GB2597440A - Skincare formulation - Google Patents

Skincare formulation Download PDF

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Publication number
GB2597440A
GB2597440A GB2009215.1A GB202009215A GB2597440A GB 2597440 A GB2597440 A GB 2597440A GB 202009215 A GB202009215 A GB 202009215A GB 2597440 A GB2597440 A GB 2597440A
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United Kingdom
Prior art keywords
formulation
antimicrobial
benzalkonium
water
agent
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GB2009215.1A
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GB202009215D0 (en
Inventor
Stevens Martin
Bullimore Mark
Lancucka Anna
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Creightons PLC
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Creightons PLC
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Priority to GB2009215.1A priority Critical patent/GB2597440A/en
Publication of GB202009215D0 publication Critical patent/GB202009215D0/en
Priority to PCT/GB2021/051534 priority patent/WO2021255457A1/en
Publication of GB2597440A publication Critical patent/GB2597440A/en
Pending legal-status Critical Current

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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/13Amines
    • A61K31/14Quaternary ammonium compounds, e.g. edrophonium, choline
    • 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
    • A61K8/04Dispersions; Emulsions
    • A61K8/06Emulsions
    • A61K8/062Oil-in-water emulsions
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/08Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
    • A61K47/10Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/24Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing atoms other than carbon, hydrogen, oxygen, halogen, nitrogen or sulfur, e.g. cyclomethicone or phospholipids
    • 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
    • A61K8/04Dispersions; Emulsions
    • A61K8/06Emulsions
    • 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
    • A61K8/31Hydrocarbons
    • 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
    • A61K8/37Esters of carboxylic acids
    • 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
    • A61K8/40Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing nitrogen
    • A61K8/41Amines
    • A61K8/416Quaternary ammonium compounds
    • 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
    • A61K8/72Cosmetics or similar toiletry preparations characterised by the composition containing organic macromolecular compounds
    • A61K8/81Cosmetics or similar toiletry preparations characterised by the composition containing organic macromolecular compounds obtained by reactions involving only carbon-to-carbon unsaturated bonds
    • A61K8/817Compositions of homopolymers or copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and at least one being terminated by a single or double bond to nitrogen or by a heterocyclic ring containing nitrogen; Compositions or derivatives of such polymers, e.g. vinylimidazol, vinylcaprolactame, allylamines (Polyquaternium 6)
    • 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
    • A61K8/72Cosmetics or similar toiletry preparations characterised by the composition containing organic macromolecular compounds
    • A61K8/84Cosmetics or similar toiletry preparations characterised by the composition containing organic macromolecular compounds obtained by reactions otherwise than those involving only carbon-carbon unsaturated bonds
    • A61K8/89Polysiloxanes
    • A61K8/891Polysiloxanes saturated, e.g. dimethicone, phenyl trimethicone, C24-C28 methicone or stearyl dimethicone
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/04Antibacterial agents
    • 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

Abstract

A formulation comprising a benzalkonium antimicrobial agent, a cationic emulsifier, one or more moisturising agents, and water. The formulation may be an oil-in-water emulsion (O/W). The cationic emulsifier may be a quaternary ammonium compound of formula: Where R1 is a C12-26 alkyl, R2 is a C1-3 alkyl, C12-26 alkyl, or a C12-26 carboxamide group, R3 and R4 are C-13 alkyl, and X is a pharmacologically acceptable salt anion. The cationic emuslfier may be distearyldimonium, behentrimonium, or palmitamidopropyltrimonium halides. The antimicrobial agent may be benzalkonium halide. The moisturing agent may include an occlusive agent selected from petrolatum, lanolin, mineral oil, polysiloxane, may include a fatty acid emollient, may include a humectant selected from glycerol (glycerine, glycerin), sorbitol, urea, sodium lactate, propylene glycol, polethylene glycol (PEG), hyaluronic acid, and it may comprise an emollient, occlusive agent, and a humentant, which may be isopropyl palmite, petrolatum, and glycerol. The formulation may comprise benzalkonium chloride and distearyldimonium chloride. A preparation method is provided, wherein the cationic emuslifer and moisturising agent(s) are heated to form a lipohilic mixture, added to a spearate heated volume of water, cooled to 40 C or less, and the benzalkonium is added, followed by pH adjustment to pH 3.5-4.5

Description

Skincare Formulation This invention relates to a topical formulation for skincarc and in particular to a topical formulation (eg a cosmetic formulation) having moisturising and antimicrobial properties.
One of the most effective ways to prevent illness and limit the spread of bacterial, viral and fungal infections is through frequent hand cleaning. In certain settings including hospitals, care homes, restaurants, schools and food production sites it is essential that staff and visitors maintain hygiene levels. Staff must therefore wash or disinfect their hands many times every day. Although effective at killing and removing most bacteria and viruses, frequent washing with soap results in dry skin Over time hands may become sore and cracked. Cracked or wounded skin can increase the risk of infection and make washing painful.
Most commercially available antibacterial hand sanitisers are alcohol based, containing a high weight percentage of alcohols such as isopropanol, ethanol or n-propanol as the active antimicrobial agent. These alcohols exhibit antimicrobial activity by adjusting polarity around lipid layers in viruses and bacteria, disrupting the self-assembly of these structural layers leading to the destruction of the organism. However, similar lipids are also present in and around skin cells where they have important structural and moisture retention 5 properties. Alcohol sanitizers can also break down and remove these lipids. Repeated exposure to alcohol sanitizers results in dry, cracked and sore skin. Some sanitizer products contain moisturising agents to counteract the drying effect. However, in order to be effective as antimicrobials hand sanitizers require a very high alcohol content (typically greater than 70 wt.%). By comparison, moisturising agents typically make up less than 1% of the formulation. These formulations are therefore still dominated by the activity of the alcohol and the effectiveness of the moisturising agents is limited.
Moisturising creams and lotions are available to counteract the drying effects of frequent hand washing or use of alcohol-based sanitizers. These are most commonly oil in water emulsions. The oily components of these products may act as occlusive agents to prevent or limit moisture loss from the skin. They may also act as emollients, replacing the natural lipids present in skin sebum which may be lost through persistent washing or use of alcohol sanitisers. Typical oily components include mineral oil and petrolatum. Petrolatum is notoriously difficult to formulate into a cosmetically acceptable form as it can feel greasy. Conventional non-ionic and anionic emulsifiers also reduce the effectiveness of petrolatum as a moisturising agent.
Cationic emulsifiers such as quaternary ammonium compounds have been shown to mask the negative "greasy" feel of a high oil load, giving the skin a powdery, smooth feel.
US4389418 discloses a skin care composition containing petrolatum in combination with a quaternary ammonium emulsifier, a fatty alcohol stabiliser and a fatty ester as another emollient. However these moisturising formulations contain no active antimicrobial agents, meaning that users must separately clean and moisturise their hands. Conventional antimicrobial agents disrupt the stability of the emulsions resulting in reduced shelf life. 30 Typically, a relatively large amount of conventional antimicrobial agents is required for a formulation to be an effective biocide. These high concentrations disrupt the stability of the emulsion, reduce the effectiveness of the moisturising components and decrease the shelf life of cosmetic products.
The present invention seeks to provide a topical formulation containing both moisturising agents and antimicrobial agents which is capable of providing long-lasting moisturisation and biocidal action whilst having cosmetically acceptable tactile properties.
Viewed from a first aspect the present invention provides a topical antimicrobial formulation comprising: a benzalkonium antimicrobial agent; a cationic emulsifier; one or more moisturising agents; and water.
The present invention does not rely on volatile alcohol-based antimicrobial agents such as ethanol but instead uses a benzalkonium based antimicrobial agent. This is capable of 15 persisting on the skin for a longer time period after application and therefore requiring much lower loading of antimicrobial agents in the formulation.
Preferably the formulation is free from CI to CO alcohols (eg CI to CO alkanols). Particularly preferably the formulation is free from ethanol, isopropanol or n-propanol. The 20 absence of these volatile alcohols may also reduce damage to natural lipids in skin sebum, helping to prevent the "drying" effect experienced with alcohol-based sanitisers.
Lower alcohol levels may also facilitate the formation of stable emulsions which widens the range of moisturising agents usable in the formulation and enables moisturising agents 25 to be included at levels sufficient to provide long-lasting moisturisation of the skin.
In the context of this specification, "long-lasting moisturisation" may be interpreted to mean that after application to skin, the formulation may provide a moisturising effect for around one hour or more after application, for example between one hour and eight hours after application, and that moisturising agents may be at least partially resistant to removal by washing. "Cosmetically acceptable tactile properties" may be interpreted to mean that the formulation has an acceptable consistency, feel and lubricity, may be absorbed rapidly by the skin and may dry quickly.
The formulation may be composed as a lotion or a cream. Preferably the formulation is an 5 oil-in-water or a water-in-oil emulsion. More preferably the formulation is an oil-in-water emulsion and the cationic emulsifier is a cationic oil-in-water emulsifier.
Cationic emulsifiers may effectively reduce the oily or greasy feel caused by high lipophilic content of moisturisers and may impart a powdery and smooth feel compared to conventional non-ionic and anionic emulsifiers. Anionic emulsifiers may also degrade the cationic antimicrobial agent or reduce its activity. Cationic emulsifiers are advantageously compatible with the cationic benzalkonium antimicrobial agent. The combination of cationic emulsifiers and benzalkonium cations may also have a synergistic effect: the surfactant properties of the benzalkonium may contribute to the formation of stable emulsions; and the cationic emulsifier may stabilise the benzalkonium in the emulsion, and may prevent separation or degradation of the antimicrobial agent.
The cationic emulsifier may be a dialkyl, monoalky or amidoquat type quaternary ammonium compound. Preferably the cationic emulsifier is a quaternary ammonium 20 compound of formula: R1 N-wherein Ri is an alkyl group having between 12 and 26 carbon atoms; 122 is selected from a group consisting of an alkyl group having between 12 and 26 carbon atoms, an alkyl group having between 1 and 3 carbon atoms and a carboxamide group having between 12 and 26 carbon atoms; R3 and R4 are alkyl groups having between 1 and 3 carbon atoms and X is a first pharmacologically acceptable salt forming anion.
Preferably the first pharmacologically acceptable salt forming anion is a halide (eg chloride).
Preferably the cationic oil emulsifier is selected from a group consisting of a distearyldimonium halide, a behentrimonium halide, and a palmitamidopropyltrimonium 5 halide. The positive charge of the quaternary ammonium may improve adsorption onto negatively charged surfaces such as hair and skin. This may result in a soft, matte and smooth feeling to skin and may help to reduce any static effects of charged skin and hairs The ammonium cations may also reduce irritation caused by residual soap or detergent present on the skin surface. Soap and detergent molecules are usually negatively charged 10 and may be effectively complexed by the cationic emulsifier.
Preferably the benzalkonium antimicrobial agent comprises benzalkonium cations and a second pharmacologically acceptable salt forming anion. Preferably the benzalkonium antimicrobial agent comprises a benzalkonium cation of the following formula:
CH
CnH2rol CH3 where n is an integer in the range 8 to 18. In certain embodiments an additional substituent (not shown) may be present on the benzene ring. Preferably the additional substituent is a short chain alkyl group or a Schiff base.
The second pharmacologically acceptable salt forming anion may be a monatomic or polyatornic singly charged salt forming anion suitable for application to cosmetics, including halides (fluoride, chloride, bromide and iodide), saccharinate, or acetate, or anions of amino acids such as valinate, tryptophanate, tyrosinate, isoleucinate, leucinate, histidinate or prolinate. Preferably the second pharmacologically acceptable salt forming anion is a halide and the benzalkonium antimicrobial agent is a benzalkonium halide. Particularly preferably the second pharmacologically acceptable salt forming anion is chloride and the benzalkonium antimicrobial agent is benzalkonium chloride.
The hydrophobic alkyl chain of the bentalkonium can interact with lipid membranes of bacteria and viruses and leads to the perturbation and disruption of membrane bilayers. The proximity of the charged quaternary ammonium centre may also disrupt the charge distribution of the membrane, leading ultimately to the membrane breaking down thereby destroying the organism. The comparative low volatility of benzalkonium antimicrobial agents means that a lower quantity of antimicrobial agent may be required in the formulation to achieve longer-lasting antimicrobial effects compared to alcohol-based formulations.
The one or more moisturising agents may include an occlusive agent. Occlusive agents act as barriers on the surface of skin to prevent moisture loss. Any lipophilic occlusive agent suitable for use in cosmetics may be used and may be derived from hydrocarbons and/or plant or animal sources. Preferably the occlusive agent is selected from a group consisting of petrolatum, lanolin, mineral oil and polysiloxane.
Where the occlusive agent includes petrolatum, any grade of white or yellow petrolatum determined to be safe for cosmetic use may be used. The petrolatum may be mixed with other hydrocarbon materials such as mineral oil, microcrystalline wax and paraffin wax, and/or lipophilic natural plant or animal extracts.
The one or more moisturising agents may include an emollient. The emollient may he derived from natural and/or synthetic sources. The one or more moisturising agents preferably includes a fatty ester emollient. The fatty ester emollient preferably comprises one or more compounds selected from a group consisting of isopropyl paltnitate, isopropyl myristate, isopropyl isostearate, isostearyl isostearate, diisopropyl sebacate, propylene glycol dipelargonate, 2-ethyl-hexyl stearate, isopropyl lanolate, 2-ethyl-hexyl salicylate, 2-ethylhexyl isononoate and a fatty alcohol lactate.
The one or more moisturising agents may include a humectant selected from a group consisting of glycerol, sorbitol, urea, sodium lactate, propylene glycol, polyethylene glycol and hyaluronic acid Preferably die formulation comprises an emollient, an occlusive agent and a humectant. Particularly preferably the moisturising agents comprise petrolatum, isopropyl palmitate and glycerol.
Preferably the cationic emulsifier is a quaternary ammonium emulsifier and the benzalkonium antimicrobial agent is a benzalkonium halide. Particularly preferably the benzalkonium antimicrobial agent is benzalkonium chloride and the cationic emulsifier is distearyldimonium chloride. Most preferably the benzalkonium antimicrobial agent is benzalkonium chloride, the cationic emulsifier is distearyldimonium chloride and the moisturising agents are petrolatum, isopropyl palmitatc and glycerol.
The benzalkonium antimicrobial agent may be between 0 % and 3 % of the formulation by weight. Preferably the benzalkonium antimicrobial agent is 1 % or less of the formulation by weight. Even more preferably the benzalkonium antimicrobial agent is between 0.01 % 20 and 0.1 % of the formulation by weight.
The cationic emulsifier may be between 2 % and 8 % of the formulation by weight. Preferably the cationic emulsifier is between 3 % and 5 % of the formulation by weight.
The one or more moisturising agents may be between 5 % and 25 % of the formulation by weight. Preferably the moisturising agents be between 1()% and 18 % of the formulation by weight. Where the one or more moisturising agents includes an occlusive agent, the occlusive agent preferably is between 3 % and 5 % of the formulation by weight. Where the one or more moisturising agents includes an emollient, the emollient preferably is between 3 % and 5 % of the formulation by weight. Where the one or more moisturising agents includes a humectant, the humectant preferably is between 4 % and 8 % of the formulation by weight.
The amount of water in the formulation varies according to the required consistency of the formulation. For example a lotion will typically require a higher water content than a cream. If a lotion is required, the water content of the formulation is preferably 50 % or greater by weight. More preferably the water content of the formulation is between 60 % and 80 % by weight. If a cream is required, the water content is preferably between 25 % and 50 % of the formulation by weight.
Preferably the benzalkonium antimicrobial agent is less than 1 % of the formulation by I() weight; the cationic emulsifier is between 2 % and 8 % of the formulation by weight; the moisturising agents are between 5 % and 25 % of the formulation by weight; and the water is between 60 % and 80 % of the formulation by weight.
Although the benzalkonium antimicrobial agent may itself assist with stabilisation of the emulsion, the formulation may further comprise an emulsion stabiliser. The emulsion stabiliser stabilises the emulsion and can also act as a viscosity modifier to provide a formulation of the required viscosity. Preferably the emulsion stabiliser is a fatty alcohol such as stearyl alcohol, cetyl alcohol, tetradecanol, docosanol, arachidyl alcohol, isostearyl alcohol or isocetyl alcohol. Particularly preferably the emulsion stabiliser is cetyl alcohol.
Fatty alcohols may also provide an °pacifying effect to the formulation.
The emulsion stabiliser may be between 1 % and 10 % of the formulation by weight. Preferably the emulsion stabiliser is between 3 % and 5 % of the formulation by weight.
The formulation may further comprise a fatty alcohol ethoxylate, preferably a C16-18 fatty alcohol ethoxylate such as Ceteareth-20. The fatty acid ethoxylate may also act as an emulsion stabiliser, as well as an °pacifying agent and a viscosity modifier. The fatty alcohol ethoxylate may be between 0.1 % and 2 % of the formulation by weight. Preferably the fatty alcohol ethoxylate is between 0.1 % and 0.6 % of the formulation by weight The formulation may further comprise a lubricant or lubricity modifier to adjust the lubricity of the formulation to optimise the feeling and ease of application of the formulation in use. Any aqueous, oil based or polysiloxane (silicone) based lubricant regarded as safe for use in cosmetic formulations may be used. Preferably the lubricity modifier is a polysiloxane lubricant such as dimethicone. Polysiloxane lubricants may advantageously provide long lasting lubrication and may also help to prevent foaming of lotions and creams.
The lubricity modifier may be between 0.1 % and 5 % of the formulation by weight.
Preferably the lubricity modifier is between 0.5 % and 2 % of the formulation by weight.
The formulation may further comprise a thickener. Preferably the thickener is a polyquaternium thickener such as Polyquatemium-37. Polyquaternium thickeners are advantageously compatible with the cationic emulsifier and antimicrobial agent.
Polyquaterniurn thickeners may also act as film-forming agents. The thickener may be between 0.01 % and 0.5 % of the formulation by weight. Preferably the thickener is between 0.01 % and 0.1 % of the formulation by weight.
The formulation may further comprise a preservative. The preservative is intended to prevent the growth of micro-organisms within the formulation and increase its shelf life. Preferably one or more preservatives are selected from a group consisting of phenoxyethanol, esters of parahydroxybenzoic acid and formaldehyde. Ethylhexylglycerin may be included with the preservative as a preservative booster.
The preservative may be between 0.1 % and 5 % of the formulation by weight. Preferably the preservative is between 0.5 % and 2 % of the formulation by weight.
The formulation may further comprise additional cosmetic additives such as fragrances and dyes. The additional cosmetic additives are preferably less than 1 % of the formulation by 30 weight.
The formulation may further comprise a pH modifier such as an organic acid. The pH modifier is preferably citric acid. Preferably the pH modifier is between 0.01 % and 0.1 % of the formulation by weight.
The formulation may further comprise one or more active sun-screening agents such as para-aminobenzoic acid, cinoxate, dioxybenzone, oxybenzone, titanium dioxide or zinc oxide. This gives the formulation the additional function of providing protection to the skin against UVA and/or UVB radiation. Preferably the active sun-screening agents are less than 8 % of the formulation by weight.
Viewed from a second aspect the present invention provides a method for preparing an antimicrobial skincare formulation, comprising: combining a cationic emulsifier and one or more moisturising agents and heating to a temperature sufficient for each to melt and combine to form a lipophilic mixture; heating a separate volume of water to substantially the same temperature; adding the heated lipophilic mixture to the heated water to form an emulsion; allowing the emulsion to cool to a temperature of 40 °C or less; adding a benzalkonium antimicrobial agent to the emulsion; and adding a pH modifier to adjust the pH of the emulsion to between 4 and 5.
Preferably the water is deionised or distilled water.
Preferably the pH modifier is added to adjust the p1-1 of the emulsion to between 3.5 and 4.5.
The method may further comprise filtering the emulsion after adding the pH modifier to remove any residual solid components. Preferably the emulsion is cooled to a temperature of less than 35 °C before filtration. Preferably the emulsion is filtered using a 300-micron filter.
The method may further comprise adding an emulsion stabiliser to the lipophilic mixture before the heated lipophilic mixture is added to the heated water.
The method may further comprise adding a lubricity modifier to the lipophilic mixture before the heated lipophilic mixture is added to the heated water.
The method may further comprise adding a fatty alcohol ethoxylate to the lipophilic 5 mixture before the heated lipophilic mixture is added to the heated water.
The method may further comprise adding a humectant to the water before the lipophilic mixture is added to the water.
The method may further comprise adding a thickener to the water before the lipophilic mixture is added to the water.
The temperature is preferably between 60 °C and 100 °C, or more preferably between 75 °C and 85 'C.
The method may further comprise allowing the emulsion to cool to a temperature of 50 °C or less and then adding a preservative, before cooling to 40 'V or less and adding the benzalkonium antimicrobial agent.
Example
The invention will now be described by reference to a specific Example. The Example is not to be considered as limiting the scope of the present invention.
All components used in example formulations can be obtained commercially and should be of a chemical purity grade recognised as safe for use in cosmetic products, such as U.S.P. 30 grade, N.F. grade or higher.
A formulation 10 suitable for use as a lotion for skincare was prepared as follows: Distearyldimonium chloride, petrolatum, isopropyl palmitate, cetyl alcohol, ceteareth-20 and dimethicone were added to a suitable vessel and heated to a temperature of 80 °C with stirring to ensure that the petrolatum was fully molten and no lumps remained. The resulting molten lipophilic mixture was maintained at 80 °C ± 2 °C until further required.
Deionised water was added to a separate vessel and heated to a temperature of 80 °C with stirring. During healing, glycerol was added to the deionised water with stirring. After adding glycerol, polyquatemium-37 was added to the mixture with further stirring. The resultant hydrophilic mixture was mixed until uniform and was maintained at 80 'C ± 2 °C.
The molten lipophilic mixture was then added to the heated hydrophilic mixture with constant stirring, maintaining the temperature at 80 ± 2 'C. The combined phases were then stirred vigorously for 10 minutes at a temperature of 80 'V ± 2 °C until the bulk mixture was smooth and uniform.
The mixture was then cooled gradually to a temperature of 35 'C whilst stirring slowly. When the temperature of the bulk mixture was in the range 45 -50 °C, a mixture of 90 wt.% phenoxyethanol and 10 wt.% ethylhexylglycerin was added to the bulk mixture with stirring.
When the temperature of the bulk mixture was below 40 °C, benzalkonium solution (50 wt.% in water) was added with stirring until the bulk mixture was smooth and uniform.
Citric acid was then added to the bulk mixture with stirring to adjust the pH to between 3.5 and 4.5.
Once the temperature of the bulk mixture was below 35 'C., it was passed through a 300-micron filter to remove solid particles. The composition of the resulting formulation 10 is 30 shown in Table 1.
Table 1: Composition of Formulation 10 Component Weight percent Glycerol 5.00 Distearyldimonium chloride 4.75 Petrolatum 4.50 Isopropyl palmitate 4.50 Cetyl alcohol 3.75 Dimethicone 1.00 Phenoxyethanol 0.90 Citric acid 0.07 Benzalkonium chloride 0.10 Ethylhexylglycerin 0.10 Polyquatern iu m-37 0.10 Ceteareth-20 0.50 Deionised water 74.73 The primary moisturising and conditioning agents in the formulation 10 are petrolatum, isopropyl palmitate and glycerol. Petrolatum acts as an occlusive agent, whereas 5 isopropyl palmitate is an emollient. The hydrophilic glycerol acts as a humectant.
Distearyldimonium chloride is a quaternary ammonium cationic surfactant which acts as a cationic emulsifier in the formulation 10.
Dimethicone is an organosilicon lubricant used to improve feeling and ease of application oldie formulation to the skin. It may also provide secondary effects as an emulsifier and emulsion stabiliser due to its surfactant properties. Cetyl alcohol also functions as an emulsion stabiliser, as well as an °pacifying agent and a viscosity modifier.
Phenoxyethanol functions primarily as a preservative. Ethylhexylglycerin acts as a preservative booster. Polyquatemium-37 acts as a thickener and film-forming agent. Ceteareth-20 acts as an emulsion stabiliser, an °pacifying agent and a viscosity modifier.
No additional colourants or perfumes were added to the formulation 10.
The active antimicrobial component of the formulation 10 is benzalkonium chloride. The benzalkonium cation has a positively charged quaternary ammonium centre and a 5 hydrophobic alkyl chain with a length of between 8 and 18 carbon atoms.
The bactericidal activity of the formulation 10 was tested according to the BS EN 1276:2019 suspension test protocol. The formulation 10 was diluted with distilled water to give two samples with concentrations of 50% and 0.1% (v/v formulation in water). A third sample of the undiluted formulation was also tested. A suspension of target bacteria in clean 0.1 g/1 bovine albumin was then added to each of the samples. The samples were maintained at 20 °C (± 1°C) for 2 minutes (± 10 seconds), an aliquot of each sample was then taken, the bactericidal/bacteriostatic activity was immediately neutralised and the numbers of surviving bacteria in each sample were determined. This test was performed on four target bacteria: Pseudomonas aeruginosa, Staphylococcus aureus, Enterococcus hirae and Escherichia coll. The results of the test are summarised in Table 2.
Table 2: Results of bactericidal activity tests of the formulation 10 Test organism No Undiluted sample 50% (v/v) sample 0.10% (v/v) sample Na R Na R Na R Pseudomonas aeruginosa 7.34 < 2.15 > 5.19 < 2.15 > 5.19 > 7.52 < -0.18 Escherichia coli 7.48 < 2.15 > 5.33 < 2.15 > 5.33 > 7.52 < -0.04 Staphylococcus aureus 7.19 <2.15 > 5.04 <2.15 > 5.04 6.96 0.23 Enterococcus hirae 7.46 <2.15 > 5.31 <2.15 > 5.31 >7.52 <-0.06 In Table 2, No is the logarithm (base 10) of the number of colony-forming units (cfu) per millilitre of the sample at the start of the contact time. Na is the logarithm (base 10) of the number of colony-forming units (cfu) per millilitre surviving in the sample after the two minute exposure time. R corresponds to the reduction in viable bacterial counts and is calculated according to the following equation: R = No -Na Acceptable bactericidal activity is defined as an R value of 5 or greater, corresponding to a 5-log (99.999%) reduction in living bacterth. As shown in Table 2, the formulation 10 achieves R values greater than 5 for all bacteria tested when undiluted and at a 50% dilution. This indicates that the formula 10 is effective as an antibacterial hand lotion.

Claims (15)

  1. Claims 1. A topical antimicrobial formulation comprising: a benzalkoniurn antimicrobial agent; a cationic emulsifier; one or more moisturising agents; and water.
  2. 2. The topical antimicrobial formulation of claim I, wherein die formulation is an oil-in10 water emulsion and the cationic emulsifier is a cationic oil-in-water emulsifier.
  3. 3. The topical antimicrobial formulation of claim 1 or 2, wherein the cationic emulsifier is a quaternary ammonium compound of formula: R3 [ X] wherein RI is an alkyl group having between 12 and 26 carbon atoms; 122 is selected from a group consisting of an alkyl group having between 12 and 26 carbon atoms, an alkyl group having between I and 3 carbon atoms and a carboxamide group having between 12 and 26 carbon atoms; R3 and R4 arc alkyl groups having between 1 and 3 carbon atoms and X is a first pharmacologically acceptable salt forming anion.
  4. 4. The antimicrobial skincare formulation of claim 3, wherein the cationic emulsifier is selected from a group consisting of a distearyldimonium halide, a behentrimonium halide, and a palmitamidopropyltrimonium
  5. 5. The antimicrobial skincare formulation of any preceding claim, wherein the benzalkonium antimicrobial agent is a benzalkonium
  6. 6. The antimicrobial skincare formulation of any preceding claim, wherein the one or more moisturising agents includes an occlusive agent selected from a group consisting of petrolatum, lanolin, mineral oil and polysiloxane.
  7. 7. The antimicrobial skincare formulation of any preceding claim, wherein the one or more 10 moisturising agents includes a fatty ester emollient.
  8. 8. The antimicrobial skincare formulation of any preceding claim, wherein the one or more moisturising agents includes a humectant selected from a group consisting of glycerol, sorbitol, urea, sodium lactate, propylene glycol, polyethylene glycol and hyaluronic acid.
  9. 9. The antimicrobial skincare formulation of any preceding claim, wherein the one or more moisturising agents comprises an emollient, an occlusive agent and a humectant.
  10. 10. The antimicrobial skincare formulation of claim 9, wherein the emollient is isopropyl 20 palmitate the occlusive agent is petrolatum and the humectant is glycerol.
  11. 11. The antimicrobial skincare formulation of any preceding claim, wherein the cationic emulsifier is distearyldimonium chloride and the benzalkonium antimicrobial agent is benzalkonium chloride.
  12. 12. The antimicrobial skincare formulation of any preceding claim, wherein the benzalkonium antimicrobial agent is less than 1 % of the formulation by weight; the cationic emulsifier is between 2 % and 8 % of the formulation by weight; the moisturising agents are between 5 % and 25 % of the formulation by weight and the water is between 60 % and 80 % of the formulation by weight.
  13. 13. A method for preparing an antimicrobial skincare formulation comprising: combining a cationic emulsifier and one or more moisturising agents and heating to a temperature sufficient for them to melt and combine to form a lipophilic mixture; heating a separate volume of water to substantially the same temperature; adding the heated lipophilic mixture to the heated water to form an emulsion; allowing the emulsion to cool to a temperature of 40 °C or less; adding a benzalkonium antimicrobial agent to the emulsion; and adding a pH modifier to adjust the pH of the emulsion to between 3.5 and 4.5.
  14. 14. The method of claim 13, further comprising cooling the emulsion to a temperature of 35 °C or less and then filtering the emulsion after adding the pH modifier.
  15. 15. The method of claim 13 or 14, further comprising adding a humectant to the water before the heated lipophilic mixture is added to the heated water.
GB2009215.1A 2020-06-17 2020-06-17 Skincare formulation Pending GB2597440A (en)

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