisting of propylene glycol, butylene glycol, pentylene glycol, hexylene glycol, caprylyl glycol, decylene glycol, dipropylene glycol, glycerin, ethylhexylglycerin and phloretin. In another embodiment of the present invention, the microbiome regulator is selected from the group consisting of pentylene glycol, hexylene glycol, caprylyl glycol, decylene glycol, ethylhexylglycerin, glycerin and phloretin. Preferably, the microbiome regulator contains ethylhexylglycerin, decylene glycol and glycerin. More preferably, the microbiome regulator further contains 1, 2-hexanediol and/or propylene glycol.
  • The shampoo or scalp serum composition according to the present invention may be formulated to contain one or more additional components or additives besides those described above. For example, the shampoo composition may additionally comprise a solvent, a surfactant, a thickener, a hair conditioning agent and/or PH adjuster; and the scalp serum composition may additionally comprise a solvent, a thickener, a hair conditioning agent and/or PH adjuster.
  • The solvent which can be used in the practice of the present invention can be any solvent conventionally used in the shampoo or scalp serum, and it is preferably Aqua.
  • The surfactants which can be used in the practice of the present invention include, but are not limited to:
  • Anionic surfactants, for example, Acylated Amino Acids, such as Sodium Lauroyl Sarcosinate, and TEA-Cocoyl Glutamate; Carboxylic Acids &salts, such as Sodium Laureth-13 Carboxylate; Sulfonic Acid derivatives, such as Sodium Methyl Cocoyl Taurate, Sodium Cocoyl Isethionate, and Sodium C14-16 Olefin Sulfonate; Sulfuric Acid derivatives, such as Sodium Laureth Sulfate, and Ammonium Lauryl Sulfate;
  • Nonionic surfactants, for example, Alkyl Glucosides, such as Coco-Glucoside and Lauryl Glucoside; and Amine oxides, such as Lauramine Oxide;
  • Amphoteric surfactants, for example, Alkyl amido Alkyl Amines, such as Sodium Lauroamphoacetate; and Alkyl Betaines, such as Cocamidopropyl betaine, Coco-betaine and coco-hydroxysultaine.
  • Examples of thickener which can be used for shampoo in the practice of the present invention include, but are not limited to PEG/PPG-120/10 Trimethylolpropane Trioleate, PEG-120 Methyl Glucose Dioleate, PEG-150 Distearate, PEG-150 Pentaerythrityl Tetrastearate, PEG-55 Propylene Glycol Oleate, PPG-2 Hydroxyethyl Cocamide, Laureth-2, Cocamide MEA and NaCl.
  • Examples of thickener which can be used for serum in the practice of the present invention include, but are not limited to (meth) acrylates, (meth) acrylate crosspolymer, Carbomer, Acrylates/C10-30 Alkyl Acrylate Crosspolymer, Hydroxyethylcellulose, Xanthan Gum and Gellan Gum.
  • The PH adjuster which can be used in the practice of the present invention includes, but are not limited to citric acid, lactic acid, sodium hydroxide, and potassium hydroxide.
  • The shampoo or scalp serum composition according to the present invention can be made by any appropriate method. For example, the composition can be made by simply mixing all the components together.
  • In fact, there are no particular restrictions on the production methods of the shampoo or scalp serum composition of the present invention, as long as the method complies with a conventional method for producing the shampoo or scalp serum composition. For example, the shampoo composition can be produced by a method comprising: heating water in a vessel; mixing the surfactants into the water; heating the mixture until the surfactants are fully dispersed; adding the thickener, hair conditioning agents, microbiome regulator and/or PH adjuster and/or other optional components with continuous stirring until all the components are fully dissolved; and cooling down the final mixture to room temperature. The scalp serum composition can be produced by a method comprising: mixing the thickener, PH adjuster into water with continuous stirring until a homogeneous gel formed without flocs and lumps; adding hair conditioning agents, microbiome regulator and/or other optional components with continuous stirring until all the components are fully dispersed.
  • There are also no particular restrictions on the equipment for preparing the shampoo or scalp serum, as long as the equipment can prepare the shampoo or scalp serum composition of the present invention.
  • The shampoo or scalp serum composition can be in solid or liquid state. The shampoo can be used in the form of viscous liquid. The serum can be used in either gel form or liquid form.
  • The shampoo composition can be applied gently on wet hair, and then the hair is rinsed thoroughly. The shampoo composition may be used as often as desired.
  • The scalp serum composition can be applied evenly over scalp, the scalp can be gently massaged for 2-3 minutes until the composition is fully absorbed, and there is no need to rinse or towel-wipe after use. The scalp serum composition may be used whenever there are any discomforts on scalp.
  • The compound containing two or more alcoholic hydroxyl groups or phenolic hydroxyl groups and three to sixteen carbon atoms per molecule according to the present invention can be used as a microbiome regulator for selectively inhibiting Cutibacterium acnes and Staphylococcus epidermidis on scalp, and it can be used for not only curing symptoms in a short period but also remedying scalp to improve scalp overall condition in a long period
  • By the method of screening a compound or mixture for a microbiome regulator on scalp according to the present invention, the compound containing two or more alcoholic hydroxyl groups or phenolic hydroxyl groups and three to sixteen carbon atoms per molecule can be obtained.
  • The shampoo or scalp serum composition according to the present invention can not only cure symptoms in a short period but also remedies scalp to improve scalp overall condition in a long period.
  • Examples
  • I. In-vitro Tests
  • 1. Tested Samples
  • The following samples were tested in the examples.
  • SymClariol, which is decylene glycol, was manufactured by Symrise Company.
  • Caprylyl Glycol was manufactured by Symrise Company.
  • Pentylene Glycol was manufactured by Symrise Company.
  • Sensiva SC 50, which is EthylHexylGlycerin was manufactured by Schülke &Mayr GmbH.
  • Phloretin, which is Phloretin, was manufactured by Symrise Company.
  • LIPACIDE C8G, which is Capryloyl Glycine, was manufactured by Seppic Company.
  • Sphingony, which is Sphinganine, was manufactured by Evonik Company.
  • Sodium Benzoate was manufactured by Wuhan Youji Industries Co..
  • Methyparaben was manufactured by Clariant GmbH.
  • BIOXYNE, which is Quaternium-73, was manufactured by Sethic Company.
  • Phenoxyethanol was manufactured by BASF.
  • 2. Laboratory apparatuses
  • The main experimental instruments used in the test process were shown in Table 1.
  • Table 1 Main experimental instruments
  • 3. Experimental Materials
  • 3.1 Bacterial strain
  • Propionibacterium acnes ATCC6919 was purchased from Shanghai Fuxiang Biotechnology Co., Ltd., and Staphylococcus epidermidis ATCC12228 was purchased from the mall North Natronian Biotechnology Co., Ltd.
  • 3.2 Experimental test sample and main reagents
  • The main experimental reagents used in the test procedure were shown in Table 2.
  • Table 2 Main Experimental Reagents
  • 3.3 Medium formulas
  • The formulations of the mediums used in the test procedure were shown in Tables 3 and 4.
  • Table 3 Staphylococcus epidermidis solid medium formula
  • Reagent name Dosage (unit)
    Beef extract 3 g
    Peptone 10 g
    NaCl 5 g
    Agar 15 g
    Distilled water 1 L
  • Note: The liquid medium (pH =7.0) was not with agar and sterilized at 121 ℃. The solid medium was prepared after being cooled to about 60 ℃ and poured into a clean sterilization plate.
  • Table 4 Formula of Cutibacterium acnes liquid medium
  • Note: The amount of liquid added was about 1/4-1/3 of the anaerobic bottle. Fully purged with nitrogen to remove oxygen and sterilized at 115 ℃ as preparation.
  • 4. Experimental methods
  • 4.1 Screening for antibacterial activity against Cutibacterium acnes
  • 4.1.1 Cutibacterium acnes resuscitation steps:
  • a. Took out the lyophilized tube stored in the refrigerator at 4 ℃, wiped the outer wall with 75% ethanol, circled the fine end with a grinding wheel, and opened the lyophilized tube.
  • b. Pipetted about 1 mL of sterile water into a lyophilized tube, mixing by pipetting, and injected it into an anaerobic culture flask.
  • c. It could be passaged after being cultured for 3 to 5 days in a constant temperature incubator at 37 ℃. After 3 generations of general recovery, it could be used in subsequent experiments.
  • 4.1.2 Cutibacterium acnes cryopreservation steps::
  • a. Anaerobic cultured 3 d Cutibacterium acnes together with the ground meat-containing medium were transferred to a 50 mL centrifuge tube and centrifuged at 1000 rpm.
  • b. Transferred the supernatant remaining after centrifugation to a new 50 mL centrifuge tube, discarded the following minced sediment, centrifuged at 2500 rpm for 5 min, and discarded the supernatant.
  • c. Added the autoclaved skim milk, blow evenly, dispensed into a sterile freeze-dried tube about 0.5 mL per lyophilized tube, and wrapped it with 8 layers of sterile gauze.
  • d. Stored the lyophilized tube in a refrigerator at 4 ℃ for 15 min, then froze in a -20 ℃ refrigerator for 20 min, then transferred to a -80 ℃ refrigerator overnight.
  • e. Transferred the lyophilized tube to the activated freeze dryer and pumped until the sample was dry in the lyophilized tube.
  • f. Removed the lyophilized tubes and sealed them with an external flame of alcohol lamp.
  • g. Marked the name of the bacteria on the lyophilized tube and the date of freezing, and stored it in a refrigerator at 4 ℃.
  • 4.1.3 Cutibacterium acnes culture and passage
  • Pipetted about 1 mL of Cutibacterium acnes (cultured for 3～5 days, anaerobically) with a sterile syringe, transferred it to a culture flask containing 1/3 volume of ground beef in fresh broth, and kept anaerobic at 37 ℃. After 3 to 5 days of culture, it could be passaged or used for subsequent experiments.
  • 4.1.4 Micro-broth method to test the antibacterial activity of the test substance against Cutibacterium acnes
  • The antibacterial activity of the test substance against Cutibacterium acnes was evaluated by the micro-broth dilution method recommended by the American Association of Clinical and Laboratory Standards (see Dej-Adisai S, Meechai I, Puripattanavong J, Kummee S. Antityrosinase and antimicrobial activities from Thai medicinal plants. Arch Pharm Res, 2014, 37 (4) : 473-483; and Guo M, Lu Y, Yang J, Zhao X, Lu Y. Inhibitory effects of Schisandra chinensis extract on acne-related inflammation and UVB-induced photoageing. Pharmaceutical Biology, 2016, 54 (12) : 2987-2994) to determine the minimum inhibitory concentration (MIC) of the test substance against Cutibacterium acnes.
  • Investigated the MIC of Cutibacterium acnes at different concentrations of the test substance. The specific steps were as follows:
  • a. Centrifugally harvest Cutibacterium acnes (cultured for 3 d, anaerobically) , washed 3 times with PBS buffer, and adjusted the bacterial concentration to 2 × 10 8 CFU /mL, then diluted to 1.25 × 10 6 CFU /mL with fresh cooked meat medium.
  • b. Diluted the test substance with the meat medium to a concentration of 2 times the final concentration.
  • c. Added 100 μL of medium containing different concentrations of test substance and 100 μL of medium containing Cutibacterium acnes to a sterile 96-well plate, and treated with penicillin and chloramphenicol as a positive control, with no drug treatment as negative control, without Cutibacterium acnes containing medium alone as a blank control. Cultured anaerobically at 37 ℃ for 24 h.
  • d. After the end of the culture, the growth inhibition of Cutibacterium acnes was detected by a microplate reader evaluating the OD value (absorbance) at 600 nm. The minimum concentration of the test substance when Cutibacterium acnes growth was completely inhibited was the minimum inhibitory concentration (MIC) .
  • 4.2 Screening for antibacterial activity against Staphylococcus epidermidis
  • 4.2.1 Staphylococcus epidermis resuscitation, subculture steps:
  • On the ultra-clean workbench, the lyophilized powder was taken out from the refrigerator, resuscitated according to the species instructions, and cultured at 105 rpm with a constant temperature of 37 ℃. After 1-2 days of culture, transferred a small amount of bacterial liquid to fresh liquid medium. Generally cultured for 3 generations after resuscitation, it could be used for subsequent experiments.
  • 4.2.2 Staphylococcus epidermis cryopreservation steps:
  • Took the solution after 1 day of culture, add 20%of the final volume of glycerin, mixed and froze it to -20 ℃.
  • 4.2.3 Preparation of bacterial suspension:
  • The bacterial suspension 12 hours after passage was taken, and the bacterial solution was diluted with a new culture solution to a concentration of 1.0×10 4 to 1.0×10 6 CFU/mL.
  • 4.2.4 Preparation of the sample to be tested:
  • The solid powder sample to be tested was first dissolved in DMSO (completely dissolved) , and then filtered through a 0.22 μM microporous membrane. Diluted twice with the corresponding culture solution, and the appropriate concentration was prepared according to the supplier's recommended amount (DMSO is less than 1%) . The insoluble sample was directly diluted with a medium to prepare a suspension, and the liquid sample was diluted with a medium by volume concentration. The sample solution needed to be prepared right before use. This process needed to be performed aseptically in a clean bench.
  • 4.2.5 Loading and measuring:
  • Opened the sterile 96-well plate in the clean bench, added 200 μL of the culture solution to each well as the blank control group, added 100 μL of positive drug solution and 100 μL of the bacterial suspension to each well of the positive control group. For the sample solution to be tested, added 100 μL of the bacterial suspension and 100 μL of different concentration test sample solution to each well of the test group. 100 μL of the culture solution and 100 μL of the test sample solution were added to each well of the negative control group. 100 μL of the culture solution and 100 μL of the bacterial suspension were added to each well of the growth control group. The 96-well plate was sealed with a parafilm, wrapped in a fresh-keeping bag, and cultured at 37 ℃, 105 rpm for 24 h, and the OD value at 530 nm was measured by a microplate reader. The positive drug is: penicillin. Three sets of parallel experiments were conducted. The minimum inhibitory concentration (MIC) was defined as the lowest concentration of the test substance at which bacterial growth was completely inhibited.
  • According to the above methods, the direct values of Minimum Inhibitory Concentration (Cutibacterium acnes) and Minimum Inhibitory Concentration (Staphylococcus epidermidis) of all the tested samples were obtained. Then, the calculated values of ( (Minimum Inhibitory Concentration (Cutibacterium acnes) /Minimum Inhibitory Concentration (Staphylococcus epidermidis) ) of all the tested samples were obtained. If the calculated value of a sample is less than 1, the sample is suitable as a microbiome regulator on scalp; whereas if the calculated value of a sample is equal to or higher than 1, the sample is not suitable as a microbiome regulator.
  • The direct values and the calculated values of all the tested samples were shown in Table 5.
  • Table 5
  • As shown in Table 1, it is obvious that the compound containing two or more alcoholic hydroxyl groups or phenolic hydroxyl groups and three to sixteen carbon atoms per molecule, according to the present invention can be used as a microbiome regulator for selectively inhibiting Cutibacterium acnes and Staphylococcus epidermidis on scalp. In particular, it can be seen that the compounds of Inventive Examples 1-5 (all of which contain two or more alcoholic hydroxyl groups or phenolic hydroxyl groups and three to sixteen carbon atoms per molecule according to the present invention) can be used as microbiome regulator for selectively inhibiting Cutibacterium acnes and Staphylococcus epidermidis on scalp, whereas the compounds of Comparative Examples 1-6 (which contain one hydroxyl group, eighteen carbon atoms, no hydroxyl group, one hydroxyl group, no hydroxyl group and twenty-three carbon atoms, and one hydroxyl group per molecule, respectively) cannot be used as microbiome regulator for selectively inhibiting Cutibacterium acnes and Staphylococcus epidermidis on scalp.
  • II. Clinical Tests
  • The following two compositions as shown in Tables 6 and 7 were tested.
  • Table 6 Shampoo composition of Example 1
  • Table 7 Scalp serum composition of Example 2
  • 20 subjects troubled with scalp itchiness but not diagnosed of dandruff had completed a 6-day clinical study.
  • For the composition of Example 1, 10 subjects were shampooed with the composition of Example 1 every the other day, that is three times shampoos in total. For each shampooing, the composition of Example 1 was applied twice, 6g of each application.
  • For the composition of Example 2, which is a leave-on serum, it was applied on blow-dried scalp of another 10 subjects after washing, 4 g each subject. During the course, the composition of Example 2 was also applied three times in total.
  • The evaluation of scalp condition was implemented before and after the 6-day treatment. From the results, it can be seen that the compositions according to the present invention not only cure scalp itchiness &redness to the subject in this short period but also remedy scalp with improved scalp moisture and reduced inflammation securing a healthy scalp condition in a long run.

Claims (15)

  1. Use of a compound containing two or more alcoholic hydroxyl groups or phenolic hydroxyl groups and three to sixteen carbon atoms per molecule, as a microbiome regulator for selectively inhibiting Cutibacterium acnes and Staphylococcus epidermidis on scalp.
  2. The use according to claim 1, wherein the compound has a ratio of Minimum Inhibitory Concentration (Cutibacterium acnes) to Minimum Inhibitory Concentration (Staphylococcus epidermidis) <1.
  3. The use according to claim 1 or 2, wherein the compound contains two alcoholic hydroxyl groups or four phenolic hydroxyl groups per molecule.
  4. The use according to claim 1 or 2, wherein the compound is selected from the group consisting of propylene glycol, butylene glycol, pentylene glycol, hexylene glycol, caprylyl glycol, decylene glycol, dipropylene glycol, glycerin, ethylhexylglycerin and phloretin.
  5. The use according to any one of claims 1 to 4, wherein the compound is selected from the group consisting of pentylene glycol, hexylene glycol, caprylyl glycol, decylene glycol, ethylhexylglycerin and phloretin.
  6. A method of screening a compound or mixture for a microbiome regulator on scalp, comprising:
    -- testing Minimum Inhibitory Concentrations of the compound or mixture towards Cutibacterium acnes and Staphylococcus epidermidis, respectively;
    -- obtaining direct values of Minimum Inhibitory Concentration (Cutibacterium acnes) and Minimum Inhibitory Concentration (Staphylococcus epidermidis) of the compound or mixture, respectively;
    -- obtaining a calculated value of ( (Minimum Inhibitory Concentration (Cutibacterium acnes) /Minimum Inhibitory Concentration (Staphylococcus epidermidis) ) of the compound or mixture from the above direct values; and
    -- determining that the compound or mixture is suitable as a microbiome regulator on scalp, if the calculated value <1; whereas the compound or mixture is not suitable as a microbiome regulator on scalp, if the calculated value > = 1.
  7. A shampoo or scalp serum composition, comprising a microbiome regulator for selectively inhibiting Cutibacterium acnes and Staphylococcus epidermidis on scalp, which is a compound containing two or more alcoholic hydroxyl groups or phenolic hydroxyl groups and three to sixteen carbon atoms per molecule, and the mixture thereof.
  8. The composition according to claim 7, wherein the shampoo composition further comprises a solvent, a surfactant, a thickener, a hair conditioning agent and/or a PH adjuster.
  9. The composition according to claim 7, wherein the scalp serum composition further comprises a solvent, a thickener, a hair conditioning agent and/or a PH adjuster.
  10. The composition according to any one of claims 7 to 9, wherein the amount of the microbiome regulator is within a range of 0.005 wt. %to 15.0 wt. %, preferably 5 wt. %to 10 wt. %, based on the total weight of the composition.
  11. The composition according to any one of claims 7 to 9, wherein the microbiome regulator contains two alcoholic hydroxyl groups or four phenolic hydroxyl groups per molecule.
  12. The composition according to any one of claims 7 to 9, wherein the microbiome regulator is selected from the group consisting of propylene glycol, butylene glycol, pentylene glycol, hexylene glycol, caprylyl glycol, decylene glycol, dipropylene glycol, glycerin, ethylhexylglycerin and phloretin.
  13. The composition according to any one of claims 7 to 9, wherein the microbiome regulator is selected from the group consisting of pentylene glycol, hexylene glycol, caprylyl glycol, decylene glycol, ethylhexylglycerin, glycerin and phloretin.
  14. The composition according to any one of claims 7 to 9, wherein the microbiome regulator contains ethylhexylglycerin, decylene glycol and glycerin.
  15. The composition according to claim 14, wherein the microbiome regulator further contains 1, 2-hexanediol and/or propylene glycol.
EP20939406.3A 2020-06-05 2020-06-05 USE OF A COMPOUND CONTAINING TWO OR MORE ALCOHOLIC HYDROXYL GROUPS OR PHENOLIC HYDROXYL GROUPS AS A MICROBIOME REGULATOR ON THE SCALP Withdrawn EP4161473A4 (en)

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