WO2016084078A1 - Antimicrobial preservative compositions - Google Patents

Antimicrobial preservative compositions Download PDF

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Publication number
WO2016084078A1
WO2016084078A1 PCT/IL2015/051141 IL2015051141W WO2016084078A1 WO 2016084078 A1 WO2016084078 A1 WO 2016084078A1 IL 2015051141 W IL2015051141 W IL 2015051141W WO 2016084078 A1 WO2016084078 A1 WO 2016084078A1
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WO
WIPO (PCT)
Prior art keywords
personal care
acid
care formulation
formulation
concentration
Prior art date
Application number
PCT/IL2015/051141
Other languages
French (fr)
Inventor
Aaron Garzon
Ariel GLIKSBERG
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Sharon Laboratories Ltd.
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Filing date
Publication date
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Publication of WO2016084078A1 publication Critical patent/WO2016084078A1/en

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Classifications

    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00Cosmetics or similar toiletry preparations
    • A61K8/18Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/33Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing oxygen
    • A61K8/34Alcohols
    • AHUMAN NECESSITIES
    • A01AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01NPRESERVATION 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
    • A01N31/00Biocides, pest repellants or attractants, or plant growth regulators containing organic oxygen or sulfur compounds
    • A01N31/04Oxygen or sulfur attached to an aliphatic side-chain of a carbocyclic ring system
    • AHUMAN NECESSITIES
    • A01AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01NPRESERVATION 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
    • A01N37/00Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom having three bonds to hetero atoms with at the most two bonds to halogen, e.g. carboxylic acids
    • A01N37/10Aromatic or araliphatic carboxylic acids, or thio analogues thereof; Derivatives thereof
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00Cosmetics or similar toiletry preparations
    • A61K8/02Cosmetics or similar toiletry preparations characterised by special physical form
    • A61K8/0208Tissues; Wipes; Patches
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00Cosmetics or similar toiletry preparations
    • A61K8/18Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/33Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing oxygen
    • A61K8/34Alcohols
    • A61K8/345Alcohols containing more than one hydroxy group
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00Cosmetics or similar toiletry preparations
    • A61K8/18Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/33Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing oxygen
    • A61K8/36Carboxylic acids; Salts or anhydrides thereof
    • A61K8/368Carboxylic acids; Salts or anhydrides thereof with carboxyl groups directly bound to carbon atoms of aromatic rings
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00Cosmetics or similar toiletry preparations
    • A61K8/18Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/49Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds
    • A61K8/4973Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with oxygen as the only hetero atom
    • A61K8/498Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with oxygen as the only hetero atom having 6-membered rings or their condensed derivatives, e.g. coumarin
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61QSPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q17/00Barrier 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
    • A61Q17/005Antimicrobial preparations
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61QSPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q19/00Preparations for care of the skin

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, containing 3-phenylpropanol, processes of preparing same, 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.
  • R. M. E. Richards, and R. J. McBride. disclose the actions of benzalkonium chloride and chlorhexidine acetate in combination with benzyl alcohol, 2- phenylethanol, or 3-phenylpropanol, evaluated at subinhibitory concentrations by measuring the growth rates of Pseudomonas aeruginosa NCTC 6750 with phenylpropanol showing the greatest enhancement and benzyl alcohol showed the least enhancement.
  • WO2007/071089 discloses personal care products and compositions that comprise at least one preservative compound selected from the group consisting of phenoxyethanol, 2-phenyl ethanol, phenoxypropanol, 3-phenylpropanol and benzylalcohol, in a total concentration of 0.1 to 1% (w/w).
  • WO2006/081071 discloses a stable skin care composition comprising dehydroacetic acid and a dermatologically acceptable carrier comprising at least one oil.
  • U.S. Patent Application having Publication No. 2006/0093634 discloses a color stable personal care composition which includes one or more additional anti-microbial agents (e.g., preservatives) and other suitable antimicrobial agents which include sorbic acid, benzoic acid, and salts thereof, and mixtures thereof.
  • additional anti-microbial agents e.g., preservatives
  • suitable antimicrobial agents include sorbic acid, benzoic acid, and salts thereof, and mixtures thereof.
  • the present inventors have surprisingly uncovered that personal care formulations comprising up to 30% phenylpropanol, and more particularly, but not exclusively, 3-phenylpropanol, can be readily prepared, and that such formulations exhibit exceptional antimicrobial and anti-biofouling activity.
  • the present invention provides a personal care formulation comprising: 3-phenyl propanol in a concentration that ranges from 2% to 30% by volume; an organic acid selected from the group consisting of: dehydroacetic acid (DHA), benzoic acid, and a combination thereof; a diol and/or triol, the diol being selected from the group consisting of: 1,2-diol, 1,3-diol, and any combination thereof; and an emulsifier and/or alpha-dehydroxy acid.
  • DHA dehydroacetic acid
  • benzoic acid benzoic acid
  • the personal care formulation comprises a combination of DHA and benzoic acid.
  • the personal care formulation comprises 3-phenyl propanol at a concentration that ranges from 2% to 30% by volume; DHA at a concentration that ranges from 0.1% to 5% by volume, and benzoic acid at a concentration that ranges from about 0.1% to 7 % by volume, diol and/or triol at a concentration of up to 90 % by volume; and an one emulsifier and/or lactic acid at a concentration that ranges from 0.1% to 10 % by volume.
  • the 1,2 diol is propylene glycol.
  • the 1,3 diol is selected from the group consisting of: 1,3-butanediol, and 1,3-propandiol.
  • the triol is glycerol.
  • the emulsifier is selected from the group consisting of: 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, polyethoxylated fatty acids, polyethylene glycol glycerol fatty acid esters, alcohol-oil transesterification products, polyglycerized fatty acids, propylene glycol fatty acid esters, mono-and diglycerides, sterol and sterol derivatives, polyethylene glycol sorbitan fatty acid esters, polyethylene glycol alkyl ethers, sugar esters, polyethylene glycol alkyl phenols, polyoxyethylene-polyoxypropylene block copolymers, sorbitan fatty acid esters, low alcohol fatty acid esters, ionic sur
  • the alpha-dehydroxy acid is lactic acid and/or citric acid. According to one embodiment, the alpha-dehydroxy acid is citric acid. According to another embodiment, the alpha-dehydroxy acid is lactic acid. According to embodiments, the personal care formulation is characterized by resistance to discoloration in an atmospheric environment.
  • the personal care formulation further comprises citric acid at a concentration up to 2%, by volume.
  • the personal care formulation further comprises sorbic acid, at a concentration that ranges from about 1.5 % to about 5 % by volume.
  • the personal care formulation further comprises an aliphatic alcohol at a concentration that ranges from 1 % to 15 % by volume, with the aliphatic alcohol having at least 10 carbon atoms in its backbone chain.
  • the aliphatic alcohol is lauryl alcohol.
  • the present invention provides an article comprising the personal care formulation of the invention.
  • 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 selected from the group consisting of: paste, cream, lotion, foam, gel, emulsion, an ointment, and soap.
  • the personal care formulation is for pharmaceutical, cosmetic and/or cosmeceutical use.
  • 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 the article with the personal care formulation.
  • the microorganism is bacteria, fungi, or mold.
  • the bacteria are Gram positive bacteria selected from the group consisting of: Staphylococcus aureus, Staphylococcus epidermidis, and Bacillus cereus.
  • the bacteria are Gram negative bacteria selected from the group consisting of: Escherichia coli, Pseudomonas aeuruginosa, and Burkholderia cepacia.
  • said fungi are Candida albicans.
  • the molds are Aspergillus niger.
  • a process of preparing the personal care composition of the invention comprising subjecting a mixture of: 3-phenyl propanol; an organic acid selected from the group consisting of: (DHA) and benzoic acid, and any combination thereof; a diol and/or triol; and an emulsifier and/or lactic acid.
  • the present invention in some embodiments thereof, relates to personal care compositions and, more particularly, but not exclusively, to stable personal care formulations with antimicrobial (also referred to as "anti-micro-organic") activity, containing 2-30% 3-phenylpropanol, processes of preparing same, articles containing same, and uses thereof in, for example, reducing or preventing growth of microorganisms.
  • antimicrobial also referred to as "anti-micro-organic” activity
  • 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 3-phenyl propanol in concentration lower than 30 % for use as cosmetic composition and for various articles.
  • non-toxic antimicrobial formulations also referred to as "blends”
  • 3-phenyl propanol in concentration lower than 30 % for use as 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 e.g., formulations comprising 3-phenylpropanol
  • formulations comprising 3-phenyl propanol, at least one organic acid, diol or triol, and at least one emulsifier or lactic acid, all of which being at certain volumetric ratios, exhibit an improved stability as well as improved antimicrobial and/or antibiofilm activities, compared to other formations comprising different materials from the invented formulations or from formulations comprising the same materials but having different volumetric ratios thereof.
  • the present inventors have also shown that the disclosed formulation can be used to impart to articles the antimicrobial and/or antibiofilm activities.
  • a stable personal care composition In some embodiments the composition is a stable preservative. In some embodiments, the stable personal care formulation comprises: 3-phenyl propanol (also known as 3- phenyl 1- propanol) at a concentration of e.g., about 2%, about 5%, about 10%, about 15%, about 20%, about 25%, about 30%, about 35%, by volume, including any value therebetween.
  • 3-phenyl propanol also known as 3- phenyl 1- propanol
  • the personal care formulation further comprises phenethyl alcohol (also known as 2-phenylethanol) at a concentration of e.g., about 2%, about 5%, about 10%, about 15%, about 20%, about 25%, about 30%, about 35%, by volume, including any value therebetween.
  • the personal care formulation comprises: 1-phenyl 1-propanol at a concentration of e.g., about 2%, about 5%, about 10%, about 15%, about 20%, about 25%, about 30%, about 35%, by volume, including any value therebetween.
  • the personal care formulation comprises at least one organic acid. In some embodiments, the personal care formulation comprises a diol. In some embodiments, the personal care formulation comprises at least one emulsifier and/or alpha-dehydroxy acid. In some embodiments the alpha-dehydroxy acid is selected from the group consisting of: lactic acid and citric acid, and combination thereof. In some embodiments the alpha-dehydroxy acid is lactic acid. In some embodiments the alpha-dehydroxy acid is citric acid. In some embodiments the alpha- dehydroxy acid is a mixture of lactic acid and citric acid.
  • Non-limiting exemplary organic acids are: dehydroacetic acid (DHA), benzoic acid, and any combination thereof.
  • the personal care formulation comprises: benzoic acid, DHA, 3- Phenylpropanol, Propyleneglycol, Tween, Lactic acid, PEG-40 Hydrogenated castor oil, Lauryl alcohol, Sorbic acid, Citric acid, and SLL.
  • the benzoic acid is at a concentration of: e.g., 0%, 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, or 10%, including any value therebetween.
  • the DHA is at a concentration of e.g., 0.1%, 0.5%, 1%, 1.5%, 2%, 2.5%, 3%, 3.5%, 4%, 4.5%, or 5%, including any value therebetween.
  • the sorbic acid is at a concentration of e.g., 0%, 0.5%, 1%, 1.5%, 2%, 2.5%, 3%, 3.5%, or 4%, including any value therebetween.
  • the SLL is at a concentration of e.g., 0%, 0.5%, 1%, 1.5%, 2%, 2.5%, 3%, 3.5%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 11% or 12%, including any value therebetween, wherein, in some embodiments, any other emulsifier or lactic acid may be used.
  • the 3-Phenylpropanol is at a concentration of e.g., 1.5%, 2%, 4%, 6%, 8%, 10%, 12%, 14%, 16%, 18%, 20%, 22%, 24%, 26%, 28%, 30%, 32%, or 35%, including any value therebetween.
  • the propyleneglycol is at a concentration of e.g., 0%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 95%, 99%, including any value therebetween, wherein, in some embodiments, any other 1,2 or 1,3 diol may be used instead of propyleneglycol.
  • Tween 20 is at a concentration of e.g., 0%, 0.5%, 1%, 1.5%, 2%, 2.5%, 3%, 3.5%, 4%,5%, 6%, 7%, 8%, 9%, 10%, 11% or 12%, including any value therebetween.
  • the lactic acid is at a concentration of: e.g., 0%, 0.5%, 1%, 1.5%, 2%, 2.5%, 3%, 3.5%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 11% or 12%, including any value therebetween, wherein if the concentration of the emulsifier, e.g., SLL, is 0%, the lactic acid is at concentration higher than 0%.
  • the concentration of the emulsifier e.g., SLL
  • the lauryl alcohol is at a concentration of e.g., 0%, 0.5%, 1%, 1.5%, 2%, 2.5%, 3%, 3.5%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, or 20%, including any value therebetween.
  • the PEG-40 Hydrogenated castor oil is at a concentration of e.g., 0%, 0.5%, 1%, 1.5%, 2%, 2.5%, 3%, 3.5%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, or 15, including any value therebetween.
  • the citric acid is at a concentration of: e.g., 0%, 0.1%, 0.2%, 0.3%, 0.4%, 0.5%, 0.6%, 0.7%, 0.8%, 0.9%, 1%, 1.1%, 1.2%, 1.3%, 1.4%, or 1.5%, including any value therebetween.
  • the formulation is or comprises (percentages below refers to concentration, by volume; the percentage below may vary within ⁇ 5%): Benzoic acid- 5.5%; DHA- 2.5%; SLL -1%; 3-Phenylpropanol-17% and Propyleneglycol- 74%.
  • the formulation is or comprises: Benzoic acid- 5.5%; DHA -3%; SLL -3%; 3-Phenylpropanol-17%; and Propyleneglycol- 71.5%.
  • the formulation is or comprises: Benzoic acid- 5.5%; DHA -3%; Sorbic acid-2%; SLL -3%; 3-Phenylpropanol-17%; and Propyleneglycol- 69.5%.
  • the formulation is or comprises: Benzoic acid- 5.5%; DHA -3%; Sorbic acid- 2%; SLL -3%; Lauryl alcohol- 10%; 3- Phenylpropanol-17%; and Propylene glycol-59.5%.
  • the formulation is or comprises: Benzoic acid- 5.5%; DHA-3%; 3-Phenylpropanol- 17%; Lactic acid- 5%; and Propylene glycol- 69.5%.
  • the formulation is or comprises: Benzoic acid- 5.5%; DHA-3%; Sorbic acid-2%; 3-Phenylpropanol- 17%; Lactic acid- 5%; and Propylene glycol- 67.5%.
  • the formulation is comprises: Benzoic acid- 5.5%; DHA -3%; Sorbic acid-2%; SLL -3%; 3-Phenylpropanol- 17%; Propyleneglycol- 69.15%; and Anhydrous Citric acid-0.35%.
  • the formulation is or comprises: Benzoic acid- 5.5%; DHA -3%; Sorbic acid- 2%; Tween 20 -3%; Phenylpropanol-17%; and Propyleneglycol- 69.5%.
  • the formulation comprises a diol.
  • diol is intended to include any molecule having at least two hydroxyl groups.
  • diol does not exclude the possibility of additional hydroxyl groups also being present, and therefore specifically includes triols, polyols and the like.
  • diols of the present invention encompasses, but are not limited to, propane- 1,2- diol, propane- 1,3-diol, butane- 1 ,2-diol, butane- 1,3 -diol, butane- 1,4-diol, butane-2,3-diol, 2- methylpropane-1,2- diol, 2-methylpropane- 1,3-diol, 2-hydroxymethyl- 1 -propanol, pentane- 1 ,2-diol, pentane-2,3-diol, 2-hydroxymethyl-l-butanol, 2-methylbutane- 1 ,2-diol, 3- methylbutane- 1 ,2-diol, 2- methylbutane- 1,3 -diol, 3-methylbutane-l,3-diol, 2- methylbutane- 1,4-diol, and hexane- 1 ,2-di
  • the diol is 1,2- diol.
  • the 1,3- diol is 1,3-butanediol
  • the 1 ,2- diol is propane- 1 ,2-diol, also termed "propylene glycol”.
  • the diol is also a triol.
  • the triol is glycerol.
  • the diol is at a concentration of e.g., up to 5 %, 10 %, 20 %, 30 %, 40 %, 50 %, 60 %, 70 %, 80 %, 90 %, 95 %, or 99 %, by volume, including any value 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 SLL.
  • the personal care formulation comprises one or more organic acids.
  • the formulation comprises a lactic acid instead of one or more emulsifiers. In some embodiments of the present invention, the formulation comprises a lactic acid in addition to one or more emulsifiers.
  • the organic acids are selected from DHA and benzoic acid and any combination thereof.
  • the DHA 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 volume, including any value therebetween.
  • the benzoic acid 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 volume, including any value therebetween.
  • the formulation further comprises sorbic acid.
  • the sorbic acid is at a concentration of e.g., about 0.5 %, 1 %, 1.5 %, 2 %, 2.5 %, 3 %, 3.5 %, 4 %, 4.5%, 5 %, 5.5 %, 6 %, 6.5%, 7 %, 7.5 %, 8 %, 8.5 %, 9 %, or 10 %, by volume, including any value therebetween.
  • the formulation comprising sorbic acid further comprises ethylenediamine tetra acetate (EDTA).
  • EDTA ethylenediamine tetra acetate
  • the EDTA is at a concentration of e.g., about 0.005 %, about 0.006 %, about 0.007 %, about 0.008 %, about 0.009 %, about 0.01 %, about 0.02 %, about 0.03 %, about 0.04 %, about 0.05 %, about 0.06 %, about 0.07 %, about 0.08 %, about 0.09 %, about 0.1 %, about 0.15 %, or about 0.2 %, by volume, including any value therebetween.
  • the disclosed formulation is added to a face cream.
  • 0.1% EDTA is added to the face cream comprising any formulation of the present invention.
  • 0.1% EDTA is added to a formulation comprising Benzoic acid- 5.5%; DHA- 2.5%; SLL -1%; 3-Phenylpropanol-17%; and Propyleneglycol- 74%, by volume (percentage may vary between ⁇ 5%).
  • the formulation further comprises at least one type of long chain aliphatic alcohol.
  • long chain aliphatic alcohols are non-aromatic compounds which include, but are not limited to, alkanols that comprise at least 10 carbon atoms in its backbone chain and at least one hydroxyl group being bound thereto.
  • the long chain aliphatic alcohol is at a concentration of e.g., about 0.5 %, about 1 %, about 1.5 %, about 2 %, about 2.5 %, 3 about %, about 3.5 %, about 4 %, about 4.5%, about 5 %, about 5.5 %, about 6 %, about 6.5%, about 7 %, about 7.5 %, about 8 %, about 8.5 %, about 9 %, about 10 %, about 10.5 %, about 11 %, about 11.5 %, about 12 %, about 12.5 %, about 13 %, about 13.5 %, about 14 %, about 14.5 %, about 15 %, about 15.5 %, about 16 %, about 16.5 %, about 17 %, about 17.5 %, about 18 %, about 18.5 %, about 19 %, about 19.5 %, or about 20 %, by volume, including any value therebetween.
  • Non-limiting examples of long chain aliphatic alcohol are fatty alcohols, which include, without limitation, lauryl alcohol, stearyl alcohol, and oleyl alcohol.
  • the long chain aliphatic alcohol is lauryl alcohol.
  • 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. In some embodiments of the present invention, the formulation is characterized by pH below 2. In some embodiments of the present invention, the formulation is characterized by pH below 1.
  • 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).
  • the formulation is, for example, without being limited thereto, a personal care formulation, comprising:
  • 3-phenyl propanol in a concentration that ranges from 2% to 30% by volume;
  • an organic acid selected from the group consisting of: dehydroacetic acid (DHA), benzoic acid, and a combination thereof;
  • diol and/or triol the diol being selected from the group consisting of: 1,2-diol, 1,3-diol, and any combination thereof;
  • an emulsifier and/or alpha-dehydroxy acid an emulsifier and/or alpha-dehydroxy acid.
  • the disclosed formulation is devoid of 2-methyl-4-isothiazoline-3-one (MIT). In some embodiments, the disclosed formulation is devoid of 5-chloro-2-methyl-4- isothiazoline-3-one (CIT). In some embodiments, the disclosed formulation is devoid of a paraben compound. In some embodiments, the disclosed formulation is devoid of a formaldehyde compound. In some embodiments, the disclosed formulation is devoid of halogen. In some embodiments, the disclosed formulation is devoid of phenoxyethanol. In some embodiments, the disclosed formulation is devoid of two or more compounds selected from: MIT, CIT, a paraben compound, formaldehyde compound, phenoxyethanol, a compound comprising a halogen atom, and any derivative thereof.
  • by volume refers to the volumetric concentration of a substance in a formulation or mixture or solution or suspension or dispersion.
  • 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.
  • 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 oil-in-water or water-in-oil.
  • 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 gels.
  • 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 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, l
  • the formulation is characterized by resistance to discoloration. In some embodiments of the present invention, the formulation comprising lactic acid is characterized by resistance to discoloration. In some embodiments of the present invention, the formulation comprising lactic acid is characterized by resistance to discoloration in an atmospheric environment.
  • 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.
  • 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 effect the prevention of formation of a biofilm of bacterial, fungal and/or other cells, and/or to effect 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.
  • the biofilm is formed of bacterial cells (or from a bacterium).
  • a biofilm is formed of bacterial cells of Gram-positive and/or Gram- negative bacteria.
  • the disclosed formulation described herein exhibit anti-biofilm formation (ABF) activity and can thus prevent, retard or reduce the formation of a mass of a biofilm.
  • ABSF anti-biofilm formation
  • the activity of preventing or reducing the formation of a biofilm may be achieved by a substrate or an article incorporating the disclosed formulation.
  • the inhibition or reduction or retardation of formation of a biofilm assumes that the biofilm has not yet been formed, and hence the presence of the formulation or an article comprising the same is required also in cases where no biofilm is present or detected.
  • the term "preventing" in the context of the formation of a biofilm indicates that the formation of a biofilm 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 biofilm in a comparable situation lacking the presence of the formulation or an article containing same.
  • preventing means a reduction to at least 15 %, 10 % or 5 % of the appearance of the biofilm in a comparable situation lacking the presence of the formulation or an article containing same.
  • the term "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.
  • compositions, method 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.
  • exemplary is used herein to mean “serving as an example, instance or illustration”. Any embodiment described as “exemplary” is not necessarily to be construed as preferred or advantageous over other embodiments and/or to exclude the incorporation of features from other embodiments.
  • a compound or “at least one compound” may include a plurality of compounds, including mixtures thereof.
  • range format is merely for convenience and brevity and should not be construed as an inflexible limitation on the scope of the invention. Accordingly, the description of a range should be considered to have specifically disclosed all the possible subranges as well as individual numerical values within that range. For example, 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.
  • Microbiological broth TSB Tryptic soy broth
  • DIFCO-Sabouraud Dextrose broth supplied by Bactochem (ISRAEL).
  • Tween 20 Polysorbate 20
  • Lecithin provided by Sigma- Aldrich (ISRAEL).
  • Microorganisms E. coli ATCC 8739, P. aeruginosa ATCC 9027, S. aureus ATCC
  • the microplate are CELLSTAR- 96 well cell culture plate from Greiner bio-one.
  • 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.
  • MIC evaluation test with A. niger was performed in test tubes. Growth in this case is visually evaluated. 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.
  • 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 ofmicroorganisms 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
  • the antimicrobial preservative effectiveness was performed in a face cream with a blend of composition as in sample 1. 0.1% EDTA was added to the face cream independently of the blend.
  • sample tested is face cream and the preservation is 1 % of the sample (referred herein as "Sample 1 ”) as detailed hereinbelow, +0.1 % EDTA.
  • the pH is 5.7
  • Percent hereinbelow refers to the corresponding concentration, by volume.
  • Sample 1 Benzoic acid- 5.5%; DHA- 2.5%; SLL -1 %; 3-Phenylpropanol-17%; and Propyleneglycol- 74%.
  • Table 1 below presents the results of Minimum Inhibition Concentration (MIC) for Sample 1 : Table 1
  • Table 2 shows the antimicrobial preservative effectiveness (Challenge test) performed in a face cream with a blend of composition as in sample 1 :
  • Table 3 presents the antimicrobial Preservative Effectiveness Test for Sample 1 (1%) + 0.1 % EDTA.
  • the antimicrobial preservative effectiveness was performed in a face cream with a blend of composition as in sample, wherein 0.1% EDTA was added to the face cream of the blend, independently.
  • E. coli ATCC P.aeruginosa 5. aureus C. albicans A. niger 8739 ATCC 9027 ATCC 6538 ATCC 10231 ATCC 16404
  • Sample 2 Benzoic acid- 5.5%; DHA -3%; SLL -3%; 3-Phenylpropanol-17%; and Propyleneglycol- 71.5%.
  • SLL was increased to 3%, and as a consequence DHA concentration reached 3%.
  • Sample 3 Benzoic acid- 5.5%; DHA -3%; Sorbic acid-2%; SLL -3%; 3-Phenylpropanol-17%; and Propyleneglycol- 69.5%.
  • Sample 4 Benzoic acid- 5.5%; DHA -3%; Sorbic acid- 2%; SLL -3%; Lauryl alcohol- 10%;
  • lauryl alcohol a fatty acid alcohol
  • Sample 6 Benzoic acid- 5.5%; DHA-3%; Sorbic acid-2%; 3-Phenylpropanol- 17%; Lactic acid- 5%; and Propylene glycol- 67.5%.
  • This blend contains sorbic acid, 2%, in addition to the composition of sample 6 hereinabove.
  • Citric acid-0.35% Benzoic acid- 5.5%; DHA -3%; Sorbic acid-2%; SLL -3%; 3-Phenylpropanol- 17%; Propyleneglycol- 69.15%; and Anhydrous Citric acid-0.35%.
  • This blend has a 0.35% citric acid added to the blend described in sample 3 hereinabove. The main utility of this is to reduce discoloration.
  • Table 9 presents a blend, with the addition of Peg 40 hydrogenated Castol oil 3% (Replacing the SLL 3%).
  • Blends containing 1-Phenylpropanol, 2-Phenylpropanol, 3-Phenylpropanol and Phenoxyethanol were also prepared and their anti-micro-organic activities were tested as well (see Table 13). As further presented in Table 13, the tests were performed on Candida albicans (Yeast), Aspergillus niger (Mold), Staphylococcus aureus (Gram +), Pseudomonas aeruginosa (Gram -), and E. Coli (Gram -). Table 13 Microorganism/ E. Coli Pseudomonas Staphylococcus Aspergillus Candida
  • Formula 17.1 4800 6000 500 1500 1000 propanol -17%
  • the preservative line (Formulae 17, 17.1, and 17.2) is a broad spectrum, effective against Gram -, Gram +, yeast and molds.
  • a sample of a face cream was tested with a preservation
  • the method applied was based on the USP 30 guidelines for antimicrobial effectiveness testing.
  • the microorganisms used for the test are listed in the Table 14 below. Five samples of the product are inoculated with 1 microorganism each. The volume of the culture is calculated to yield a count of 10 5 - 10 6 CFU/g.
  • a four weeks follow-up was performed. Each product was sampled once a week and a viable count was performed.
  • Polysorbate 20 and Soya Lecithin were added to the culture media in order to neutralize the preservatives and enable the recovery of all living microorganisms.
  • the method applied was based on the USP 30 guidelines for antimicrobial effectiveness testing.
  • the microorganisms used for the test were listed in the Table 15 below. Five samples of the product are inoculated with 1 microorganism each. The volume of the culture is calculated to yield a count of 10 5 - 10 6 CFU/gr.
  • the blends being solutions of organic acids in organic solvents, were verified regarding their physical stability and particularly their resistance to crystallization according to the temperature, during storage and shipping.
  • the disclosed blends are an ideal preservative solution for the wet wipes market. They display a broad spectrum anti-micro-organic activity, are physically stable and suitable for mass market production at a competitive price.

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Abstract

Personal care formulations comprising: 3-phenyl propanol, an organic acid (e.g., dehydroacetic acid (DHA), benzoic acid), a diol or triol, an emulsifier and/or alpha-dehydroxy acid, are disclosed. A processes of preparing the disclosed formulations, articles containing same, and uses thereof in, e.g., for reducing or preventing growth of microorganisms are further disclosed.

Description

ANTIMICROBIAL PRESERVATIVE COMPOSITIONS
This application claims priority from U.S. Patent Application No. 62/084,002, filed on November 25, 2014. The content of the above document is incorporated by reference as if fully set forth herein.
FIELD OF INVENTION
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, containing 3-phenylpropanol, processes of preparing same, articles containing same, and uses thereof in, for example, reducing or preventing growth of microorganisms.
BACKGROUND OF THE INVENTION
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.
Preservation of personal care products from microbial contamination has become a difficult task since the available approved antimicrobials are very few and those which have good antimicrobial activity are quite toxic. Consumers seek for products for topical applications being free from toxic antimicrobials that can be used as preservatives.
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.
Hospital-acquired (nosocomial) infections occur even when good hygiene and sterile technique is followed, although the incidence is reduced. Despite even the most rigorous aseptic procedures, people cannot be completely isolated from infectious agents.
The widespread use of antibacterial compositions indicates the importance consumers place on controlling bacteria and other microorganism populations on skin. It is important, however, that antibacterial compositions provide a substantial and broad spectrum reduction in microorganism populations quickly and without problems associated with toxicity and skin irritation. In particular, 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.
Despite being successful in controlling or eliminating bacterial infections, widespread use of antibiotics both in human medicine and as a feed supplement in poultry and livestock production has led to drug resistance in many pathogenic bacteria (McCormick J. B., Curr Opin Microbiol 1: 125- 129, 1998). The evolution and spread of resistance genetic determinants, multidrug resistant (MDR) bacteria that cause life-threatening infections have been increasingly emerged (A. P. Magiorakos et al. Clin. Microbiol. Infect. 2012, 18, 268), and as such, the effectiveness of antibiotics has greatly diminished in the last decade. Furthermore, as resistance spreads among bacteria, there is great concern that antibiotics treatment will become increasingly less effective and, in some cases, completely ineffective.
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.
Currently, a number of blends are available for preservation of personal care products where synergy between antimicrobials is exploited in lowering the concentration of individual ingredient. Another great advantage is that the microbes cannot develop resistance very easily if they are attacked by a combination of antimicrobials.
R. M. E. Richards, and R. J. McBride. ( . Pharm. Sci., 62, 2035-7, 2006) disclose the actions of benzalkonium chloride and chlorhexidine acetate in combination with benzyl alcohol, 2- phenylethanol, or 3-phenylpropanol, evaluated at subinhibitory concentrations by measuring the growth rates of Pseudomonas aeruginosa NCTC 6750 with phenylpropanol showing the greatest enhancement and benzyl alcohol showed the least enhancement.
WO2007/071089 discloses personal care products and compositions that comprise at least one preservative compound selected from the group consisting of phenoxyethanol, 2-phenyl ethanol, phenoxypropanol, 3-phenylpropanol and benzylalcohol, in a total concentration of 0.1 to 1% (w/w).
WO2006/081071 discloses a stable skin care composition comprising dehydroacetic acid and a dermatologically acceptable carrier comprising at least one oil.
U.S. Patent Application having Publication No. 2006/0093634 discloses a color stable personal care composition which includes one or more additional anti-microbial agents (e.g., preservatives) and other suitable antimicrobial agents which include sorbic acid, benzoic acid, and salts thereof, and mixtures thereof.
Lately, the European Commission prohibited DEA in cosmetics and restricts products with MEA to < 0.5% amine content due to concerns about formation of carcinogenic nitrosamines. Specific Low cost products, which are free of the chemicals of concern, are therefore desired.
SUMMARY OF THE INVENTION
The present inventors have surprisingly uncovered that personal care formulations comprising up to 30% phenylpropanol, and more particularly, but not exclusively, 3-phenylpropanol, can be readily prepared, and that such formulations exhibit exceptional antimicrobial and anti-biofouling activity.
According to one aspect, the present invention provides a personal care formulation comprising: 3-phenyl propanol in a concentration that ranges from 2% to 30% by volume; an organic acid selected from the group consisting of: dehydroacetic acid (DHA), benzoic acid, and a combination thereof; a diol and/or triol, the diol being selected from the group consisting of: 1,2-diol, 1,3-diol, and any combination thereof; and an emulsifier and/or alpha-dehydroxy acid.
According to some embodiments of the present invention, the personal care formulation comprises a combination of DHA and benzoic acid.
According to some embodiments of the present invention, the personal care formulation comprises 3-phenyl propanol at a concentration that ranges from 2% to 30% by volume; DHA at a concentration that ranges from 0.1% to 5% by volume, and benzoic acid at a concentration that ranges from about 0.1% to 7 % by volume, diol and/or triol at a concentration of up to 90 % by volume; and an one emulsifier and/or lactic acid at a concentration that ranges from 0.1% to 10 % by volume.
According to some embodiments of the present invention, the 1,2 diol is propylene glycol. According to some embodiments of the present invention, the 1,3 diol is selected from the group consisting of: 1,3-butanediol, and 1,3-propandiol. According to some embodiments of the present invention, the triol is glycerol.
According to an aspect of some embodiments of the present invention, the emulsifier is selected from the group consisting of: 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, polyethoxylated fatty acids, polyethylene glycol glycerol fatty acid esters, alcohol-oil transesterification products, polyglycerized fatty acids, propylene glycol fatty acid esters, mono-and diglycerides, sterol and sterol derivatives, polyethylene glycol sorbitan fatty acid esters, polyethylene glycol alkyl ethers, sugar esters, polyethylene glycol alkyl phenols, polyoxyethylene-polyoxypropylene block copolymers, sorbitan fatty acid esters, low alcohol fatty acid esters, ionic surfactants, and mixtures thereof; and any combination thereof. According to some embodiments of the present invention, the emulsifier is SLL.
According to some embodiments of the present invention, the alpha-dehydroxy acid is lactic acid and/or citric acid. According to one embodiment, the alpha-dehydroxy acid is citric acid. According to another embodiment, the alpha-dehydroxy acid is lactic acid. According to embodiments, the personal care formulation is characterized by resistance to discoloration in an atmospheric environment.
According to some embodiments, the personal care formulation further comprises citric acid at a concentration up to 2%, by volume.
According to some embodiments of the present invention, the personal care formulation, further comprises sorbic acid, at a concentration that ranges from about 1.5 % to about 5 % by volume.
According to some embodiments, the personal care formulation further comprises an aliphatic alcohol at a concentration that ranges from 1 % to 15 % by volume, with the aliphatic alcohol having at least 10 carbon atoms in its backbone chain. According to some embodiments of the present invention, the aliphatic alcohol is lauryl alcohol.
According to another aspect, the present invention provides an article comprising the personal care formulation of the invention. According to some embodiments of, 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. According to some embodiments of the present invention, the article is selected from the group consisting of: paste, cream, lotion, foam, gel, emulsion, an ointment, and soap.
According to an aspect of some embodiments of the present invention, the personal care formulation is for pharmaceutical, cosmetic and/or cosmeceutical use.
According to another aspect, 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 the article with the personal care formulation.
According to some embodiments of the present invention, the microorganism is bacteria, fungi, or mold. According to some embodiments of the present invention, the bacteria are Gram positive bacteria selected from the group consisting of: Staphylococcus aureus, Staphylococcus epidermidis, and Bacillus cereus. According to some embodiments of the present invention, the bacteria are Gram negative bacteria selected from the group consisting of: Escherichia coli, Pseudomonas aeuruginosa, and Burkholderia cepacia. According to some embodiments, said fungi are Candida albicans. According to some embodiments, the molds are Aspergillus niger.
According to an aspect of some embodiments of the present invention, there is provided a process of preparing the personal care composition of the invention, the process comprising subjecting a mixture of: 3-phenyl propanol; an organic acid selected from the group consisting of: (DHA) and benzoic acid, and any combination thereof; a diol and/or triol; and an emulsifier and/or lactic acid.
Unless otherwise defined, all technical and/or scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which the invention pertains. Although methods and materials similar or equivalent to those described herein can be used in the practice or testing of embodiments of the invention, exemplary methods and/or materials are described below. In case of conflict, the patent specification, including definitions, will control. In addition, the materials, methods, and examples are illustrative only and are not intended to be necessarily limiting.
DETAILED DESCRIPTION OF THE INVENTION
The present invention, in some embodiments thereof, relates to personal care compositions and, more particularly, but not exclusively, to stable personal care formulations with antimicrobial (also referred to as "anti-micro-organic") activity, containing 2-30% 3-phenylpropanol, processes of preparing same, articles containing same, and uses thereof in, for example, reducing or preventing growth of microorganisms.
Before explaining at least one embodiment of the invention in detail, it is to be understood that the invention is not necessarily limited in its application to the details set forth in the following description or exemplified by the Examples. The invention is capable of other embodiments or of being practiced or carried out in various ways.
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.
The present inventors have designed non-toxic antimicrobial formulations (also referred to as "blends") comprising 3-phenyl propanol in concentration lower than 30 % for use as cosmetic composition and for various articles. Non-limiting examples of such uses can include personal hygiene and treatment of specific skin regions -of-interest. In some embodiments, the disclosed formulations (e.g., formulations comprising 3-phenylpropanol) are both efficient and cost-effective antimicrobial formulations.
As demonstrated in the Examples section that follows, the present inventors have shown that formulations comprising 3-phenyl propanol, at least one organic acid, diol or triol, and at least one emulsifier or lactic acid, all of which being at certain volumetric ratios, exhibit an improved stability as well as improved antimicrobial and/or antibiofilm activities, compared to other formations comprising different materials from the invented formulations or from formulations comprising the same materials but having different volumetric ratios thereof. The present inventors have also shown that the disclosed formulation can be used to impart to articles the antimicrobial and/or antibiofilm activities.
The formulation:
According to an aspect of some embodiments of the present invention there is provided a stable personal care composition. In some embodiments the composition is a stable preservative. In some embodiments, the stable personal care formulation comprises: 3-phenyl propanol (also known as 3- phenyl 1- propanol) at a concentration of e.g., about 2%, about 5%, about 10%, about 15%, about 20%, about 25%, about 30%, about 35%, by volume, including any value therebetween. In some embodiments of the present invention, the personal care formulation further comprises phenethyl alcohol (also known as 2-phenylethanol) at a concentration of e.g., about 2%, about 5%, about 10%, about 15%, about 20%, about 25%, about 30%, about 35%, by volume, including any value therebetween. In some embodiments of the present invention, the personal care formulation comprises: 1-phenyl 1-propanol at a concentration of e.g., about 2%, about 5%, about 10%, about 15%, about 20%, about 25%, about 30%, about 35%, by volume, including any value therebetween.
In some embodiments, the personal care formulation comprises at least one organic acid. In some embodiments, the personal care formulation comprises a diol. In some embodiments, the personal care formulation comprises at least one emulsifier and/or alpha-dehydroxy acid. In some embodiments the alpha-dehydroxy acid is selected from the group consisting of: lactic acid and citric acid, and combination thereof. In some embodiments the alpha-dehydroxy acid is lactic acid. In some embodiments the alpha-dehydroxy acid is citric acid. In some embodiments the alpha- dehydroxy acid is a mixture of lactic acid and citric acid.
Non-limiting exemplary organic acids are: dehydroacetic acid (DHA), benzoic acid, and any combination thereof.
In some embodiments, the personal care formulation comprises: benzoic acid, DHA, 3- Phenylpropanol, Propyleneglycol, Tween, Lactic acid, PEG-40 Hydrogenated castor oil, Lauryl alcohol, Sorbic acid, Citric acid, and SLL.
In some embodiments, the benzoic acid is at a concentration of: e.g., 0%, 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, or 10%, including any value therebetween. In some embodiments, the DHA is at a concentration of e.g., 0.1%, 0.5%, 1%, 1.5%, 2%, 2.5%, 3%, 3.5%, 4%, 4.5%, or 5%, including any value therebetween. In some embodiments, the sorbic acid is at a concentration of e.g., 0%, 0.5%, 1%, 1.5%, 2%, 2.5%, 3%, 3.5%, or 4%, including any value therebetween. In some embodiments, the SLL is at a concentration of e.g., 0%, 0.5%, 1%, 1.5%, 2%, 2.5%, 3%, 3.5%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 11% or 12%, including any value therebetween, wherein, in some embodiments, any other emulsifier or lactic acid may be used. In some embodiments, the 3-Phenylpropanol is at a concentration of e.g., 1.5%, 2%, 4%, 6%, 8%, 10%, 12%, 14%, 16%, 18%, 20%, 22%, 24%, 26%, 28%, 30%, 32%, or 35%, including any value therebetween. In some embodiments, the propyleneglycol is at a concentration of e.g., 0%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 95%, 99%, including any value therebetween, wherein, in some embodiments, any other 1,2 or 1,3 diol may be used instead of propyleneglycol. In some embodiments, Tween 20 is at a concentration of e.g., 0%, 0.5%, 1%, 1.5%, 2%, 2.5%, 3%, 3.5%, 4%,5%, 6%, 7%, 8%, 9%, 10%, 11% or 12%, including any value therebetween. In some embodiments, the lactic acid is at a concentration of: e.g., 0%, 0.5%, 1%, 1.5%, 2%, 2.5%, 3%, 3.5%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 11% or 12%, including any value therebetween, wherein if the concentration of the emulsifier, e.g., SLL, is 0%, the lactic acid is at concentration higher than 0%. In some embodiments, the lauryl alcohol is at a concentration of e.g., 0%, 0.5%, 1%, 1.5%, 2%, 2.5%, 3%, 3.5%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, or 20%, including any value therebetween. In some embodiments, the PEG-40 Hydrogenated castor oil is at a concentration of e.g., 0%, 0.5%, 1%, 1.5%, 2%, 2.5%, 3%, 3.5%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, or 15, including any value therebetween. In some embodiments, the citric acid is at a concentration of: e.g., 0%, 0.1%, 0.2%, 0.3%, 0.4%, 0.5%, 0.6%, 0.7%, 0.8%, 0.9%, 1%, 1.1%, 1.2%, 1.3%, 1.4%, or 1.5%, including any value therebetween.
In exemplary embodiments of the present invention, the formulation is or comprises (percentages below refers to concentration, by volume; the percentage below may vary within ±5%): Benzoic acid- 5.5%; DHA- 2.5%; SLL -1%; 3-Phenylpropanol-17% and Propyleneglycol- 74%.
In additional exemplary embodiments of the present invention, the formulation is or comprises: Benzoic acid- 5.5%; DHA -3%; SLL -3%; 3-Phenylpropanol-17%; and Propyleneglycol- 71.5%.
In additional exemplary embodiments of the present invention, the formulation is or comprises: Benzoic acid- 5.5%; DHA -3%; Sorbic acid-2%; SLL -3%; 3-Phenylpropanol-17%; and Propyleneglycol- 69.5%.
In additional exemplary embodiments of the present invention, the formulation is or comprises: Benzoic acid- 5.5%; DHA -3%; Sorbic acid- 2%; SLL -3%; Lauryl alcohol- 10%; 3- Phenylpropanol-17%; and Propylene glycol-59.5%.
In additional exemplary embodiments of the present invention, the formulation is or comprises: Benzoic acid- 5.5%; DHA-3%; 3-Phenylpropanol- 17%; Lactic acid- 5%; and Propylene glycol- 69.5%.
In additional exemplary embodiments of the present invention, the formulation is or comprises: Benzoic acid- 5.5%; DHA-3%; Sorbic acid-2%; 3-Phenylpropanol- 17%; Lactic acid- 5%; and Propylene glycol- 67.5%.
In additional exemplary embodiments of the present invention, the formulation is comprises: Benzoic acid- 5.5%; DHA -3%; Sorbic acid-2%; SLL -3%; 3-Phenylpropanol- 17%; Propyleneglycol- 69.15%; and Anhydrous Citric acid-0.35%.
In additional exemplary embodiments of the present invention, the formulation is or comprises: Benzoic acid- 5.5%; DHA -3%; Sorbic acid- 2%; Tween 20 -3%; Phenylpropanol-17%; and Propyleneglycol- 69.5%.
In some embodiments of the present invention, as further described hereinabove, the formulation comprises a diol. As used herein, the term "diol" is intended to include any molecule having at least two hydroxyl groups. The term "diol" does not exclude the possibility of additional hydroxyl groups also being present, and therefore specifically includes triols, polyols and the like.
Examples of diols of the present invention encompasses, but are not limited to, propane- 1,2- diol, propane- 1,3-diol, butane- 1 ,2-diol, butane- 1,3 -diol, butane- 1,4-diol, butane-2,3-diol, 2- methylpropane-1,2- diol, 2-methylpropane- 1,3-diol, 2-hydroxymethyl- 1 -propanol, pentane- 1 ,2-diol, pentane-2,3-diol, 2-hydroxymethyl-l-butanol, 2-methylbutane- 1 ,2-diol, 3- methylbutane- 1 ,2-diol, 2- methylbutane- 1,3 -diol, 3-methylbutane-l,3-diol, 2- methylbutane- 1,4-diol, and hexane- 1 ,2-diol.
In some embodiments of the present invention, the diol is 1,2- diol.
In another exemplary embodiments of the present invention the 1,3- diol is 1,3-butanediol, and
1, 3-propandiol.
In another exemplary embodiments of the present invention the 1 ,2- diol is propane- 1 ,2-diol, also termed "propylene glycol".
In some embodiments of the present invention, the diol is also a triol. In exemplary embodiments the triol is glycerol.
In some embodiments of the present invention, the diol is at a concentration of e.g., up to 5 %, 10 %, 20 %, 30 %, 40 %, 50 %, 60 %, 70 %, 80 %, 90 %, 95 %, or 99 %, by volume, including any value therebetween.
As noted hereinabove the formulation of the invention may include an emulsifier.
As used herein and in the art, the term "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.
In some embodiments of the present invention, the emulsifier is SLL. As described hereinabove, in some embodiments of the present invention, the personal care formulation comprises one or more organic acids.
In some embodiments of the present invention, the formulation comprises a lactic acid instead of one or more emulsifiers. In some embodiments of the present invention, the formulation comprises a lactic acid in addition to one or more emulsifiers.
In some embodiments of the present invention, the organic acids are selected from DHA and benzoic acid and any combination thereof.
In some embodiments, the DHA 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 volume, including any value therebetween.
In some embodiments, the benzoic acid 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 volume, including any value therebetween.
In some embodiments of the present invention, the formulation further comprises sorbic acid. In some embodiments of the present invention, the sorbic acid is at a concentration of e.g., about 0.5 %, 1 %, 1.5 %, 2 %, 2.5 %, 3 %, 3.5 %, 4 %, 4.5%, 5 %, 5.5 %, 6 %, 6.5%, 7 %, 7.5 %, 8 %, 8.5 %, 9 %, or 10 %, by volume, including any value therebetween.
In some embodiments of the present invention, the formulation comprising sorbic acid further comprises ethylenediamine tetra acetate (EDTA). In some embodiments of the present invention, the EDTA is at a concentration of e.g., about 0.005 %, about 0.006 %, about 0.007 %, about 0.008 %, about 0.009 %, about 0.01 %, about 0.02 %, about 0.03 %, about 0.04 %, about 0.05 %, about 0.06 %, about 0.07 %, about 0.08 %, about 0.09 %, about 0.1 %, about 0.15 %, or about 0.2 %, by volume, including any value therebetween.
In some embodiments, the disclosed formulation is added to a face cream.
In some embodiments, 0.1% EDTA is added to the face cream comprising any formulation of the present invention. In exemplary embodiments, 0.1% EDTA is added to a formulation comprising Benzoic acid- 5.5%; DHA- 2.5%; SLL -1%; 3-Phenylpropanol-17%; and Propyleneglycol- 74%, by volume (percentage may vary between ± 5%).
In some embodiments of the present invention, the formulation further comprises at least one type of long chain aliphatic alcohol. As used herein, "long chain aliphatic alcohols" are non-aromatic compounds which include, but are not limited to, alkanols that comprise at least 10 carbon atoms in its backbone chain and at least one hydroxyl group being bound thereto.
In some embodiments of the present invention, the long chain aliphatic alcohol is at a concentration of e.g., about 0.5 %, about 1 %, about 1.5 %, about 2 %, about 2.5 %, 3 about %, about 3.5 %, about 4 %, about 4.5%, about 5 %, about 5.5 %, about 6 %, about 6.5%, about 7 %, about 7.5 %, about 8 %, about 8.5 %, about 9 %, about 10 %, about 10.5 %, about 11 %, about 11.5 %, about 12 %, about 12.5 %, about 13 %, about 13.5 %, about 14 %, about 14.5 %, about 15 %, about 15.5 %, about 16 %, about 16.5 %, about 17 %, about 17.5 %, about 18 %, about 18.5 %, about 19 %, about 19.5 %, or about 20 %, by volume, including any value therebetween.
Non-limiting examples of long chain aliphatic alcohol are fatty alcohols, which include, without limitation, lauryl alcohol, stearyl alcohol, and oleyl alcohol. In some embodiments of the present invention, the long chain aliphatic alcohol is lauryl alcohol.
In some embodiments of the present invention, 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. In some embodiments of the present invention, the formulation is characterized by pH below 2. In some embodiments of the present invention, the formulation is characterized by pH below 1.
In some embodiments of the present invention, 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.
As used herein, the terms "formulation", or "blend", which are used hereinthroughout interchangeably, refer 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). In some embodiments, the formulation is, for example, without being limited thereto, a personal care formulation, comprising:
3-phenyl propanol in a concentration that ranges from 2% to 30% by volume;
an organic acid selected from the group consisting of: dehydroacetic acid (DHA), benzoic acid, and a combination thereof;
a diol and/or triol, the diol being selected from the group consisting of: 1,2-diol, 1,3-diol, and any combination thereof; and
an emulsifier and/or alpha-dehydroxy acid.
In some embodiments, the disclosed formulation is devoid of 2-methyl-4-isothiazoline-3-one (MIT). In some embodiments, the disclosed formulation is devoid of 5-chloro-2-methyl-4- isothiazoline-3-one (CIT). In some embodiments, the disclosed formulation is devoid of a paraben compound. In some embodiments, the disclosed formulation is devoid of a formaldehyde compound. In some embodiments, the disclosed formulation is devoid of halogen. In some embodiments, the disclosed formulation is devoid of phenoxyethanol. In some embodiments, the disclosed formulation is devoid of two or more compounds selected from: MIT, CIT, a paraben compound, formaldehyde compound, phenoxyethanol, a compound comprising a halogen atom, and any derivative thereof.
The term "by volume", as used hereinthroughout, refers to the volumetric concentration of a substance in a formulation or mixture or solution or suspension or dispersion.
As used herein, the term "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.
Herein the term "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. For example, 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.
As used herein the terms "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. For example, and without limitation, 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.
As used herein, the phrase "personal care" refers to compositions that can be formulated in various cosmetic and pharmaceutical consumer products utilizing a variety of delivery systems and carrier bases. Such 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.
In some embodiments, 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). As with other carriers or vehicles, an ointment base should be inert, stable, nonirritating and nonsensitizing. As explained in Remington: The Science and Practice of Pharmacy, 19th Ed., Easton, Pa.: Mack Publishing Co. (1995), pp. 1399-1404, 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 oil-in-water or water-in-oil. 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 gels. 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 Carbopol™. Other types of preferred polymers in this context are 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. In order to prepare a uniform gel, 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. Upon delivery to the skin, 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 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, luffa particles, polyethylene balls, mica, pH adjusters, processing aids, and combinations thereof. In some embodiments of the present invention, the formulation is characterized by resistance to discoloration. In some embodiments of the present invention, the formulation comprising lactic acid is characterized by resistance to discoloration. In some embodiments of the present invention, the formulation comprising lactic acid is characterized by resistance to discoloration in an atmospheric environment.
As used herein, "discoloration" 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.
Articles comprising the Formulation:
According to an aspect of some embodiments of the present invention there is provided an article which comprises any one of the personal care formulation described herein.
Some embodiments of this aspect of present embodiments are included hereinabove, under "The Formulation", and form an integral part of embodiments relating to "Articles comprising the Formulation".
According to an aspect of some embodiments of the present invention, there is provided 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.
According to an aspect of some embodiments of the present invention, 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.
As used herein, "preservative" is used to prevent the growth of bacteria, fungi and/or molds in any personal care composition or formulation.
According to a further aspect of some embodiments of the present invention, there is provided 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.
In some embodiments there is provided a method of treating a medical, cosmeceutical or cosmetic condition treatable by a topical or transdermal administration, the method 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.
The phrases "topical" "topical administrations" and or any grammatical derivative thereof, is meant to encompass 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.
Hence, according to some embodiments of the present invention, 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.
Topical bodily sites include skin, mucosal tissue, eye, ear, nose, mouth, rectum and vagina.
In some embodiments, there is provided 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.
In some embodiments of the present invention, 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.
In some exemplary embodiments of the present invention, the article is in the form of paste, cream, lotion, foam, gel, emulsion, an ointment, or soap.
In some embodiments, the personal care formulation of the present invention can be used to treat skin tissue or on damaged or unhealthy skin tissue.
The phrase "damaged or unhealthy skin tissue" as used herein refers to a deviation from healthy functional skin tissue. In the case of 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).
The phrase "healthy skin tissue" as used herein 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.
The term "damaged" as used herein, or any grammatical derivative thereof, 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's disease, dermatofibroma, Discoid Lupus Erythematosus, nummular eczema, atopic eczema, dyshidrotic eczema, hand eczema, Multiforme Erythema Nodosum, Fordyce's Condition, Folliculitis Keloidalis Nuchae, Folliculitis, Granuloma Annulare, Grover's Disease, heat rash, herpes simplex, herpes zoster (shingles), Hidradenitis Suppurativa, Hives, Hyperhidrosis, Ichthyosis, Impetigo, Keratosis Pilaris, Keloids, Keratoacanthoma, Lichen Planus, Lichen Planus Like Keratosis, Lichen Simplex Chronicus, Lichen Sclerosus, Lymphomatoid Papulosis, Lupus of the Skin, Lyme Disease, Lichen Striatus, Myxoid Cysts, Mycosis Fungoides, Molluscum Contagiosum, Moles, Nail Fungus, Necrobiosis Lipoidica Diabeticorum, Nummular Dermatitis, Onychoschizia, Onychomycosis, Pityriasis Lichenoides, Pityriasis Rosea, Pityriasis Rubra Pilaris, Plantar Warts, Poison Ivy, Poison Oak, Pompholyx, Pseudofolliculitis Barbae, Pruritus Ani and Pityriasis Alba.
Antimicrobial Activity:
According to an aspect of some embodiments of the present invention there is provided 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. The method 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.
Some embodiments of this aspect of present embodiments are included hereinabove, under
"The Formulation", and under "Articles comprising the Formulation" and form an integral part of embodiments relating to "Antimicrobial Activity".
Herein "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.
Herein, 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. Thus, 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.
An article, according to these embodiments, can be also a living tissue, for example, a skin or mucosal tissue, as described herein.
In the context of the present embodiments, 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. It is contemplated that in some embodiments, the formulations of the present invention may be easily applied to susceptible surfaces in advance of and/or during exposure to a microbial organism.
In some embodiments, the microorganism comprises bacterial cells of bacteria such as, for example, Gram-positive and Gram-negative bacteria.
In some embodiments, the Gram-positive bacteria are Staphylococcus aureus, Staphylococcus epidermidis, and Bacillus cereus. In some embodiments, the Gram-negative bacteria are Escherichia coli, Pseudomonas aeuruginosa, and Burkholderia cepacia.
In some embodiments of the present invention, the microorganism is fungi e.g., Candida albicans and Aspergillus niger.
The term "biofilm", as used herein, 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.
In the context of the present embodiments, 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.
In the context of the present embodiments, 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.
The phrases "antibiofilm formation activity" refers to the capacity of a substance to effect the prevention of formation of a biofilm of bacterial, fungal and/or other cells, and/or to effect 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.
In some embodiments, the biofilm is formed of bacterial cells (or from a bacterium).
In some embodiments, a biofilm is formed of bacterial cells of Gram-positive and/or Gram- negative bacteria.
In some embodiments, the disclosed formulation described herein exhibit anti-biofilm formation (ABF) activity and can thus prevent, retard or reduce the formation of a mass of a biofilm.
In some embodiments of the present invention, the activity of preventing or reducing the formation of a biofilm, may be achieved by a substrate or an article incorporating the disclosed formulation. The inhibition or reduction or retardation of formation of a biofilm assumes that the biofilm has not yet been formed, and hence the presence of the formulation or an article comprising the same is required also in cases where no biofilm is present or detected.
As used herein, the term "preventing" in the context of the formation of a biofilm, indicates that the formation of a biofilm 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 biofilm in a comparable situation lacking the presence of the formulation or an article containing same. Alternatively, preventing means a reduction to at least 15 %, 10 % or 5 % of the appearance of the biofilm in a comparable situation lacking the presence of the formulation or an article containing same. Methods for determining a level of appearance of a biofilm are known in the art.
As used herein, the term "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. Alternatively, 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. Methods for determining a level of appearance of a microorganism cells are known in the art.
General:
It is expected that during the life of a patent maturing from this application many relevant formulations will be developed and the scope of the term formulation is intended to include all such new technologies a priori.
As used herein the term "about" refers to ± 10 %.
The terms "comprises", "comprising", "includes", "including", "having" and their conjugates mean "including but not limited to".
The term "consisting of" means "including and limited to".
The term "consisting essentially of" means that the composition, method 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. The word "exemplary" is used herein to mean "serving as an example, instance or illustration". Any embodiment described as "exemplary" is not necessarily to be construed as preferred or advantageous over other embodiments and/or to exclude the incorporation of features from other embodiments.
The word "optionally" is used herein to mean "is provided in some embodiments and not provided in other embodiments". Any particular embodiment of the invention may include a plurality of "optional" features unless such features conflict.
As used herein, the singular form "a", "an" and "the" include plural references unless the context clearly dictates otherwise. For example, the term "a compound" or "at least one compound" may include a plurality of compounds, including mixtures thereof.
Throughout this application, various embodiments of this invention may be presented in a range format. It should be understood that the description in range format is merely for convenience and brevity and should not be construed as an inflexible limitation on the scope of the invention. Accordingly, the description of a range should be considered to have specifically disclosed all the possible subranges as well as individual numerical values within that range. For example, 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.
Whenever a numerical range is indicated herein, it is meant to include any cited numeral
(fractional or integral) within the indicated range. The phrases "ranging/ranges between" a first indicate number and a second indicate number and "ranging/ranges from" a first indicate number "to" a second indicate number are used herein interchangeably and are meant to include the first and second indicated numbers and all the fractional and integral numerals therebetween.
As used herein the term "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.
As used herein, the term "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.
It is appreciated that certain features of the invention, which are, for clarity, described in the context of separate embodiments, may also be provided in combination in a single embodiment. Conversely, various features of the invention, which are, for brevity, described in the context of a single embodiment, may also be provided separately or in any suitable subcombination or as suitable in any other described embodiment of the invention. Certain features described in the context of various embodiments are not to be considered essential features of those embodiments, unless the embodiment is inoperative without those elements.
Various embodiments and aspects of the present invention as delineated hereinabove and as claimed in the claims section below find experimental support in the following examples.
EXAMPLES
Reference is now made to the following examples, which together with the above descriptions illustrate some embodiments of the invention in a non-limiting fashion.
EXAMPLE 1
PREPARATION OF THE FRMULATIONS
Materials:
3 -Phenyl propane, Benzoic acid, Dehydroacetic acid ( DHA ), Sorbic acid, Propylene glycol; Glycerol; Butylene glycol; Emulsifiers: Sodium lauroyl lactylate (SLL), Tween 20, PEG 40- hydrogenated castor oil, Cocoamide monoethanolamide, Potassium Cocoate, Sorbic acid, Face cream and EOT A.
General Procedure:
The following describes exemplary procedures:
In a typical procedure, 3-phenylpropanol was introduced first into the recipient, followed by the addition of propyleneglycol and then additional ingredients whether the emulsifiers and/or lactic acid. The organic acids were added at last until full dissolution. Room temperature (i.e. about 25 °C) is enough for solubilizing the materials, although a higher temperature like 45 °C would increase the rate of solubilization.
Exemplary formulations are described in Example 2 that follows, Samples 1 -9. EXAMPLE 2
ANTIMICROBIAL ACTIVITY
Materials:
Microbiological broth TSB (Tryptic soy broth) and DIFCO-Sabouraud Dextrose broth, supplied by Bactochem (ISRAEL).
Tween 20 (Polysorbate 20) and Lecithin, provided by Sigma- Aldrich (ISRAEL).
Microorganisms: E. coli ATCC 8739, P. aeruginosa ATCC 9027, S. aureus ATCC
6538, C. albicans ATCC 10231 and A. niger ATCC 16404; all microorganisms were purchased from Chemitec (ISRAEL).
Absorbance measurement at 600 nm, performed by ELISA Microplate reader BIO-
RAD Model 680.
The microplate are CELLSTAR- 96 well cell culture plate from Greiner bio-one.
General Procedure:
In exemplary procedure, 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.
In another exemplary procedure, MIC evaluation test with A. niger was performed in test tubes. Growth in this case is visually evaluated. 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.
After incubation, the series of dilution vessels was observed for microbial growth, usually indicated by turbidity and/or a pellet ofmicroorganisms 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.
For bacterial strains and Candida albicans microbial growth was estimated by reading O.D at 600 nm.
In another exemplary procedure, 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.
In exemplary procedure, five samples of the product were inoculated with 1 microorganism each. The volume of the culture was calculated to yield a count of 105 - 106 CFU/gr (CFU: colony forming unit).
In exemplary procedure, a 4 weeks follow-up was performed. Each product was sampled once a week and a viable count was performed. Polysorbate 20 and Soy Lecithin are added to the culture media in order to neutralize the preservatives and enable the recovery of all living microorganisms.
In exemplary procedure, the antimicrobial preservative effectiveness (Challenge test) was performed in a face cream with a blend of composition as in sample 1. 0.1% EDTA was added to the face cream independently of the blend.
In exemplary procedure, the sample tested is face cream and the preservation is 1 % of the sample (referred herein as "Sample 1 ") as detailed hereinbelow, +0.1 % EDTA. The pH is 5.7
Results:
Percent hereinbelow refers to the corresponding concentration, by volume.
Sample 1: Benzoic acid- 5.5%; DHA- 2.5%; SLL -1 %; 3-Phenylpropanol-17%; and Propyleneglycol- 74%.
It is noteworthy that with 1 % SLL, the maximum concentration that can be reached of DHA is 2.5%.
Table 1 below presents the results of Minimum Inhibition Concentration (MIC) for Sample 1 : Table 1
Minimum Inhibition Concentration (MIC; mg/1)
Microorganism/ Preservative Sample 1
E. coli (Gram -) 5000
Pseudomonas aeruginosa (Gram -) 5000 Staphylococcus aureus (Gram +) 2500
Aspergillus niger (Mold) 2500
Candida albicans (Yeast) 2500
Table 2 shows the antimicrobial preservative effectiveness (Challenge test) performed in a face cream with a blend of composition as in sample 1 :
Sample tested: Face cream
Preservation: 1 % Sample 1
pH: 5.7
Table 2
Figure imgf000027_0001
It can be concluded, without being bound by any particular theory, that the product meets the USP criteria for category 1 products.
Table 3 below presents the antimicrobial Preservative Effectiveness Test for Sample 1 (1%) + 0.1 % EDTA.
As noted hereinabove, the antimicrobial preservative effectiveness (Challenge test) was performed in a face cream with a blend of composition as in sample, wherein 0.1% EDTA was added to the face cream of the blend, independently.
Table 3
E. coli ATCC P.aeruginosa 5. aureus C. albicans A. niger 8739 ATCC 9027 ATCC 6538 ATCC 10231 ATCC 16404
Inoculum 8.5*105 9.7*105 7.8* 105 1.3* 105 2.0* 105 7 days 100 <100 <100 6.2* 103 3*102
14 days <10 <10 <10 <10 <10
21 days <10 <10 <10 <10 <10
28 days <10 <10 <10 <10 <10
It can be concluded, without being bound by any particular theory, that the product meets the USP criteria for category 1 products.
In additional exemplary procedures, Sample 2 was tested.
Sample 2: Benzoic acid- 5.5%; DHA -3%; SLL -3%; 3-Phenylpropanol-17%; and Propyleneglycol- 71.5%. In this example, SLL was increased to 3%, and as a consequence DHA concentration reached 3%.
Table 4 below presents the MIC (mg/1) results for Sample 2:
Table 4
Figure imgf000028_0001
It can be concluded, without being bound by any particular theory, that this small increase of DHA from 2.5% to 3% together with the increase of SLL from 1% to 3% improves significantly the antimicrobial activity of the blend.
In additional exemplary procedures, Sample 3 was tested.
Sample 3: Benzoic acid- 5.5%; DHA -3%; Sorbic acid-2%; SLL -3%; 3-Phenylpropanol-17%; and Propyleneglycol- 69.5%.
In this blend, addition of sorbic acid, 2% is evaluated.
Table 5 below presents the MIC (mg/1) results for Sample 3:
Table 5
Microorganism/ Preservative Sample 3 E. coli (Gram -) 4500
Pseudomonas aeruginosa (Gram -) 5500
Staphylococcus aureus (Gram +) 500
Aspergillus niger (Mold) 1500
Candida albicans (Yeast) 1200
It can be concluded, without being bound by any particular theory, that sorbic acid adds some antimicrobial activity against Candida albicans and Staphylococcus aureus.
In additional exemplary procedures, Sample 4 was tested.
Sample 4: Benzoic acid- 5.5%; DHA -3%; Sorbic acid- 2%; SLL -3%; Lauryl alcohol- 10%;
3-Phenylpropanol-17%; and Propylene glycol-59.5%.
In this sample, the addition of lauryl alcohol (a fatty acid alcohol) is evaluated.
Table 6 below presents the MIC (mg/1) results for Sample 4:
Table 6
Figure imgf000029_0001
It can be concluded, without being bound by any particular theory, that compared to the results of sample 1, long chain alcohols, such as lauryl alcohol, improve the antimicrobial activity of the blend, and in particular the activity on Staphylococcus aureus and Pseudomonas aeruginosa. In additional exemplary procedures, Sample 5 was tested.
Sample 5:
Benzoic acid- 5.5%; DHA-3%; 3-Phenylpropanol- 17%; Lactic acid- 5%; and propylene glycol- 69.5%
In this blend, no SLL is being used, but instead lactic acid at 5% concentration, by volume. The Concentration of DHA reached is still 3%. Table 7 below presents the MIC (mg/1) results for Sample 5:
Table 7
Figure imgf000030_0001
It can be concluded, without being bound by any particular theory, that a very decent antimicrobial activity is reached, even without the need of SLL.
In additional exemplary procedures, Sample 6 was tested.
Sample 6: Benzoic acid- 5.5%; DHA-3%; Sorbic acid-2%; 3-Phenylpropanol- 17%; Lactic acid- 5%; and Propylene glycol- 67.5%.
This blend contains sorbic acid, 2%, in addition to the composition of sample 6 hereinabove.
Table 8 below presents the MIC (mg/1) results for Sample 6:
Table 8
Figure imgf000030_0002
It can be concluded, without being bound by any particular theory, that sorbic acid at 2% concentration, by volume, contributes to the antimicrobial activity against Pseudomonas aeruginosa, Staphylococcus aureus and Candida albicans.
In additional exemplary procedures, Sample 7 was tested.
Sample 7:
Benzoic acid- 5.5%; DHA -3%; Sorbic acid-2%; SLL -3%; 3-Phenylpropanol- 17%; Propyleneglycol- 69.15%; and Anhydrous Citric acid-0.35%. This blend has a 0.35% citric acid added to the blend described in sample 3 hereinabove. The main utility of this is to reduce discoloration.
In additional exemplary procedures, Sample 8 was tested.
Sample 8:
Benzoic acid- 5.5% ; DHA -3%; Sorbic acid- 2%; Peg 40 hydrogenated Castol oil - 3%; Phenylpropanol-17% and Propyleneglycol- 69.5%.
Table 9 presents a blend, with the addition of Peg 40 hydrogenated Castol oil 3% (Replacing the SLL 3%).
Table 9 (MIC, mg/1):
Figure imgf000031_0001
In additional exemplary procedures, Sample 9 was tested.
Sample 9:
Benzoic acid- 5.5% ; DHA -3%; Sorbic acid- 2%; Tween 20 -3%; Phenylpropanol-17%; and Propyleneglycol- 69.5%.
In this blend, addition of Tween 20, 3% is evaluated (replacing the SLL 3%), and the MIC results are presented in Table 10 (MIC, mg/1) hereinbelow.
Table 10
Microorganism/ Preservative Results
E. coli (Gram -) 4000
Pseudomonas aeruginosa (Gram -) 6400
Staphylococcus aureus (Gram +) 4000
Aspergillus niger (Mold) 2000 Candida albicans (Yeast) 2500
The following Table 11 summarizes the MIC results of various formations of the invention:
Table 11
Figure imgf000033_0001
Figure imgf000034_0001
Figure imgf000035_0001
In additional exemplary procedures, the following compounds (see Table 12 below which presents the corresponding physical data) were compared e.g., with respect to their antimicrobial activity.
Table 12
2-Phenoxyethanol 3-Phenylpropanol l-Phenylpropanol 2-Phenylpropanol OH CHs
Chemical
Structure m.p 11 -13°C -18°C 4°C -37°C b.p 247°C 235-236°C 217-219°C 219-220°C
Mild
Weak ester like
Odor characteristic Cinnamon like Faint flowery
odor
odor
Masking Not in Cosmetic
Cosmetic ingredient
Preservative Perfuming Perfuming
Function database (used in
Solvent food)
The anti-micro-organic activities as detailed below, were tested to establish a comparison between the physical and anti-micro organic characteristics of blends which are including 2- phenoxyethanol on one hand and potential replacements on the other hand - namely the family of phenyl propanol compounds.
The anti-micro-organic activities of 1-Phenylpropanol, 2-Phenylpropanol, 3-Phenylpropanol and Phenoxyethanol were tested separately.
Blends containing 1-Phenylpropanol, 2-Phenylpropanol, 3-Phenylpropanol and Phenoxyethanol were also prepared and their anti-micro-organic activities were tested as well (see Table 13). As further presented in Table 13, the tests were performed on Candida albicans (Yeast), Aspergillus niger (Mold), Staphylococcus aureus (Gram +), Pseudomonas aeruginosa (Gram -), and E. Coli (Gram -). Table 13 Microorganism/ E. Coli Pseudomonas Staphylococcus Aspergillus Candida
Preservative/ Code (Gram -) aeruginosa aureus niger albicans Composition (%)
(Gram -) (Gram +) (Mold) (Yeast)
Phenoxyethanol 4500 4000 3500 3000 3500
100
1 -Phenyl 1-
1500 3000 1500 2000 4000
Propanol 100
2 -Phenyl 1-
1500 4000 3000 2000 2500
Propanol 100
3 -Phenyl 1-
1500 2000 2000 1200 2000
Propanol 100
Benzoic acid - 5.5%
DHA - 2.5%
Formula 17 5000 5000 2500 2500 2500 SLL - 1
3-Phenyl-l- propanol -17% Propylene Glycol - 74%
Benzoic a.- 5.5% DHA - 2.5% Lactic acid - 5% 3-Phenyl-l-
Formula 17.1 4800 6000 500 1500 1000 propanol -17%
Lauryl alcohol - 10%
Propylen Glycol - 60%
Benzoic acid - 5.5%
DHA - 3% Lactic acid - 5%
Formula 17.2 4000 4000 2000 2000 1000 3-Phenyl-l- Propanol -17% Propylene Glycol - 54.5%
Phenyl Ethanol - 15% Benzoic acid - 5.5%
DHA - 3% Lactic acid - 5%
9.1 MIO5000 6000 MIO5000 3000 2000 Phenoxyethanol -
17%
Phenylethanol - 15%
Propylen Glycol - 54.5%
Benzoic acid - 5.5%
DHA - 2.5% Lactic acid - 5%
9.2 MIO5000 MIO5000 2000 MIO5000 2500 Phenoxyethanol -
17%
Lauryl alcohol - 10%
Propylen Glycol - 60%
Benzoic acid - 5.5%
DHA - 3% Lactic acid - 5%
9.3 4000 4000 4000 2000 2000 1-Phenylpropanol
- 17%
Phenylethanol - 15%
Propylen Glycol - 54.5%
Benzoic acid - 5.5% DHA - 2.5% Lactic acid - 5%
9.4 MIO3000 MIO6000 2500 3000 MIO4000 1-Phenylpropanol -
17%
Lauryl alcohol - 10% Propylen Glycol - 60% DHA - 3%
Benzoic acid - 5.5% Lactic acid - 5%
5.1 4000 5000 4000 3000 2000 2-Phenylpropanol -
17%
Phenylethanol - 15% Propylene Glycol - 54.5%
Benzoic acid - 5.5%
DHA - 2.5% Lactic acid - 5%
5.2 MIO4000 MIO8000 MIO4000 MIO6000 MIO5000 2- Phenylpropanol
- 17%
Lauryl alcohol - 10%
Propylene Glycol - 60%
It can be concluded from the results that:
1. The anti-micro-organic activities of 1 -Phenylpropanol, 2-Phenylpropanol and 3- Phenylpropanol are better than the Phenoxyethanol one.
2. 3 -Phenylpropanol has a better activity than 1 -Phenylpropanol and 2-Phenylpropanol.
3. Blends having the same composition - except for the presence in the same amount of one of the Phenylpropanols or Phenoxyethanol showed best results with 3 -Phenylpropanol.
4. The preservative line (Formulae 17, 17.1, and 17.2) is a broad spectrum, effective against Gram -, Gram +, yeast and molds.
EXAMPLE 3
PRESERVATIVE EFFECTIVENESS (CHALLENGE TESTS)
In exemplary procedures, a sample of a face cream was tested with a preservation
comprising 1% of formula 17.1 as detailed above (in pH 5.6).
Method In exemplary procedures, the method applied was based on the USP 30 guidelines for antimicrobial effectiveness testing. The microorganisms used for the test are listed in the Table 14 below. Five samples of the product are inoculated with 1 microorganism each. The volume of the culture is calculated to yield a count of 105 - 106 CFU/g.
In exemplary procedures, a four weeks follow-up was performed. Each product was sampled once a week and a viable count was performed. In exemplary procedures, Polysorbate 20 and Soya Lecithin were added to the culture media in order to neutralize the preservatives and enable the recovery of all living microorganisms.
Table 14
Figure imgf000040_0001
In additional exemplary procedures, a sample of face cream was tested with a 0.8% preservation formulal7.2 at pH 5.58.
Method
The method applied was based on the USP 30 guidelines for antimicrobial effectiveness testing. The microorganisms used for the test were listed in the Table 15 below. Five samples of the product are inoculated with 1 microorganism each. The volume of the culture is calculated to yield a count of 105 - 106 CFU/gr.
A 4 weeks follow-up is performed. Each product is sampled once a week and a viable count is performed. Polysorbate 20 and Soy Lecithin are added to the culture media in order to neutralize the preservatives and enable the recovery of all living microorganisms.
Results The results are presented in Table 15 below.
Table 15
Figure imgf000041_0001
It can be concluded that the sampled product meets the USP criteria for category 1 products.
EXAMPLE 4
STABILITY
In exemplary procedures, the blends, being solutions of organic acids in organic solvents, were verified regarding their physical stability and particularly their resistance to crystallization according to the temperature, during storage and shipping.
All blends described below are crystallizing when exposed to a temperature neighboring +5°C. However, it was verified (Table 16 below which presents physical stability at +10 °C) that when exposed to a prolonged period of time at +10°C, most of formulation show a good thermal stability.
Table 16
Crystallization at
Code Composition ( ) Time (days)
+10°C
Benzoic a. -5.5
DHA-2.5
Formula 1.7 SLL-1 No 106
3-Phenylpropanol-17
Propylene Glycol -74 Benzoic a.-5.5
DHA-2.5
Lactic a. -5
Formula 1.71
3- Phenylpropanol-17 Yes 70
Lauryl alcohol-10
Propylene Glycol -60
Benzoic a.-5.5
DHA-3
Lactic a.-5
Formula 1.72 No
3-Phenylpropanol-17 140
Phenylethanol- 15
Propylene Glycol -54.5
Benzoic a.-5.5
DHA-3
Lactic a. -5
9.1 No 136
Phenoxyethanol- 17
Phenylethanol- 15
Propylene Glycol -54.5
Benzoic a.-5.5
DHA-2.5
Lactic a. -5
9.2 No 136
Phenoxyethanol- 17
Lauryl alcohol-10
Propylene Glycol -60
Benzoic a.-5.5
DHA-3
9.3 Lactic a.-5 Yes 32 l-Phenylpropanol-17
Phenylethanol-15
Propylene Glycol -54.5
Benzoic a.-5.5
DHA-2.5
9.4 Lactic a.-5 Yes 25
1- Phenylpropanol-17
Lauryl alcohol-10
Propylene Glycol -60
Benzoic a.-5.5
DHA-3
5.1 Lactic a.-5 No 115
2-Pheny lpropanol- 17
Phenylethanol- 15
Propylene Glycol -54.5 Benzoic a. -5.5
DHA-2.5
5.2 Lactic a. -5 Yes 6
2- Phenylpropanol-17
Lauryl alcohol- 10
Propylene Glycol -60
Taken together it can be concluded that the disclosed blends are an ideal preservative solution for the wet wipes market. They display a broad spectrum anti-micro-organic activity, are physically stable and suitable for mass market production at a competitive price.
It is to note that the data included in this report reflects the tested sample only and that any change in the product's composition and/or properties may affect the performance of the preservation system.
Although the invention has been described in conjunction with specific embodiments thereof, it is evident that many alternatives, modifications and variations will be apparent to those skilled in the art. Accordingly, it is intended to embrace all such alternatives, modifications and variations that fall within the spirit and broad scope of the appended claims.
All publications, patents and patent applications mentioned in this specification are herein incorporated in their entirety by reference into the specification, to the same extent as if each individual publication, patent or patent application was specifically and individually indicated to be incorporated herein by reference. In addition, citation or identification of any reference in this application shall not be construed as an admission that such reference is available as prior art to the present invention. To the extent that section headings are used, they should not be construed as necessarily limiting.

Claims

WHAT IS CLAIMED IS:
1. A personal care formulation comprising:
(a) 3-phenyl propanol at a concentration that ranges from 2% to 30% by volume;
(b) at least one organic acid selected from the group consisting of: dehydroacetic acid (DHA), benzoic acid, and a combination thereof;
(c) a diol and/or triol, said diol is selected from the group consisting of: 1,2-diol, 1,3-diol, and any combination thereof; and
(d) at least one emulsifier and/or alpha-dehydroxy acid.
2. The personal care formulation of claim 1, wherein said alpha-dehydroxy acid is selected from the group consisting of: lactic acid and citric acid, and combination thereof.
3. The personal care formulation of claim 1 , comprising a combination of DHA and benzoic acid.
4. The personal care formulation of claim 1, comprising:
(a) 3-phenyl propanol at a concentration that ranges from 2% to 30% by volume;
(b) DHA at a concentration that ranges from 0.1% to 5% by volume, and benzoic acid at a concentration that ranges from about 0.1% to 7 % by volume;
(c) diol and/or triol in a concentration of up to 90 % by volume; and
(e) at least one emulsifier and/or lactic acid in concentration that ranges from 0.1% to 10 % by volume.
5. The personal care formulation of claim 1, wherein said 1,2 diol is propylene glycol.
6. The personal care formulation of claim 1, wherein said 1,3 diol is selected from the group consisting of: 1,3-butanediol, and 1, 3-propandiol.
7. The personal care formulation of claim 1, wherein said triol is glycerol.
8. The personal care formulation of claim 1, wherein said at least one emulsifier is selected from the group consisting of: 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, polyethoxylated fatty acids, polyethylene glycol glycerol fatty acid esters, alcohol-oil transesterification products, polyglycerized fatty acids, propylene glycol fatty acid esters, mono-and diglycerides, sterol and sterol derivatives, polyethylene glycol sorbitan fatty acid esters, polyethylene glycol alkyl ethers, sugar esters, polyethylene glycol alkyl phenols, polyoxyethylene-polyoxypropylene block copolymers, sorbitan fatty acid esters, low alcohol fatty acid esters, ionic surfactants, and mixtures thereof; and any combination thereof.
9. The personal care formulation of claim 8, wherein said at least one emulsifier is SLL.
10. The personal care formulation of claim 9, further comprising citric acid at a concentration up to 2%, by volume.
11. The personal care formulation of claim 1 , further comprising sorbic acid, at a concentration that ranges from about 1.5 % to about 5 % by volume.
12. The personal care formulation of claim 1, further comprising at least one type of aliphatic alcohol at a concentration that ranges from 1 % to 15 % by volume, said aliphatic alcohol having at least 10 carbon atoms in its backbone chain
13. The personal care formulation of claim 12, wherein said aliphatic alcohol is lauryl alcohol.
14. The personal care formulation of claim 1, wherein said (d) is lactic acid.
15. The personal care formulation of claim 14, characterized by resistance to discoloration in an atmospheric environment.
16. An article comprising the personal care formulation of any one of claims 1-15.
17. The article of claim 16, wherein said 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.
18. The article of claim 17, wherein said personal care formulation is in the form selected from the group consisting of: paste, cream, lotion, foam, gel, emulsion, an ointment, and soap.
19. The personal care formulation of claim 1, for pharmaceutical, cosmetic and/or cosmeceutical use.
20. 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 personal care formulation of any one of claims 1- 16.
21. The method of claim 20, wherein said microorganism is selected from bacteria, molds and fungi.
22. The method of claim 21, wherein said 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; and said fungi are selected from the group consisting of: Candida albicans; and said mold is Aspergillus niger.
23. A process of preparing the personal care composition of any one of claims 1-15, the process comprising subjecting a mixture of:
(a) 3-phenyl propanol;
(b) at least one organic acid selected from the group consisting of: (DHA) and benzoic acid, and any combination thereof;
(c) a diol and/or triol; and
(d) at least one emulsifier and/or lactic acid,
to temperature that ranges from about 10 °C to about 60 °C while stirring, for a time duration that ranges from about 30 min to about 2 hours.
PCT/IL2015/051141 2014-11-25 2015-11-24 Antimicrobial preservative compositions WO2016084078A1 (en)

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US20190124921A1 (en) * 2017-10-30 2019-05-02 Troy Corporation Antimicrobial organic preservatives
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WO2023229810A1 (en) * 2022-05-24 2023-11-30 Microban Products Company Compositions and methods for microbial control in polymers

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