WO2017138003A1 - Compositions de conservateur antimicrobien - Google Patents

Compositions de conservateur antimicrobien Download PDF

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Publication number
WO2017138003A1
WO2017138003A1 PCT/IL2017/050177 IL2017050177W WO2017138003A1 WO 2017138003 A1 WO2017138003 A1 WO 2017138003A1 IL 2017050177 W IL2017050177 W IL 2017050177W WO 2017138003 A1 WO2017138003 A1 WO 2017138003A1
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WO
WIPO (PCT)
Prior art keywords
formulation
thymol
phenoxyethanol
linalool
organic solvent
Prior art date
Application number
PCT/IL2017/050177
Other languages
English (en)
Inventor
Paul Salama
Ariel GLIKSBERG
Tali LEVINTOOL
Original Assignee
Sharon Laboratories Ltd.
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Filing date
Publication date
Application filed by Sharon Laboratories Ltd. filed Critical Sharon Laboratories Ltd.
Publication of WO2017138003A1 publication Critical patent/WO2017138003A1/fr

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    • 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
    • A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
    • A61K31/215—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
    • A61K31/22—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N31/00—Biocides, pest repellants or attractants, or plant growth regulators containing organic oxygen or sulfur compounds
    • A01N31/02—Acyclic compounds
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N31/00—Biocides, pest repellants or attractants, or plant growth regulators containing organic oxygen or sulfur compounds
    • A01N31/08—Oxygen or sulfur directly attached to an aromatic ring system
    • 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
    • A61K31/045—Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates
    • 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
    • A61K31/045—Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates
    • A61K31/05—Phenols
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/02—Cosmetics or similar toiletry preparations characterised by special physical form
    • A61K8/0208—Tissues; Wipes; Patches
    • 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
    • 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
    • A61K8/34—Alcohols
    • A61K8/347—Phenols
    • 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
    • A61K8/37—Esters of carboxylic acids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2/00—Methods or apparatus for disinfecting or sterilising materials or objects other than foodstuffs or contact lenses; Accessories therefor
    • A61L2/16—Methods or apparatus for disinfecting or sterilising materials or objects other than foodstuffs or contact lenses; Accessories therefor using chemical substances
    • A61L2/18—Liquid substances or solutions comprising solids or dissolved gases
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2/00—Methods or apparatus for disinfecting or sterilising materials or objects other than foodstuffs or contact lenses; Accessories therefor
    • A61L2/16—Methods or apparatus for disinfecting or sterilising materials or objects other than foodstuffs or contact lenses; Accessories therefor using chemical substances
    • A61L2/22—Phase substances, e.g. smokes, aerosols or sprayed or atomised substances
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2/00—Methods or apparatus for disinfecting or sterilising materials or objects other than foodstuffs or contact lenses; Accessories therefor
    • A61L2/16—Methods or apparatus for disinfecting or sterilising materials or objects other than foodstuffs or contact lenses; Accessories therefor using chemical substances
    • A61L2/23—Solid substances, e.g. granules, powders, blocks, tablets
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L9/00—Disinfection, sterilisation or deodorisation of air
    • A61L9/01—Deodorant compositions
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q17/00—Barrier preparations; Preparations brought into direct contact with the skin for affording protection against external influences, e.g. sunlight, X-rays or other harmful rays, corrosive materials, bacteria or insect stings
    • A61Q17/005—Antimicrobial preparations
    • 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
    • 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
    • A61K2800/10—General cosmetic use
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
    • Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
    • Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Definitions

  • the present invention in some embodiments thereof, relates to personal care formulations and, more particularly, but not exclusively, to stable personal care formulations with antimicrobial activity, articles containing same, and uses thereof in, for example, reducing or preventing growth of microorganisms .
  • Antimicrobial compositions are used, for example, in the health care industry, food service industry, meat processing industry, and in the private sector by individual consumers.
  • Infection is a constant risk to any healthy person, and poses even a higher risk to hospitalized patients.
  • the risk of infection is further increased when the natural infection barriers of skin or other epithelial surfaces are breached during a surgical procedure, and/or otherwise in cases where bacteria normally present on the skin or in the air are allowed to access the interior surfaces of the body.
  • antibacterial cleansing compositions typically contain an active antibacterial agent, a surfactant, and various other ingredients, for example, dyes, fragrances, pH adjusters, thickeners, and the like, in an aqueous carrier.
  • Nosocomial infections caused by antibiotic -resistant bacteria result in patient suffer and mortality and impose a substantial burden on the medical system due to extended periods of hospitalization.
  • the economic impact of managing infections caused by nosocomial infections is substantial, and costs are estimated to be more than $4 billion annually.
  • European patent 2,209,392 discloses preservatives and antimicrobial agents comprising extracts derived from sugar cane.
  • the present inventors have surprisingly uncovered that personal care formulations comprising thymol and linalool, phenoxyethanol or phenyl ethyl alcohol at specified ratios, can be readily prepared, and that such formulations exhibit exceptional and even synergistic antimicrobial activity.
  • the present invention provides a formulation comprising: thymol, an organic solvent and an odor masking agent selected from the group consisting of: linalool and liffarome.
  • the thymol and organic solvent are in a ratio that ranges from 1: 1 to 15:85, by weight, respectively.
  • the thymol and odor masking agent are in a ratio that ranges from 100:0.1 to 1: 1, by weight, respectively.
  • the thymol and linalool are in a ratio that ranges from 95:5 to 1: 1, by weight, respectively.
  • the thymol and liffarome are in a ratio that ranges from 100:0.1 to 4: 1, by weight, respectively.
  • the organic solvent is selected from the group consisting of: propylene glycol, benzyl alcohol, phenyl ethyl alcohol, phenoxyethanol, each being substituted or non- substituted, or a mixture thereof. In some embodiments, said organic solvent is effective as an antibacterial agent. In some embodiments, said organic solvent is an alcohol.
  • the organic solvent is phenyl ethyl alcohol. In some embodiments, the organic solvent is phenoxyethanol. In some embodiments, the organic solvent is benzyl alcohol.
  • the formulation comprises liffarome
  • the organic solvent is selected from the group consisting of: phenoxyethanol or phenyl ethyl alcohol.
  • the formulation comprises liffarome and further comprises capric acid.
  • the formulation comprises: 15 - 35 % (w/w) thymol; 3 - 20% linalool
  • the organic solvent ranges from 40% to 80%, by weight, respectively.
  • the thymol and linalool are in a ratio that ranges from 80:20 to 60:40, by weight.
  • the formulation comprises: 15 - 35 % (w/w) thymol; 65- 85 % (w/w) phenoxyethanol or phenyl ethyl alcohol; and 0.1 - 3 % (w/w) liffarome. In some embodiments, the formulation further comprises 1 -5 % (w/w) capric acid.
  • the phenoxyethanol or phenyl ethyl alcohol range from 40% to 80%, by weight, respectively.
  • the thymol and phenoxyethanol or phenyl ethyl alcohol are in a ratio that ranges from 80:20 to 60:40, by weight.
  • the formulation is a synergistic antimicrobial formulation.
  • the formulation is for use in the treatment of a medical, cosmetic and/or cosmeceutical condition.
  • the present invention provides an article comprising the disclosed formulation.
  • the article is a personal care product.
  • the product is or comprises a formulation in the form selected from the group consisting of: paste, cream, lotion, foam, gel, emulsion, an ointment, and soap.
  • the article is selected from the group consisting of: a fabric, a bandage, a wipe, a pledget, a swab, a suppository, a dressing, a solution, a mousse, a pad, and a patch.
  • the article is identified for use in the treatment of a condition selected from medical, cosmetic and cosmeceutical condition.
  • the present invention provides a method of inhibiting or reducing the formation of load of a microorganism in and/or on an article, the method comprising contacting said article with the disclosed formulation.
  • the microorganism is selected from bacteria, molds and fungi.
  • the bacteria are Gram positive bacteria selected from the group consisting of: Staphylococcus aureus, Staphylococcus epidermidis, and Bacillus cereus; or Gram negative bacteria selected from the group consisting of: Escherichia coli, Pseudomonas aeuruginosa, and Burkholderia cepacia.
  • the fungi are selected from the group consisting of: Candida albicans.
  • the mold is Aspergillus niger.
  • the present invention in some embodiments thereof, relates to compositions and, more particularly, but not exclusively, to personal care formulations with antimicrobial (also referred to as "anti-micro-organic") activity, articles containing same, and uses thereof in, for example, reducing or preventing growth of microorganisms.
  • antimicrobial also referred to as "anti-micro-organic”
  • High quality antimicrobial formulations are desirable as they provide a good solution to biofouling and/or infection processes and/or formation of biofilms on a surface.
  • Conventional personal care formulations present several drawbacks, as many of these formulations are referred to as being toxic (or releasing toxic materials to the environment), instable, inefficient or are limited in preventing (or complete diminishing) microorganism growth, expensive and produced via complicated manufacturing processes which at times require expensive equipment for their manufacture.
  • non-toxic antimicrobial formulations also referred to as "blends" comprising active compounds of natural extracts e.g., thymol, and linalool, as well as phenoxyethanol or phenyl ethyl alcohol in a weight ratio of 9: 1 to 5:5, respectively, for use as e.g., cosmetic composition and for various articles.
  • non-limiting examples of such uses can include personal hygiene and treatment of specific skin regions-of-interest.
  • the disclosed formulations are both efficient, cost-effective antimicrobial formulations.
  • linalool refers to (R)-(-)-linalool (also known as licareol).
  • “linalool” refers to (S)-(+)-linalool (also known as coriandrol). In some embodiments, “linalool” refers to a mixture of licareol and coriandrol.
  • compositions e.g., formulations
  • a solvent e.g., propylene glycol (designated as PG) or phenyl ethyl alcohol
  • compositions comprising thymol and phenoxyethanol, or phenyl ethyl alcohol being at certain predetermined ratios
  • exhibit a desired stability as well as improved antimicrobial activities compared to other compositions comprising different materials from the invented formulations or from formulations comprising the same materials but having different volume or weight ratios thereof.
  • the desired solvents are selected from the group consisting of: phenoxyethanol, benzyl alcohol, and phenyl ethanol or a combination thereof.
  • the solvents are devoid of 1 ,2-propylene glycol and/or hexylene glycol.
  • the present inventors have shown that a specific ratio of thymol/linalool exhibits both synergistic antimicrobial effect and further an effective odor control benefit, i.e. masking the odor of thymol.
  • a specific ratio of thymol/ phenoxyethanol, or phenyl ethyl alcohol with the addition of odor masking agents exhibits similar effects.
  • the odor masking agent are selected from: liffarome, capric acid, or a combination thereof.
  • “liffarome” refers to cis-hex-3-enyl methyl carbonate. In some embodiments, “liffarome” refers to the chemical with CAS no. 67633-96-9. In some embodiments, “liffarome” refers to liffarome and any derivatives thereof. In some embodiments, liffarome further refers to any enantiomer, diastereomer, solvate or hydrate of liffarome.
  • capric acid refers to decanoic acid. In some embodiments, “capric acid” refers to the chemical with CAS no. 334-48-5. In some embodiments, “capric acid” refers to capric acid and any derivatives thereof. In some embodiments, capric acid further refers to any enantiomer, diastereomer, solvate or hydrate of capric acid.
  • the compounds described herein above possess asymmetric carbon atoms (optical centers) or double bonds; the racemates, diastereomers, geometric isomers and individual isomers are encompassed within the scope of the present invention.
  • the term “enantiomer” describes a stereoisomer of a compound that is superposable with respect to its counterpart only by a complete inversion/reflection (mirror image) of each other. Enantiomers are said to have "handedness” since they refer to each other like the right and left hand. Enantiomers have identical chemical and physical properties except when present in an environment which by itself has handedness, such as all living systems.
  • the compounds hereabove described can exist in unsolvated forms as well as solvated forms, including hydrated forms.
  • the solvated forms are equivalent to unsolvated forms and are encompassed within the scope of the present invention.
  • solvate refers to a complex of variable stoichiometry (e.g., di-, tri-, tetra-, penta-, hexa-, and so on), which is formed by a solute (the conjugate described herein) and a solvent, whereby the solvent does not interfere with the biological activity of the solute.
  • Suitable solvents include, for example, ethanol, acetic acid and the like.
  • hydrate refers to a solvate, as defined hereinabove, where the solvent is water.
  • present inventors have also shown that the disclosed formulation can be used to impart to articles the antimicrobial activities.
  • the composition is in the form of a formulation.
  • the composition is a stable preservative.
  • the stable personal care formulation comprises: thymol (also known as 2-isopropyl-5-methylphenol), an organic solvent and Hnalool (also known as 3,7-dimethylocta-l,6-dien-3-ol).
  • thymol and Hnalool are at a ratio of e.g., about 9: 1, about 8:2, about 7:3, about 7:2, 6:4, 5:5, respectively, by weight, including any value and range therebetween.
  • the stable personal care formulation comprises: thymol and phenoxyethanol (also known as l-hydroxy-2-phenoxyethane).
  • the thymol and phenoxyethanol are at a ratio of e.g., about 9: 1, about 8:2, about 7:3, about 7:2, 6:4, 5:5, respectively, by weight, including any value and range therebetween.
  • the stable personal care formulation comprises: thymol and phenyl ethyl alcohol (also known as 2-phenylethanol).
  • the thymol and phenyl ethyl alcohol are at a ratio of e.g., about 9: 1, about 8:2, about 7:3, about 7:2, 6:4, 5:5, respectively, by weight, including any value and range therebetween.
  • the formulation is a personal care formulation.
  • the formulation comprises thymol at a concentration of e.g., about 5%, about 10%, about 15%, about 20%, about 25%, about 30%, about 35%, about 40%, by weight, including any value and range therebetween.
  • the formulation comprises Hnalool at a concentration of e.g., about 3%, about 5%, about 10%, about 15%, about 20%, about 25%, about 30%, about 35%, by weight, including any value and range therebetween.
  • the formulation comprises phenoxyethanol at a concentration of e.g., about 50%, about 55%, about 60%, about 65%, about 70%, about 75%, about 80%, about 85%, by weight, about 90%, by weight, including any value and range therebetween.
  • the formulation comprises phenyl ethyl alcohol at a concentration of e.g., about 50%, about 55%, about 60%, about 65%, about 70%, about 75%, about 80%, about 85%, by weight, about 90%, by weight, including any value and range therebetween.
  • the formulation further comprises a solvent.
  • the formulation comprises 65% solvent (by weight) and further comprises:
  • the solvent comprises 0-10% water.
  • the organic solvent comprises diol or triol.
  • the glycol is selected from the group consisting of ethylene glycol, diethylene glycol, triethylene glycol, tetraethylene glycol, pentylene glycol and hexylene glycol.
  • the organic solvent comprises benzyl alcohol, phenoxyethanol, phenyl ethyl alcohol, 3-phenyl propanol, substituted or non-substituted, or a combination thereof.
  • the formulation further comprises an odor masking agent.
  • the odor masking agent is liffarome.
  • the odor masking agent is capric acid.
  • the odor masking agent is a combination of liffarome and capric acid.
  • the formulation comprises 0.12% liffarome (by weight) and further comprises:
  • the formulation comprises 0.12% liffarome (by weight) and 1.5% capric acid (by weight) and further comprises:
  • liffarome is at a concentration of e.g., about 0.05 %, 0.12 %, 0.22 %, 0.32 %, 0.42 %, 0.52 %, 0.62 %, 0.72 %, 0.82 %, 0.92 %, 1 %, 2 %, 3 %, 4 %, 5 %, 6 %, 7 %, 8 %, 9 %, or 10 %, by weight, including any value and range therebetween.
  • capric acid is at a concentration of e.g., about 0.05 %, 0.1 %, 0.5 %, 1 %, 2 %, 3 %, 4 %, 5 %, 6 %, 7 %, 8 %, 9 %, 10 %, 15 %, or 20 %, by weight, including any value and range therebetween.
  • the formulation of the invention may include an emulsifier.
  • emulsifier is intended to mean a surface-active agent that facilitates the mixing of two or more liquid substances that would separate into its component parts under normal conditions.
  • Surface- active agents may include surfactants, which typically provide detersive functionality to a formulation or act simply as wetting agents.
  • Surface-active agents may generally be categorized as anionic surface-active agents, cationic surface-active agents, nonionic surface-active agents, amphoteric surface-active agents and zwitterionic surface-active agents, and dispersion polymers.
  • Exemplary emulsifiers include, but are not limited to, sodium lauroyl lactylate (SLL), Tween 20, PEG 40-hdrogenatedcster oil, cocoamide monoethanolamide (MEA), cocoamide diethanolamid (DEA), diacetyl tartaric acid ester of mono- and diglycerides (DATEM), potassium cocoate, and any combination thereof.
  • SLL sodium lauroyl lactylate
  • Tween 20 PEG 40-hdrogenatedcster oil
  • MEA cocoamide monoethanolamide
  • DEA cocoamide diethanolamid
  • DATEM diacetyl tartaric acid ester of mono- and diglycerides
  • potassium cocoate potassium cocoate
  • the emulsifier is at a concentration of e.g., about 0.05 %, 0.1 %, 0.2 %, 0.3 %, 0.4 %, 0.5 %, 0.6 %, 0.7 %, 0.8 %, 0.9 %, 1 %, 2 %, 3 %, 4 %, 5 %, 6 %, 7 %, 8 %, 9 %, 10 %, 15 %, or 20 %, by weight, including any value and range therebetween.
  • the formulation is devoid of paraben. In some embodiments, the formulation is devoid of formaldehyde. In some embodiments, the formulation is devoid of a compound comprising halogen. In some embodiments, the formulation is devoid of a compound comprising halogen and is further devoid of paraben. In some embodiments, the formulation is devoid of formaldehyde and is further devoid of paraben. In some embodiments, the formulation is devoid of a compound comprising halogen and is further devoid of paraben. In some embodiments, the formulation is devoid a compound comprising halogen and is further devoid of formaldehyde. In some embodiments, the formulation is devoid of paraben, formaldehyde and is further devoid of a compound comprising halogen
  • the formulation is not pH dependent.
  • the formulation is characterized by pH below 7. In some embodiments of the present invention, the formulation is characterized by pH below 6. In some embodiments of the present invention, the formulation is characterized by pH below 5. In some embodiments of the present invention, the formulation is characterized by pH below 4. In some embodiments of the present invention, the formulation is characterized by pH below 3.
  • the formulation is characterized by pH in the ranges of about 5 to about 7. In some embodiments of the present invention, the formulation is a part of a product, article or composition characterized by pH in the ranges of about 3 to about 9. In some embodiments of the present invention, the formulation further comprises a buffer solution or a pH adjuster to control the desired pH of the formulation.
  • formulation refers to a vehicle composition in the form of emulsion, lotion, cream, gel etc., that optionally further comprises physiologically acceptable carriers and/or excipients and optionally other chemical components such as cosmetically, cosmeceutically or pharmaceutically active agents (e.g., drugs).
  • the formulation can optionally further comprise a carrier, and optionally additional active agents and/or additives e.g., anti-freezing agents).
  • physiologically acceptable means approved by a regulatory agency of the Federal or a state government or listed in the U.S. Pharmacopeia or other generally recognized pharmacopeia for use in animals, and more particularly in humans.
  • excipient refers to an inert substance added to a formulation as described herein to further facilitate processes and administration of the active ingredients.
  • the formulation of the invention can be prepared by any commonly used method for preparing a composition of materials.
  • the components of the formulations may be added and mixed together, or one of the components may be added to the other in the form of a solution which may, if desired, be evaporated or lyophilized after mixing for obtaining a homogeneous and stable solution or suspension.
  • stable formulation or “long-lasting formulation” mean that the formulation remains in a state or condition of sufficient stability to have utility as a personal care agent, while maintaining the antimicrobial activity (with ⁇ 20% variation).
  • the formulation has a sufficient stability to allow storage at a convenient temperature, e.g., between 10 °C and 30 °C, for a reasonable period of time of e.g., longer than one month, longer than three months, longer than six months, and longer than one year.
  • consumer product forms include, but are not limited to, shampoos, aftershaves, sunscreens, body and hand lotions, skin creams, liquid soaps, bar soaps, bath oil bars, shaving creams, conditioners, permanent waves, hair relaxers, hair bleaches, hair detangling lotion, styling gel, styling glazes, spray foams, styling creams, styling waxes, styling lotions, mousses, spray gels, pomades, shower gels, bubble baths, hair coloring preparations, conditioners, hair lighteners, coloring and non- coloring hair rinses, hair grooming aids, hair tonics, spritzes, styling waxes, band-aids, and balms.
  • the disclosed formulation is in the form of, or a part of, a cream, an ointment, a paste, a gel, a lotion, a milk, an oil, a suspension, a solution, an aerosol, a spray, a foam, or a mousse.
  • Ointments are semisolid preparations, typically based on petrolatum or petroleum derivatives.
  • the specific ointment base to be used is one that provides for optimum delivery for the active agent chosen for a given formulation, and, preferably, provides for other desired characteristics as well (e.g., emolliency).
  • an ointment base should be inert, stable, nonirritating and nonsensitizing.
  • ointment bases may be grouped in four classes: oleaginous bases; emulsifiable bases; emulsion bases; and water-soluble bases.
  • Oleaginous ointment bases include, for example, vegetable oils, fats obtained from animals, and semisolid hydrocarbons obtained from petroleum.
  • Emulsifiable ointment bases also known as absorbent ointment bases, contain little or no water and include, for example, hydroxystearin sulfate, anhydrous lanolin and hydrophilic petrolatum.
  • Emulsion ointment bases are either water-in-oil (W/O) emulsions or oil-in-water (O/W) emulsions, and include, for example, cetyl alcohol, glyceryl monostearate, lanolin and stearic acid.
  • Exemplary water-soluble ointment bases are prepared from polyethylene glycols of varying molecular weight.
  • Lotions are preparations that are to be applied to the skin surface without friction.
  • Lotions are typically liquid or semiliquid preparations in which solid particles, including the sunscreens- containing microcapsules, are present in a water or alcohol base.
  • Lotions are typically preferred for covering/protecting large body areas, due to the ease of applying a more fluid composition.
  • Lotions are typically suspensions of solids, and oftentimes comprise a liquid oily emulsion of the oil-in-water type. It is generally necessary that the insoluble matter in a lotion be finely divided.
  • Lotions typically contain suspending agents to produce better dispersions as well as compounds useful for localizing and holding the active agent in contact with the skin, such as methylcellulose, sodium carboxymethyl- cellulose, and the like.
  • Creams are viscous liquids or semisolid emulsions, either O/W or W/O.
  • Cream bases are typically water- washable, and contain an oil phase, an emulsifier and an aqueous phase.
  • the oil phase also called the "internal” phase, generally comprises petrolatum and/or a fatty alcohol such as cetyl or stearyl alcohol.
  • the aqueous phase typically, although not necessarily, exceeds the oil phase in volume, and generally contains a humectant.
  • the emulsifier in a cream formulation is generally a nonionic, anionic, cationic or amphoteric surfactant. Reference may be made to Remington: The Science and Practice of Pharmacy, supra, for further information.
  • Pastes are semisolid dosage forms in which the bioactive agent is suspended in a suitable base. Depending on the nature of the base, pastes are divided between fatty pastes or those made from a single-phase aqueous gel.
  • the base in a fatty paste is generally petrolatum, hydrophilic petrolatum and the like.
  • the pastes made from single-phase aqueous gels generally incorporate carboxymethylcellulose or the like as a base. Additional reference may be made to Remington: The Science and Practice of Pharmacy, for further information.
  • Gel formulations are semisolid, suspension-type systems.
  • Single-phase gels contain organic macromolecules distributed substantially uniformly throughout the carrier liquid, which is typically aqueous, but also, preferably, contain an alcohol and, optionally, an oil.
  • Preferred organic macromolecules, i.e. gelling agents are crosslinked acrylic acid polymers such as the family of carbomer polymers, e.g., carboxypolyalkylenes that may be obtained commercially under the trademark CarbopolTM.
  • hydrophilic polymers such as polyethylene oxides, polyoxyethylene-polyoxypropylene copolymers and polyvinylalcohol
  • cellulosic polymers such as hydroxypropyl cellulose, hydroxyethyl cellulose, hydroxypropyl methylcellulose, hydroxypropyl methylcellulose phthalate, and methyl cellulose
  • gums such as tragacanth and xanthan gum
  • sodium alginate and gelatin.
  • dispersing agents such as alcohol or glycerin can be added, or the gelling agent can be dispersed by trituration, mechanical mixing or stirring, or combinations thereof.
  • Sprays generally provide the active agent in an aqueous and/or alcoholic solution which can be misted onto the skin for delivery.
  • Such sprays include those formulated to provide for concentration of the active agent solution at the site of administration following delivery, e.g., the spray solution can be primarily composed of alcohol or other like volatile liquid in which the active agent can be dissolved.
  • the carrier evaporates, leaving concentrated active agent at the site of administration.
  • Foam compositions are typically formulated in a single or multiple phase liquid form and housed in a suitable container, optionally together with a propellant which facilitates the expulsion of the composition from the container, thus transforming it into a foam upon application.
  • Other foam forming techniques include, for example the "Bag-in-a-can" formulation technique.
  • Compositions thus formulated typically contain a low-boiling hydrocarbon, e.g., isopropane. Application and agitation of such a composition at the body temperature cause the isopropane to vaporize and generate the foam, in a manner similar to a pressurized aerosol foaming system.
  • Foams can be water-based or hydroalcoholic, but are typically formulated with high alcohol content which, upon application to the skin of a user, quickly evaporates, driving the active ingredient through the upper skin layers to the site of treatment.
  • Personal care formulations can further include, without limitation, human body or hair deodorizing solution, deodorizing gel, deodorizing spray, deodorizing stick, deodorizing roll-on, deodorizing paste, deodorizing cream, deodorizing lotion, deodorizing aerosol, and other commonly marketed human body and commonly marketed animal and pet deodorizing compositions.
  • Additional cosmetically or pharmaceutically beneficial (active) ingredients can also be included in the formulations of the present invention, which can be selected from, but are not limited to, skin cleansers, cationic, anionic surfactants, non-ionic surfactants, amphoteric surfactants, and zwitterionic surfactants, skin and hair conditioning agents, vitamins, hormones, minerals, plant extracts, anti-inflammatory agents, collagen and elastin synthesis boosters, UVA/UVB sunscreens, concentrates of plant extracts, emollients, moisturizers, skin protectants, humectants, silicones, skin soothing ingredients, antimicrobial agents, antifungal agents, treatment of skin infections and lesions, blood microcirculation improvement, skin redness reduction benefits, additional moisture absorbents, analgesics, skin penetration enhancers, solubilizers, moisturizers, emollients, anesthetics, colorants, perfumes, preservatives, seeds, broken seed nut shells, silica, clays, beads,
  • the formulation is characterized by resistance to discoloration.
  • coloration is defined as change in the hue or in the visual appearance of a formulation, due to an internal reaction among its constituents or the bleaching or oxidation action caused by a combination of factors that include, but are not limited to, air, high temperature, humidity, ultraviolet exposure e.g., sunlight.
  • an article which comprises any one of the personal care formulation described herein.
  • a pharmaceutical, cosmetic or cosmeceutical product comprising the formulation described in any of their respective embodiments herein, for use in treating a medical, cosmetic or cosmeceutic condition, as described herein.
  • the formulation described in any of their respective embodiments herein is used as, or a part of, a preservative in any pharmaceutical, cosmetic or cosmeceutical product or in any article as describe herein.
  • preservative is used to prevent the growth of bacteria, fungi and/or molds in any personal care composition or formulation.
  • a use of the formulation described herein in the manufacture of a pharmaceutical, cosmetic or cosmeceutical product which can be used in treating a medical, cosmetic or cosmeceutic condition, as described herein.
  • a method of treating a medical, cosmeceutical or cosmetic condition treatable by a topical or transdermal administration comprising topically applying the formulation described herein (e.g., in the context of a pharmaceutical, cosmetic or cosmeceutic product) to a skin or mucosal tissue of a subject afflicted by the condition.
  • topical topical administrations
  • applications which include, without limitation, dermal applications, ophthalmic application, vaginal application, rectal application and intranasal application.
  • Medical, cosmetic or cosmeceutical conditions that can benefit from containing the formulations described herein when applied topically, with or without an additional active ingredient, include, but are not limited to, infections caused by pathogenic microorganisms, as discussed in further detail hereinbelow, wounds, particularly when associated with an infection, acne, skin infections, viral blisters such as one caused by herpes, sexual dysfunction such as erectile dysfunction.
  • the pharmaceutical, cosmetic or cosmeceutical formulation or product further comprises an antimicrobial agent, as an additional pharmaceutically active agent.
  • Microbial infections include any infection caused by a pathogenic microorganism, including, bacterial infection, fungal infection, protozoal infection, viral infection and the like, e.g., molluscum contagiosum (a viral infection of the skin or occasionally of the mucous membranes), fungal nail infections, and cutaneous leishmaniasis.
  • a pathogenic microorganism including, bacterial infection, fungal infection, protozoal infection, viral infection and the like, e.g., molluscum contagiosum (a viral infection of the skin or occasionally of the mucous membranes), fungal nail infections, and cutaneous leishmaniasis.
  • Topical bodily sites include skin, mucosal tissue, eye, ear, nose, mouth, rectum and vagina.
  • an article e.g., a medical device such as a bandage or adhesive patch
  • a formulation or a product, as described herein, configured for topical application, whereby a condition treatable by such as article, product or formulation is an infection caused by a microorganism.
  • the article is e.g., a fabric, a bandage, a wipe (e.g., a wet wipe), a pledget, a swab, a suppository, a dressing, a solution, a mousse, a pad, or a patch.
  • the article is in the form of paste, cream, lotion, foam, gel, emulsion, an ointment, or soap.
  • the personal care formulation of the present invention can be used to treat skin tissue or on damaged or unhealthy skin tissue.
  • damaged or unhealthy skin tissue refers to a deviation from healthy functional skin tissue.
  • skin a skin that is weaker, less elastic, and is more prone to injury than healthy skin.
  • the structure of unhealthy or damaged skin is inferior to that of healthy skin (for example, the dermis and epidermis contain fewer cells and collagen).
  • healthy skin tissue refers to skin that is strong, elastic, smooth and plump.
  • One purpose of treating healthy skin is to prevent deterioration of skin induced by aging or environmental stress including, but not limited to, microbial infection.
  • damaged refers broadly to injuries to the skin and subcutaneous tissue as well as internal organs initiated in any one of a variety of ways (e.g., pressure sores from extended bed rest, wounds induced by trauma, wounds received during or following a surgical procedure and the like) and with varying characteristics.
  • Examples include, but are not limited to, bruises, scrapes, burn wounds, sunburn wounds, incisional wounds, excisional wounds, surgical wounds, necrotizing fascitis, ulcers, venous stasis ulcers, diabetic ulcers, decubitus ulcers, aphthous ulcers, pressure ulcers, scars, alopecia areata, dermatitis, allergic contact dermatitis, atopic dermatitis, berloque dermatitis, diaper dermatitis, dyshidrotic dermatitis, psoriasis, eczema, erythema, warts, anal warts, angioma, cherry angioma, athlete's foot, atypical moles, basal cell carcinoma, Bateman's purpura, bullous pemphigoid, Candida, chondrodermatitis helicis, Clark's nevus, cold sores, condylomata, cysts, Darier
  • a method of inhibiting or reducing or retarding the formation of load of a microorganism and/or the formation of a biofilm, in and/or on an article comprises incorporating in and/or on the article any one of the formulations disclosed herein, including any of the respective embodiments thereof.
  • the article can be any one of the articles described herein.
  • Such articles take advantage of the improved antimicrobial activity exhibited by the formulations as described herein.
  • thymol, linalool, phenoxyethanol and phenyl ethyl alcohol can be used effectively in antimicrobial compositions, and when used in various combinations with each other at define weight ratio (e.g., from about 90: 10 to about 70:30 thymol/linalool, phenoxyethanol, or phenyl ethyl alcohol), these compounds show synergistic activity effect.
  • synergism or any grammatical derivative thereof, is defined as the simultaneous action of two or more compounds in which the total response of an organism to the combination is greater than the sum of the individual components.
  • antimicrobial activity is referred to as an ability to inhibit (prevent), reduce or retard bacterial growth, fungal growth, biofilm formation or eradicate living bacterial cells, or their spores, or fungal cells or viruses in a suspension or in a moist environment.
  • inhibiting or reducing or retarding the formation of load of a microorganism refers to inhibiting, reducing, or retarding growth of microorganisms and/or eradicating a portion or all of an existing population of microorganisms.
  • formulations described herein can be used both in reducing the formation of microorganisms on or in an article, and in killing microorganisms in or on an article or a living tissue.
  • the microorganism can be, for example, a unicellular microorganism (prokaryotes, archaea, bacteria, eukaryotes, protists, fungi, algae, molds, yeast, euglena, protozoan, dinoflagellates, apicomplexa, trypanosomes, amoebae and the likes), or a multicellular microorganism.
  • a unicellular microorganism prokaryotes, archaea, bacteria, eukaryotes, protists, fungi, algae, molds, yeast, euglena, protozoan, dinoflagellates, apicomplexa, trypanosomes, amoebae and the likes
  • a multicellular microorganism multicellular microorganism
  • An article, according to these embodiments, can be also a living tissue, for example, a skin or mucosal tissue, as described herein.
  • the formulations, articles and methods described herein may be used to produce cell inhibiting surface, or a microbial cell killing surface, that remains active for extended periods.
  • Such an antimicrobial surface may not need additional treatment with antimicrobial compositions, clean-up treatments to effect decontamination and cosmetic painting, thereby simplifying upkeep of the physical condition and appearance of microbial infestation prone surfaces.
  • the formulations of the present invention may be easily applied to susceptible surfaces in advance of and/or during exposure to a microbial organism.
  • the microorganism comprises bacterial cells of bacteria such as, for example, Gram-positive and Gram-negative bacteria.
  • the Gram-positive bacteria are Staphylococcus aureus, Staphylococcus epidermidis, and Bacillus cereus.
  • the Gram-negative bacteria are Escherichia coli, Pseudomonas aeuruginosa, and Burkholderia cepacia.
  • the microorganism is fungi e.g., Candida albicans and Aspergillus niger.
  • biofilm refers to an aggregate of living cells which are stuck to each other and/or immobilized onto a surface as colonies.
  • the cells are frequently embedded within a self-secreted matrix of extracellular polymeric substance (EPS), also referred to as “slime”, which is a polymeric sticky mixture of nucleic acids, proteins and polysaccharides.
  • EPS extracellular polymeric substance
  • the living cells forming a biofilm can be cells of a unicellular microorganism (prokaryotes, archaea, bacteria, eukaryotes, protists, fungi, algae, euglena, protozoan, dinoflagellates, apicomplexa, trypanosomes, amoebae and the likes), or cells of multicellular organisms in which case the biofilm can be regarded as a colony of cells (like in the case of the unicellular organisms) or as a lower form of a tissue.
  • a unicellular microorganism prokaryotes, archaea, bacteria, eukaryotes, protists, fungi, algae, euglena, protozoan, dinoflagellates, apicomplexa, trypanosomes, amoebae and the likes
  • the biofilm can be regarded as a colony of cells (like in the case of the unicellular organisms)
  • the cells are of microorganism origins, and the biofilm is a biofilm of microorganisms, such as bacteria and fungi.
  • the cells of a microorganism growing in a biofilm are physiologically distinct from cells in the "planktonic form" of the same organism, which by contrast, are single-cells that may float or swim in a liquid medium.
  • Biofilms can go through several life-cycle steps which include initial attachment, irreversible attachment, one or more maturation stages, and dispersion.
  • antibiofilm formation activity refers to the capacity of a substance to affect the prevention of formation of a biofilm of bacterial, fungal and/or other cells, and/or to affect a reduction in the rate of buildup of a biofilm of bacterial, fungal and/or other cells, on a surface of a substrate. This activity is also referred to herein as anti-biofouling activity, or antifouling activity.
  • preventing in the context of antimicrobial, indicates that the growth rate of the microorganism cells is essentially nullified or is reduced by at least 20 %, at least 30 %, at least 40 %, at least 50 %, at least 60 %, at least 70 %, at least 80 %, at least 90 %, including any value therebetween, of the appearance of the microorganism in a comparable situation lacking the presence of formulation or an article containing same.
  • preventing means a reduction to at least 15 %, 10 % or 5 % of the appearance of the microorganism cells in a comparable situation lacking the presence of the formulation or an article containing same.
  • the anti-odor components attempt to absorb or merely mask the odor.
  • the anti-odor components may act on the underlying bacterial organisms.
  • the linalool masks the thymol's odor, that is, further acts as a smell masking agent.
  • liffarome masks the thymol's odor.
  • liffarome and capric acid mask the thymol's odor.
  • Smell tests may be used to analyze the effectiveness of a masking agent. For example, a panel of people comprising a significant number and cross-section of people blindly smells the formulation comprising the thymol and/or the masking agent. The results may be statistically analyzed using parametric or non-parametric methods. In order to eliminate the influence of the difference among individual panelists and their physical conditions, in vitro and automated systems are also available to measure smell. Such systems are available from companies such as Odotech Inc.
  • compositions, methods or structure may include additional ingredients, steps and/or parts, but only if the additional ingredients, steps and/or parts do not materially alter the basic and novel characteristics of the claimed formulation, method or structure.
  • a compound or “at least one compound” may include a plurality of compounds, including mixtures thereof.
  • a range should be considered to have specifically disclosed all the possible subranges as well as individual numerical values within that range.
  • description of a range such as from 1 to 6 should be considered to have specifically disclosed subranges such as from 1 to 3, from 1 to 4, from 1 to 5, from 2 to 4, from 2 to 6, from 3 to 6 etc., as well as individual numbers within that range, for example, 1, 2, 3, 4, 5, and 6. This applies regardless of the breadth of the range.
  • method refers to manners, means, techniques and procedures for accomplishing a given task including, but not limited to, those manners, means, techniques and procedures either known to, or readily developed from known manners, means, techniques and procedures by practitioners of the chemical, pharmacological, biological, biochemical and medical arts.
  • treating includes abrogating, substantially inhibiting, slowing or reversing the progression of a condition, substantially ameliorating clinical or aesthetical symptoms of a condition or substantially preventing the appearance of clinical or aesthetical symptoms of a condition.
  • the minimum inhibitory concentration (MIC) was determined by applying the broth microdilution method and monitoring the bacterial growth using absorbance measurement at 600 nm. The test is performed in ELISA microplates for bacterial strains and Candida albicans. Microbial growth was estimated by reading O.D at 600 nm.
  • a pure culture of a single microorganism was grown in Tryptic soy broth, or sabouraud broth for yeast and mold.
  • the culture is standardized using standard microbiological techniques to have a concentration of very near 1 million cells per milliliter.
  • the antimicrobial agent is diluted a number of times, with Tryptic soy broth or sabouraud broth for fungi. After the antimicrobial agent had been diluted, a volume of the standardized inoculums was added to each dilution vessel, bringing the microbial concentration to approximately 500,000 cells per milliliter.
  • the inoculated, serially diluted antimicrobial agent was incubated at an appropriate temperature for the test organism, 24 hours for bacteria 48 for yeast and 72 for mold.
  • the series of dilution vessels was observed for microbial growth, usually indicated by turbidity and/or a pellet of microorganisms in the bottom of the vessel.
  • the last tube in the dilution series that does not demonstrate growth corresponds with the minimum inhibitory concentration (MIC) of the antimicrobial agent.
  • the antimicrobial preservative effectiveness was tested to measure the efficiency of a preservative.
  • the method applied is based on the USP 30 guidelines for antimicrobial effectiveness testing.
  • the microorganisms used for the test were E. coli ATCC 8739, P.aeruginosa ATCC 9027 , S. aureus ATCC 6538, C. albicans ATCC 10231, A. niger ATCC 16404.
  • CFU colony forming unit
  • Thymol, cinnamaldehyde and Eugenol are known to have antimicrobial activity. They are active compounds of natural extracts. The results below (Table 1) demonstrate that it is possible to mimic a natural extract for preservation.
  • Thymol has a significant odor, and therefore smell masking agent was called for.
  • three smell masking agents were examined: vanillin, linalool and menthol. The antimicrobial activity of these agents was tested as shown in Table 2.
  • linalool exhibits the best antimicrobial activity. Menthol is a crystalline substance with low solubility and does not have significant antimicrobial activity. Vanillin is less chemically stable. Therefore, linalool was chosen as a smell masking agent for the blends due to his antimicrobial activity and pleasant smell in combination with thymol.
  • Thymol is in the form of a powder and it cannot be easily combined with linalool without a solvent. Therefore, in exemplary procedures, blends with propylene glycol as a solvent were prepared. Different ratios of thymol /linalool were tested in order to find the most effective ratio.
  • blends with thymol /linalool ratio 70:30, 80:20, 90: 10 provide the best antimicrobial activity.
  • the antimicrobial preservative effectiveness was tested to measure the efficiency of a preservative.
  • the sample tested was a face cream.
  • the Preservation tested was: 1.4% (thymol: 24.5% + linalool: 10.5% + propylene glycol: 65%) pH: 6.6.
  • Method applied The method applied is based on the USP 30 guidelines for antimicrobial effectiveness testing.
  • the microorganisms used for the test are listed in the Table 4 below. Five samples of the product are inoculated with one microorganism each. The volume of the culture is calculated to yield a count of 10 5 - 10 6 CFU/gr.
  • Linalool as a single
  • blends with benzyl alcohol, phenyl ethyl alcohol and phenoxyethanol as solvents have better microbiological activity than blends with Propylene glycol. It can also be concluded that blend with phenyl ethyl alcohol has a better activity than blends with phenoxyethanol and benzyl alcohol.
  • PRESERVATIVE EFFECTIVENESS CHALLENGE TESTS
  • the sample tested was a face cream.
  • the preservation composition was:
  • the sample tested was a face cream and the preservation composition was:
  • the sample tested was a face cream and the preservation composition was:
  • Thymol has a significant odor, and therefore requires a smell masking agent.
  • Fifteen smell masking agents were tested to enhance the odor of the thymol, linalool and phenoxyethanol composition.
  • Liffarome, 4-carvomenthenol, carvacrol, benzoic acid, sorbic acid, citric acid, capric acid, lactic acid, palmitic acid, sebacic acid, myristic acid, undecylenic acid, citronellic acid, linalyl acetate, and alpha-bisabolol were all found to be ineffective in masking the odor that was still present in the Thymol: 24.5%
  • Linalool 10.5%
  • Phenoxyethanol 65% composition (Table 11, ++ :good masking, + :low masking, 0 :poor masking, - :no masking). Table 11
  • Capric acid 400 800 1800 300 400
  • Hffarome was successful in masking the thymol odor of a composition that lacked linalool (Table 13, ++ :good masking, + :low masking, 0 :poor masking, - :no masking), and did not reduce the antimicrobial efficacy of the compound (Table 12).
  • Liffarome was effective as only 0.12% of the composition by weight, and capric acid was effective as only 1.5% by weight.
  • the three new blends had the following compositions: Thymol: 24.5% + Phenoxyethanol:75.38% + liffarome: 0.12%; Thymol: 24.5% + Phenoxyethanol:73.88% + liffarome: 0.12% + capric acid 1.5%; and Thymol: 24.5% + Phenyl ethyl alcohol :75.38% + liffarome: 0.12%.
  • the antimicrobial preservative effectiveness was tested to measure the efficiency of a preservative.
  • the sample tested was a face cream.
  • the microorganisms used for the test are listed in the table below. Five samples of the product were inoculated with 1 microorganism each. The volume of the culture was calculated to yield a count of 10 5 - 10 6 CFU/gr. A 4 weeks follow-up is performed. Each product was sampled once a week and a viable count was performed. Polysorbate 20 and Soy Lecithin were added to the culture media in order to neutralize the preservatives and to enable the recovery of all living microorganisms .
  • the preservation composition was:
  • the sample tested was a face cream and the preservation composition was:

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Abstract

L'invention concerne une composition comprenant du thymol, un solvant organique et un agent masquant les odeurs choisi dans le groupe constitué du linalol et du liffarome, dans laquelle le thymol et le solvant organique sont présents dans des proportions variant de 1/1 à 15/85, en poids, respectivement ; et le thymol et l'agent masquant les odeurs sont présents dans des proportions variant de 100/0,1 à 1/1, en poids, respectivement. L'invention concerne en outre des articles comprenant cette composition.
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Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0950399A2 (fr) * 1998-02-23 1999-10-20 Takasago Institute For Interdisciplinary Science Inc. Compositions parfumantes à activité antimicrobienne
US20040242452A1 (en) * 2001-08-08 2004-12-02 Ken Shoji Perfume composition
WO2011017367A2 (fr) * 2009-08-06 2011-02-10 Anitox Corporation Conservateur pour l'eau et les aliments pour animaux

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0950399A2 (fr) * 1998-02-23 1999-10-20 Takasago Institute For Interdisciplinary Science Inc. Compositions parfumantes à activité antimicrobienne
US20040242452A1 (en) * 2001-08-08 2004-12-02 Ken Shoji Perfume composition
WO2011017367A2 (fr) * 2009-08-06 2011-02-10 Anitox Corporation Conservateur pour l'eau et les aliments pour animaux

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
FELIX ITEN ET AL.: "Additive Antimicrobial Effects of the Active Components of the Essential Oil of Thymus vulgaris -Chemotype Carvacrol", PLANTA MED, vol. 75, 3 April 2009 (2009-04-03), pages 1231 - 1236 *

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