Use of UV filters for treating acne
The potential for sunscreens to exacerbate acne is addressed by applying a UV filter composition containing free octocrylene, ethylhexyl salicylate, and butylmethoxydibenzoylmethane to the skin and exposing it to UV radiation. problem, achieving the effects of reducing the abundance of Propionibacterium acnes and enhancing skin barrier function.
Patent Information
- Application Number
- CN202380046784.9
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Priority Date
- 2022-06-15
- Filing Date
- 2023-06-07
- Publication Date
- 2025-01-24
AI Technical Summary
Existing sunscreens may promote or exacerbate acne, and the abundance of pathogenic Propionibacter acnes in the skin microbiome after UV radiation is increased.
Use a UV filter composition containing free octocrylene, ethylhexyl salicylate and butylmethoxydibenzoylmethane, pre-applied to the skin surface and then exposed to UV radiation to reduce Propionibacterium acnes abundance while protecting Staphylococcus epidermidis.
Effectively reduce the survival rate of acne propionia after UV radiation, and reduce the risk of acne, especially the acne progress that exacerbates the application of sunscreen, and enhance the surface barrier and immune function of the skin.
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Figure BDA0005185012940000181
Abstract
Description
[0001] The present invention relates to the use of selected ultraviolet (UV) filters selected from the group consisting of octocrylene, ethylhexylsalicylate and butylmethoxydibenzoylmethane for reducing the abundance of Propionibacterium acnes (C. acnes) strains in the skin microbiota after UV radiation. The use is suitable for preventing and / or treating the progression of acne, in particular the progression of acne aggravated by the application of sunscreen.
[0002] The skin is the outermost protective layer of an organism and is the largest organ in the human body. It acts as a barrier and protects the body from external factors. It is also well known that the skin surface is inhabited by a variety of microorganisms that form the skin microbiome (often also referred to as the skin microbiome). Most of these microorganisms are symbiotic organisms that live in a mutually beneficial symbiotic relationship with the skin's immune system. Dysbiosis of the skin microbiome is associated with many skin pathologies, such as acne, atopic dermatitis, and psoriasis.
[0003] Acne (a general term for acne vulgaris) is a common, chronic skin problem that affects the pilosebaceous unit of the hair follicles. It is estimated that approximately 85% of adolescents and young adults have been affected by this disease. Acne typically presents as inflamed papules, pustules, or nodules. Inflammation may also be associated with redness, swelling, and tenderness. Acne has been identified as being associated with the presence of certain opportunistic strains of the bacterium Propionibacterium acnes (C. acnes). The P. acnes population of strains is divided into six major phylotypes: IA1, IA2, IB, IC, II, and III. In patients with severe acne, phylotype IA1 is found to be predominant.
[0004] It is well known that sunscreens may promote or exacerbate acne. Furthermore, it has been shown that acne is triggered by an imbalance in the skin microbiome associated with specific types of pathogenic P. acnes strains. Therefore, regulating the population of such P. acnes strains on the skin by using specific sunscreens may be useful by applying such sunscreens on acne-prone skin to prevent the formation or worsening of acne after such use.
[0005] Therefore, there is a continuing need to reduce pathogenic P. acnes strains in the skin microbiome following sunscreen application and UV exposure.
[0006] Therefore, the inventors have developed a targeted in vitro liquid model in a 96-well microplate format to screen for UV protective active substances ("UV filters") that allow bacterial survival. The effect of the selected UV irradiation conditions tested in the presence of various UV filters and their combinations on the microbial population of Propionibacterium acnes and a commensal reference strain of Staphylococcus epidermidis was evaluated by the evolution of the residual microbial population after 4 h. The bacterial growth inhibition as a result of UV irradiation was compared with that of the same strains without UV irradiation and expressed as a percentage (%) of survival.
[0007] Surprisingly, it has now been found that certain UV filters are able to reduce the total amount of pathogenic Propionibacterium acnes after UV irradiation.
[0008] Thus, in a first embodiment, the present invention relates to a method for reducing P. acnes, said method comprising the step of applying to an external surface of a human body having a skin microbiota comprising P. acnes and / or having acne-prone skin to UV radiation an effective amount of a sunscreen composition comprising one or more UV filters selected from the group consisting of octocrylene (OC), ethylhexyl salicylate (EHS) and butyl methoxydibenzoylmethane (BMDBM).
[0009] In another embodiment, the present invention relates to the use of one or more UV filters selected from the group consisting of octocrylene, ethylhexyl salicylate and butyl methoxydibenzoylmethane for reducing the abundance of Propionibacterium acnes in the skin microbiota after UV irradiation, in particular for preventing and / or treating the progression of acne, most particularly the progression of acne exacerbated by the application of sunscreens.
[0010] In all embodiments of the present invention, preferably at the same time the survival rate of the skin commensal Staphylococcus epidermidis is also increased by applying one or more UV filters selected from the group consisting of octocrylene, ethylhexyl salicylate and butyl methoxydibenzoylmethane. Thus, in a preferred embodiment, all methods and uses disclosed herein encompass simultaneously protecting Staphylococcus epidermidis from the harmful effects of UV radiation compared to untreated controls.
[0011] All methods and uses disclosed herein are particularly suitable for treating or preventing dysbiosis and thereby strengthening the surface barrier and immune function of the skin after UV radiation. The methods and uses as disclosed herein are also suitable for promoting a healthy skin microbiome after UV radiation by enabling a reduction in the abundance of pathogenic Propionibacterium acnes strains compared to untreated controls, while increasing the abundance of Staphylococcus epidermidis.
[0012] Since the number, ie, abundance, of P. acnes is reduced after UV irradiation, the metabolites secreted by the bacteria may also be reduced.
[0013] Without wishing to be bound by theory, these metabolites are believed to contribute to the progression of acnegenic skin. Thus, in another aspect, the present invention relates to the use of a sunscreen composition comprising one or more UV filters selected from the group consisting of octocrylene, ethylhexyl salicylate and butyl methoxydibenzoylmethane for preventing or treating acne by balancing the skin microbiota after exposure of said skin microbiota to UV radiation.
[0014] In a further aspect, the present invention also relates to a method for preventing or treating acne by microbiota balance (i.e. by reducing Propionibacterium acnes and increasing Staphylococcus epidermidis compared to an untreated control), said method comprising the step of applying a sunscreen composition comprising one or more UV filters selected from the group consisting of octocrylene, ethylhexyl salicylate and butyl methoxydibenzoylmethane to the surface of a human body before UV radiation, then exposing said surface to UV radiation and optionally observing said effect. Preferably, the surface of the human body is at least one of the skin or the scalp. The method according to this aspect may be therapeutic or non-therapeutic. In an advantageous embodiment, said method is non-therapeutic, including cosmetic, i.e. intended to beautify the skin. In another advantageous embodiment, said method is therapeutic, for example for the treatment of acne.
[0015] According to the present invention, the reduction of Propionibacterium acnes, such as in particular Propionibacterium acnes ATCC 11827 (which is known to be a conditional pathogen belonging to phylotype IA) is characterized in that after exposure to 3 standard erythema doses SED (1 SED = 100 J / m2) of UV radiation, the survival rate of Propionibacterium acnes is reduced compared to the control, for example, in particular by at least -10%, preferably at least -30%, most preferably at least -60%, for example in the range of -10%, -30% or -60% to -100% or -10%, -30% or -60% to -75%.
[0016] Protection against S. epidermidis according to the invention is characterized in that after exposure to UV radiation (with 15 SED) the survival of S. epidermidis is increased by at least 20%, preferably at least 50%, such as in the range of +20 to +100% or +50 to +100% compared to a control.
[0017] Particularly preferred UV filters according to the invention are ethylhexyl salicylate and butyl methoxydibenzoylmethane, most preferably butyl methoxydibenzoylmethane, as they lead to a particularly good reduction in the survival of Propionibacterium acnes, such as in particular Propionibacterium acnes ATCC 11827.
[0018] The total amount of UV filters in the sunscreen composition depends largely on the targeted protection and the UV radiation to be exposed to. Preferably, in all embodiments of the invention, the amount of UV filters is chosen such that the sunscreen composition exhibits an SPF of at least 20, preferably at least 25, most preferably at least 30, for example in the range of 20 to 100, 20 to 50, 25 to 100, 25 to 50, 30 to 100 or 30 to 50.
[0019] For example, a sunscreen composition of SPF 20 comprises UV filters in a total amount of preferably between 10 and 40 wt.-%, more preferably between 15 and 25 wt.-%, based on the total weight of the composition.
[0020] For example, a sunscreen composition of SPF 50 comprises UV filters in a total amount of preferably between 15 and 50 wt.-%, more preferably between 20 and 40 wt.-%, based on the total weight of the composition.
[0021] In all embodiments of the present invention, a particularly preferred bacterium of the genus P. acnes is P. acnes ATCC 11827.
[0022] The term UV radiation (synonymous with UV light) as used herein refers to radiation in the UVB-UVA range of 280 nm to 400 nm.
[0023] The term outer surface of the human body as used herein refers to the skin as well as the scalp.Preferably, in all embodiments of the present invention, the outer surface of the human body treated according to the present invention is the face, neck and / or body skin.
[0024] The term 'skin microbiome' as used herein refers to the microbial population that colonizes a defined skin area of an individual, such as, but not limited to, the forehead, forearms, cheeks, or scalp.
[0025] In all embodiments of the present invention, the amount of 2-ethylhexyl salicylate (also known as octyl salicylate) in the sunscreen composition according to the present invention is preferably selected from the range of 0.1 wt.% to 20 wt.%, more preferably from 0.1 wt.% to 10 wt.%, most preferably from 0.1 wt.% to 5 wt.%, based on the total weight of the sunscreen composition.
[0026] In all embodiments of the present invention, the amount of butyl methoxydibenzoylmethane (also known as avobenzone, or 3-(4-tert-butylphenyl)-1-(4-methoxyphenyl)propane-1,3-dione) in the sunscreen composition according to the present invention is preferably selected from the range of 0.1 wt.% to 10 wt.%, more preferably from 0.5 wt.% to 7.5 wt.%, most preferably from 1 wt.% to 5 wt.%, based on the total weight of the sunscreen composition.
[0027] In all embodiments of the present invention, the amount of octocrylene (also known as 2-ethylhexyl 2-cyano-3,3-diphenylprop-2-enoate) in the sunscreen composition according to the present invention is preferably selected from the range of 0.1 wt.% to 10 wt.%, more preferably from 0.5 wt.% to 7.5 wt.%, most preferably from 1 wt.% to 5 wt.%, based on the total weight of the sunscreen composition.
[0028] In a specific embodiment, the sunscreen composition according to the invention comprises octocrylene, ethylhexyl salicylate and butyl methoxydibenzoylmethane, more preferably in an amount of 15% to 20% by weight, based on the total weight of the sunscreen composition.
[0029] In another specific embodiment, the sunscreen composition preferably comprises, even more preferably only comprises, ethylhexyl salicylate and ethylhexyl triazone (EHT), or ethylhexyl triazone, bis-ethylhexyloxyphenol methoxyphenyl triazine (BEMT) and butyl methoxydibenzoylmethane. The amount of EHT is preferably selected from the range of 0.1 wt % to 10 wt %, more preferably from 0.5 wt % to 7.5 wt %, most preferably from 1 wt % to 5 wt %, based on the total weight of the sunscreen composition. The amount of BEMPT is preferably selected from the range of 0.1 wt % to 10 wt %, more preferably from 0.5 wt % to 7.5 wt %, most preferably from 0.5 wt % to 5 wt %, based on the total weight of the sunscreen composition.
[0030] Since the sunscreen compositions according to the invention are intended for topical application, it is known that they comprise a physiologically acceptable medium, ie a medium compatible with keratinous materials such as the skin, mucous membranes and keratinous fibers. In particular, the physiologically acceptable medium is a cosmetically acceptable carrier.
[0031] The term 'cosmetically acceptable carrier' as used herein refers to all carriers and / or excipients and / or diluents conventionally used in topical cosmetic compositions, such as in particular in skin care preparations.
[0032] The exact amount of carrier will depend on the actual level of UV filters and any other optional ingredients that one of ordinary skill in the art would classify as different from a carrier (eg, other active ingredients).
[0033] In an advantageous embodiment, the sunscreen composition according to the invention comprises 50 to 99%, preferably 60 to 98%, more preferably 70 to 98%, such as in particular 80 to 95% of carrier, based on the total weight of the sunscreen composition.
[0034] In a particularly advantageous embodiment, the carrier also consists of at least 40 wt. %, more preferably at least 50 wt. %, most preferably at least 55 wt. % water, such as in particular 55 to 90 wt. % water.
[0035] In particular, the sunscreen composition according to the invention is a cosmetic composition or a pharmaceutical composition, preferably a cosmetic (non-therapeutic) composition.
[0036] In one embodiment, the sunscreen composition according to the invention is applied to mammalian keratinous tissue, such as in particular to human skin or human scalp and hair.
[0037] As used in this application, the term "cosmetic composition" refers to Cosmetic compositions as defined under the heading "Kosmetika" in LexikonChemie, 10th edition, 1997, Georg Thieme Verlag Stuttgart, New York, and as disclosed in A. Domsch, "Cosmetic Compositions", Verlag für chemische Industrie (ed. H. Ziolkowsky), 4th edition, 1992.
[0038] The topical compositions according to the invention are also referred to as sun protection preparations (sun protection products, sunscreens), for example sun protection milks, sun protection lotions, sunscreen creams, sun protection oils, sun blocks or tropical creams or day creams with SPF (sun protection factor). Of particular interest are sun protection creams, sun protection lotions, sun protection milks and sun protection preparations.
[0039] The compositions of the invention (including carriers) may contain conventional adjuvants and additives, such as preservatives / antioxidants, fatty substances / oils, organic solvents, silicones, thickeners, emollients, emulsifiers, antifoaming agents, aesthetic components (e.g. fragrances), surfactants, fillers, anionic, cationic, nonionic or amphoteric polymers or mixtures thereof, propellants, acidulants or alkalizers, dyes, colorants / dyes, abrasives, absorbents, chelating and / or sequestrants, essential oils, skin sensates, astringents, pigments, or any other ingredient typically formulated into such compositions.
[0040] According to the invention, the composition according to the invention may comprise further ingredients, for example for lightening the skin; preventing tanning; treating hyperpigmentation; preventing or reducing acne, wrinkles, fine lines, atrophy and / or inflammation; chelating agents and / or chelates; anti-cellulite and slimming (e.g. phytanic acid), firming, moisturizing and revitalizing, self-tanning, soothing ingredients, as well as agents for improving elasticity and the skin barrier, and / or further UV filter substances and carriers and / or excipients or diluents conventionally used in sunscreen compositions.
[0041] If not stated otherwise, the excipients, additives, diluents etc. mentioned below are suitable for use in the sunscreen compositions according to the invention. The necessary amounts of cosmetic and dermatological auxiliaries and additives can be easily determined by the skilled person based on the desired product.
[0042] The additional ingredients may be added to the oil phase, the water phase or separately as appropriate. The mode of addition can be easily adapted by those skilled in the art.
[0043] Examples of cosmetic excipients, diluents, adjuvants, additives and active ingredients commonly used in the skin care industry suitable for use in the cosmetic compositions of the present invention are described, for example, in the International Cosmetic Ingredient Dictionary & Handbook by Personal Care (http: / / www.personalcarecouncil.org / ), provided by the Personal Care Products Council, which can be accessed through the online INFO BASE (http: / / online.personalcarecouncil.org / jsp / Home.jsp), but are not limited thereto.
[0044] In some cases, the cosmetically active ingredients useful herein may provide more than one benefit or operate via more than one mode of action.
[0045] Of course, the person skilled in the art will take care to choose the above-mentioned optional additional ingredients, adjuvants, diluents and additives and / or their amounts so that the advantageous properties essentially associated with the combination according to the invention are not or are not substantially adversely affected by one or more of the envisaged additions.
[0046] The sunscreen composition according to the present invention may be in the form of a suspension or dispersion in a solvent or a fatty substance, or in the form of an emulsion or microemulsion (in particular an oil-in-water (O / W) or water-in-oil (W / O) type, a silicone-in-water (Si / W) or a water-in-silicone (W / Si) type, a PIT emulsion, a multiple emulsion (for example an oil-in-water-in-oil (O / W / O) or a water-in-oil-in-water (W / O / W) type), a Pickering emulsion, a hydrogel, an alcohol gel, a lipogel, a single-phase or multi-phase solution or a vesicular dispersion or other commonly used forms, which may also be applied with a pen-type device as a mask or spray.
[0047] The sunscreen composition according to the invention is advantageously in the form of an oil-in-water (O / W) emulsion comprising an oil phase dispersed in an aqueous phase in the presence of an O / W emulsifier. The preparation of such O / W emulsions is well known to those skilled in the art and is illustrated in the examples.
[0048] In an advantageous embodiment, the O / W emulsifier is a phosphate emulsifier. Among the preferred phosphate emulsifiers there is C 8-10 Alkyl ethyl phosphate, C 9-15 Alkyl phosphate, ceteareth-2 phosphate, ceteareth-5 phosphate, ceteth-8 phosphate, ceteth-10 phosphate, cetyl phosphate, C 6-10 Alkyl ether-4 phosphate, C 12-15 Alkyl ether-2 phosphate, C 12-15 The phosphate emulsifier according to the present invention is potassium cetyl phosphate, which can be used as K was commercially available from DSM Nutritional Products Ltd Kaiseraugst.
[0049] Other suitable O / W emulsifiers according to the present invention include PEG-30 dipolyhydroxystearate, PEG-4 dilaurate, PEG-8 dioleate, PEG-40 sorbitan monooleate, PEG-7 glyceryl cocoate, PEG-20 almond glycerides, PEG-25 hydrogenated castor oil, glyceryl stearate (and) PEG-100 stearate, PEG-7 palm kernelate, PEG-8 oleate, PEG-8 laurate, PEG-60 almond glycerides, PEG-20 methyl glucose sesquistearate, PEG-40 stearate, PEG-100 stearate, PEG-80 Sorbitan laurate, steareth-2, steareth-12, oleth-2, ceteth-2, laureth-4, oleth-10, oleth-10 / PEG-10 oleyl ether, ceteth-10, isosteareth-20, ceteareth-20, oleth-20, steareth-20, steareth-21, ceteth-20, isoceteth-20, laureth-23, steareth-100, glyceryl stearate citrate, glyceryl stearate (self-emulsifying), stearic acid, stearic acid salts, polyglyceryl-3-methylglucose distearate. Other suitable emulsifiers are sorbitan oleate, sorbitan sesquioleate, sorbitan isostearate, sorbitan trioleate, lauryl glucoside, decyl glucoside, sodium stearoyl glutamate, sucrose polystearate and hydrated polyisobutylene. In addition, one or more synthetic polymers can be used as emulsifiers. For example, PVP eicosene copolymer, acrylate / C 10-30 Alkyl acrylate crosspolymer, acrylates / steareth-20 methacrylate copolymer, PEG-22 / dodecyl glycol copolymer, PEG-45 / dodecyl glycol copolymer, and mixtures thereof.
[0050] Another particularly suitable class of O / W emulsifiers are the nonionic self-emulsifying systems derived from olive oil, such as the ones known as (INCI name) cetyl olive oil and sorbitan olivate (chemical composition: sorbitan esters and cetearyl esters of olive oil fatty acids), sold under the trade name OLIVEM 1000.
[0051] Also suitable are commercially available polymeric emulsifiers, such as hydrophobically modified polyacrylic acids, for example acrylates / C10-30 alkyl acrylate crosspolymers, which are available under the trade name TR-1 and TR-2 are commercially available from Noveon.
[0052] Another particularly suitable class of emulsifiers are polyglycerol esters or fatty acid diesters, also known as polyglycerol esters / diesters (i.e. polymers in which one or more fatty acids are bound to polyglycerol by esterification), commercially available, for example, from Evonik as Isolan GPS [INCI name Polyglyceryl-4 diisostearate / polyhydroxystearate / sebacate (i.e. a diester of a mixture of isostearic acid, polyhydroxystearic acid and sebacic acid with polyglyceryl-4)] or from Cognis as Dehymuls PGPH (INCI Polyglyceryl-2 dipolyhydroxystearate).
[0053] Likewise suitable are polyalkylene glycol ethers, for example Brij 72 (polyoxyethylene (2) stearyl ether) or Brij 721 (polyoxyethylene (21) stearyl ether, available for example from Croda).
[0054] Particularly advantageous O / W emulsifiers according to the invention are one or more of the following: polyglyceryl-3 methylglucose distearate, lauryl glucoside (and) polyglyceryl-2 dipolyhydroxystearate, glyceryl stearate citrate, sodium cetearyl sulfate, cetearyl glucoside; polyglyceryl-6 stearate (and) polyglyceryl-6 behenate, olive oil cetyl alcohol esters (and) sorbitan olive oil esters, rosemaryl alcohol esters; Cetearyl Alcohol (and) Behenyl Alcohol (and) Arachidyl Glucoside, Cetearyl Alcohol (and) Coco-Glucoside, Coco-Glucoside (and) Coconut Alcohol, PEG-100 Stearate (and) Glyceryl Stearate, Sodium Stearoyl Glutamate, Steareth-20, Steareth-21, Steareth-25, Steareth-2, Ceteareth-25 and Ceteareth-6 (all listed by their INCI names).
[0055] The most preferred O / W emulsifier according to the present invention is one or more of Ceteareth-6 (optionally blended with stearyl alcohol) and Ceteareth-25.
[0056] The at least one O / W or Si / W type emulsifier is preferably used in an amount of 0.5 to 10 wt.-%, such as specifically in the range of 0.5 to 5 wt.-%, such as most specifically in the range of 0.5 to 4 wt.-%, based on the total weight of the composition.
[0057] Suitable W / O emulsifiers or W / Si emulsifiers according to the invention are: polyglyceryl-2-dipolyhydroxystearate, PEG-30 dipolyhydroxystearate, cetyl dimethicone copolyol, polyglyceryl-3 diisostearate polyglyceryl esters of oleic acid / isostearate, polyglyceryl-6 hexaricinolate, polyglyceryl-4-oleate, polyglyceryl-4-oleate / PEG-8 propylene glycol cocoate, magnesium stearate, sodium stearate, potassium laurate, potassium ricinoleate, sodium cocoate, sodium tallowate, potassium castorate, sodium oleate, and mixtures thereof. Other suitable W / Si emulsifiers are lauryl polyglyceryl-3, polydimethylsiloxyethyl dimethicone and / or PEG-9 polydimethylsiloxyethyl dimethicone and / or cetyl PEG / PPG-10 / 1 dimethicone and / or PEG-12 dimethicone crosspolymer and / or PEG / PPG-18 / 18 dimethicone. A particularly suitable W / O emulsifier to be used in the composition according to the invention is PEG-30 dipolyhydroxystearate. The at least one W / O emulsifier is preferably used in an amount of about 0.001% to 10% by weight, more preferably 0.2% to 7% by weight, relative to the total weight of the composition.
[0058] In addition, the sunscreen composition according to the invention advantageously contains at least one co-surfactant, for example selected from the group consisting of mono- and di-glycerides and / or fatty alcohols. The co-surfactant is usually used in an amount selected from the range of 0.1% to 10% by weight, such as in particular the range of 0.5% to 7% by weight, such as most particularly the range of 1% to 5% by weight, based on the total weight of the composition. Particularly suitable co-surfactants are selected from the following list: alkyl alcohols, such as cetyl alcohol (Lorol C16, Lanette 16), cetearyl alcohol (Lanette O), stearyl alcohol (Lanette 18), behenyl alcohol (Lanette 22), glyceryl stearate, glyceryl myristate (Estol 3650), hydrogenated coconut oil glyceride (Lipocire Na 10) and mixtures thereof.
[0059] In a particularly advantageous embodiment according to the invention, the emulsifier is selected from the group consisting of Ceteareth-6 and / or Ceteareth-25, and the co-surfactant is selected from the group consisting of Behenyl Alcohol, Cetyl Alcohol, Cetearyl Alcohol and / or Stearyl Alcohol.
[0060] The composition in the form of an O / W emulsion according to the invention can be provided, for example, in all formulations of O / W emulsions, for example in the form of serums, emulsions or creams, and they are prepared according to the usual methods. The composition that is the subject of the invention is intended for topical application and can in particular constitute a dermatological or cosmetic composition, which is intended, for example, for protecting human skin from the adverse effects of ultraviolet radiation (anti-wrinkle, anti-aging, moisturizing, sun protection, etc.).
[0061] According to one advantageous embodiment of the invention, the composition constitutes a cosmetic composition and is intended to be applied topically to the skin.
[0062] In an advantageous aspect of the invention, the sunscreen composition according to the invention does not comprise (ie is free of) 3-(4-methylbenzylidene)-camphor and 2-hydroxy-4-methoxybenzophenone (INCI: oxybenzone).
[0063] In another advantageous aspect of the present invention, the sunscreen composition according to the present invention further comprises one or more of dibutyl adipate, dicaprylyl carbonate, stearyl alcohol, C12-C15 alkyl benzoate, caprylyl carbonate, capric / caprylic triglyceride and mixtures thereof, preferably dibutyl adipate, stearyl adipate and / or dicaprylyl carbonate.
[0064] In another advantageous aspect of the invention, the sunscreen composition according to the invention further comprises ethanol, more preferably in an amount of 0.5 to 10 wt.-%, more preferably 3 to 8 wt.-% ethanol, based on the total weight of the sunscreen composition.
[0065] In still another advantageous aspect of the present invention, the sunscreen composition of the present invention further comprises a preservative and / or a preservative synergist, preferably selected from the group consisting of phenoxyethanol, ethylhexylglycerin, hexylglycerin, glyceryl caprylate, caprylyl glycol, 1,2-hexanediol, propylene glycol, propylene glycol, p-hydroxyacetophenone and mixtures thereof, most preferably selected from the group consisting of phenoxyethanol and ethylhexylglycerin and mixtures thereof. When present, the preservative or preservative synergist is preferably used in an amount of 0.01% to 2% by weight, more preferably in an amount of 0.05% to 1.5% by weight, most preferably in an amount of 0.1% to 1.0% by weight, for example 0.1% to 0.5% by weight, based on the total weight of the composition.
[0066] In another advantageous aspect, the sunscreen composition according to the invention does not contain any parabens, benzethonium chloride, piroctone olamine, lauroyl arginine, methylisothiazolinone, chloromethylisothiazolinone, bronopol, benzalkonium chloride, formaldehyde-releasing compounds, salicylic acid, triclosan, DMDM hydantoin, chlorphenesin and IPBC (iodopropynyl butylcarbamate).
[0067] In still further advantageous aspects, the sunscreen composition of the present invention further comprises one or more of glycerin or polyhydroxystearic acid and mixtures thereof.
[0068] In yet still further advantageous aspects, the sunscreen composition of the present invention further comprises a thickener, preferably a gum (such as xanthan gum or Caesalpina spinosa gum), or a polyacrylate (such as polyacrylate crosspolymer-6) and mixtures thereof.
[0069] The pH of the sunscreen composition according to the present invention is generally in the range of 3 to 10, preferably in the range of pH 4 to 8, and most preferably in the range of pH 4 to 7. The pH can be easily adjusted as required with a suitable acid (e.g. citric acid) or base (e.g. NaOH) according to standard methods in the art.
[0070] The sunscreen composition according to the present invention may also contain one or more emollients that soothe and soften the skin. For example, the emollient may be dicaprylyl carbonate or dibutyl adipate. Other emollients are silicones (dimethicone, cyclomethicone), vegetable oils (grape seed oil, sesame seed oil, jojoba oil, etc.), butters (cocoa butter, shea butter), alcohols (stearyl alcohol, cetyl alcohol), and vaseline derivatives (petroleum jelly, mineral oil).
[0071] In still another aspect, the sunscreen composition of the present invention may include potassium cetyl phosphate as an emulsifier, and / or one or more of dibutyl adipate, dicaprylyl carbonate, and stearyl alcohol.
[0072] In yet another aspect, the sunscreen composition of the present invention may comprise an acrylate copolymer, such as acrylate / C 10-30 Alkyl acrylate crosspolymer, even more preferably, an acrylate copolymer in an amount of 0.05 to 1 wt%, more preferably 0.1 to 0.5 wt%, based on the total weight of the sunscreen composition.
[0073] In another aspect, the sunscreen composition of the present invention may comprise one or more fragrances selected from limonene, citral, linalool, α-isomethyl ionone, geraniol, citronellol, 2-isobutyl-4-hydroxy-4-methyltetrahydropyran, 2-tert-amylcyclohexyl acetate, 3-methyl-5-phenyl-1-pentanol, 7-acetyl-1,1,3,4,4,6-hexamethyltetralin, diester of adipate, cinnamaldehyde, amyl salicylate, α-amyl cinnamaldehyde, α-methyl ionone, butylphenyl methylpropional, cinnamaldehyde, amyl cinnamyl alcohol, anise alcohol, benzoin, Benzyl alcohol, benzyl benzoate, benzyl cinnamate, benzyl salicylate, bergamot essential oil, bitter orange oil, butylphenyl methylpropional, cardamom essential oil, cedrol, cinnamaldehyde, cinnamyl alcohol, methyl citronellyl crotonate, citrus oil, coumarin, diethyl succinate, ethyl linalool, eugenol, tree moss extract, oak moss extract, farnesol, guaiac wood oil, hexyl cinnamaldehyde, hexyl salicylate, hydroxycitronellal, lavender oil, lemon oil, linalyl acetate, tangerine peel oil, menthol PCA ester, methyl heptenone, nutmeg oil, rosemary oil, sweet orange oil, terpineol, tonka bean oil, triethyl citrate, vanillin.
[0074] In another aspect, the sunscreen compositions of the present invention may contain at least one salt of 2-phenylbenzimidazole-5-sulfonic acid.
[0075] In another aspect, the composition may have an SPF of at least 20, preferably at least 30.
[0076] The sunscreen compositions according to the invention are treated with surprisingly low total amounts of UV filters.
[0077] According to the invention, it is advantageous if the sunscreen composition is in the form of an emulsion or dispersion, preferably in the form of an emulsion, more preferably in the form of an O / W emulsion.
[0078] In the case where the sunscreen composition of the present invention is in the form of an O / W emulsion, the preparation advantageously comprises one or more O / W emulsifiers selected from the group consisting of glyceryl stearate citrate, glyceryl stearate (self-emulsifying), stearic acid, stearates, polyglyceryl-3-methylglucose distearate, sodium cetearyl sulfate, potassium cetyl phosphate, polyglyceryl-10 stearate and sodium stearyl glutamate.
[0079] Advantageously, according to the invention, these O / W emulsifiers of the invention may be present in the preparation in a concentration ranging from 0.001% to 10% by weight, preferably from 0.1% to 7% by weight, based on the total weight of the preparation.
[0080] According to the invention, it is preferred if the preparation comprises potassium cetyl phosphate as emulsifier.
[0081] According to the invention, it is further advantageous if the preparation comprises cetyl alcohol, stearyl alcohol and / or glyceryl stearate.
[0082] According to the invention, it is advantageous if the preparations according to the invention are free of polyethylene glycols, polyethylene glycol ethers and polyethylene glycol esters (so-called PEG derivatives).
[0083] The preparations according to the invention may advantageously comprise a humectant. A humectant is a compound or a mixture of compounds which imparts to the cosmetic preparation the quality of reducing water loss from the stratum corneum (also known as transepidermal water loss (TEWL)) and / or positively influencing hydration of the stratum corneum after application or distribution on the skin surface.
[0084] Non-limiting examples of advantageous humectants for use in the present invention include glycerol, lactic acid and / or lactates, in particular sodium lactate, butylene glycol, propylene glycol, biosaccharide gum-1, soya bean, ethylhexylglycerol, pyrrolidone carboxylic acid and urea. A further advantage is in particular the use of polymeric humectants from the group of polysaccharides that are water-soluble and / or swellable in water and / or gellable with the aid of water. Particularly advantageous are, for example, hyaluronic acid, chitosan and / or fucose-rich polysaccharides, which are registered in Chemical Abstracts under registration number 178463-23-5 and can be found, for example, under the name 1000 is available from SOLABIAS, A. Moisturizers can also be used advantageously as active anti-wrinkle ingredients to protect against the type of skin changes that occur, for example, with skin aging.
[0085] The cosmetic preparations according to the invention may advantageously (although not obligatory) further comprise fillers which have the effect, for example, of further improving the organoleptic and cosmetic properties of the preparations and of evoking or enhancing, for example, a velvety or silky skin feel. Advantageous fillers in the sense of the present invention are starch and starch derivatives (for example tapioca starch, distarch phosphate, aluminum starch octenylsuccinate or sodium starch octenylsuccinate, etc.), pigments which have neither a substantial UV filter effect nor a coloring effect (for example boron nitride, etc.) and / or (CAS No. 7631-86-9) and / or talc and / or polyethylene, nylon and silica dimethyl silylate.
[0086] Advantageous embodiments of the preparation according to the invention also include those in which the preparation comprises one or more oils selected from the group consisting of butylene glycol dicaprylate / dicaprate, phenethyl benzoate, C12-15 alkyl benzoate, dibutyl adipate; diisopropyl sebacate, dicaprylyl carbonate, di-C12-13 alkyl tartrate, butyloctyl salicylate, diethylhexyl syringylidenemalonate, hydrogenated castor oil dimerates, triheptanoin, C12-13 alkyl lactate, C16-17 alkyl benzoate, propylheptyl caprylate, caprylic / capric triglyceride, diethylhexyl 2,6-naphthalene dicarboxylate, octyldodecanol, ethylhexyl cocoate.
[0087] According to the invention, it is preferred if the preparation comprises dibutyl adipate, dicaprylyl carbonate and / or C12-C15-alkyl benzoate.
[0088] The aqueous phase of the preparation according to the invention can advantageously contain customary cosmetic adjuvants, for example alcohols, in particular low-carbon alcohols, preferably ethanol and / or isopropanol, or low-carbon polyols, and their ethers, preferably propylene glycol, glycerol; electrolytes; self-tanning agents; and in particular one or more thickeners, which can advantageously be selected from the following group: silicon dioxide, aluminum silicate, polysaccharides and / or their derivatives, for example hyaluronic acid, xanthan gum, hydroxypropyl methylcellulose, particularly advantageously from the following group: polyacrylates, preferably from the group known as carbomers, examples being carbomers of types 980, 981, 1382, 2984 and 5984, in each case used alone or in combination. Other thickeners that are advantageous according to the invention are those with the INCI name Acrylates / C10-30 Alkyl Acrylate Crosspolymer (e.g. Pemulen TR 1, Pemulen TR 2, Carbomer 1328 from NOVEON) and also Aristoflex AVC (INCI: Ammonium Acryloyldimethyltaurate / VP Copolymer) and Simugel NS (INCI: Hydroxyethyl Acrylate / Sodium Acryloyldimethyltaurate Copolymer and Squalane and Polysorbate 60).
[0089] According to the invention, it is preferred here if the preparation comprises xanthan gum, crosslinked acrylates / C10-C30 alkyl acrylate polymers, hydroxyethyl acrylate / sodium acryloyldimethyl taurate copolymers and squalane and polysorbate 60 and / or vinylpyrrolidone / hexadecene copolymers.
[0090] According to the invention, an amount of glycerol of at least 2.5% by weight, based on the total weight of the preparation, is particularly advantageous.
[0091] According to the invention, it is advantageous if the preparation comprises one or more alkanediols selected from the group consisting of 1,2-pentanediol, 1,2-hexanediol, 1,2-octanediol, 1,2-decanediol, 2-methyl-1,3-propanediol.
[0092] According to the invention, it is advantageous if the preparation according to the invention comprises ethanol, phenoxyethanol and / or ethylhexylglycerol.
[0093] Advantageously, according to the invention, the preparation according to the invention comprises a film former. Film formers in the sense of the invention are substances in various forms and characterized by the following property: when the film former is dissolved in water or another suitable solvent, when the solution is subsequently applied to the skin, the film former forms a film after evaporation of the solvent, which film essentially serves to fix the filter on the skin and thus increase the water resistance of the product.
[0094] It is particularly advantageous to select the film former from the group of polymers based on polyvinylpyrrolidone (PVP).
[0095] Particularly preferred are copolymers of vinyl pyrrolidone such as, for example, PVP hexadecene copolymer and PVP eicosene copolymer, which are available from GAF Chemicals Corporation under the trade names Antaron V216 and Antaron V220.
[0096] Also advantageous are other polymeric film formers, such as sodium polystyrene sulfonate, which is available from National Starchand Chemical Corp. under the trade name Flexan 130; and / or polyisobutylene, which is available from Rewo under the trade name Rewopal PIB1000. Examples of other suitable polymers are polyacrylamide (Seppigel 305), polyvinyl alcohol, PVP, PVP / VA copolymer, polyethylene glycol, acrylate / octylacrylamide copolymer (Dermacryl 79). Also advantageous is the use of hydrogenated castor oil dimer dioleate (CAS 646054-62-8, INCI hydrogenated castor oil dimer dioleate), which is available from Kokyu Alcohol Kogyo under the name Risocast DA-H; or PPG-3 benzyl ether myristate (CAS 403517-45-3), which is available from Croda Chemicals under the trade name Crodamol STS.
[0097] According to the invention is the use of the preparations according to the invention for protection against skin ageing, in particular against UV-induced skin ageing, and as sunscreen compositions.
[0098] The following examples are provided to further illustrate the compositions and effects of the present invention. These examples are illustrative only and are not intended to limit the scope of the present invention in any way. Example
[0099] In vitro UV model
[0100] The microbial strains used in this study are listed below and their cultures were reconstituted according to the instructions of the supplier's reference strain collection ATCC (American Type Culture Collection):
[0101] Propionibacterium acnes ATCC 11827
[0102] Staphylococcus epidermidis ATCC 12228
[0103] The recommended culture medium (140 μ L) is filled in 96 well plates, and the calibrated inoculum (20 μ L) of every kind of bacterial strain is added to reach a final concentration of 1.106 colony forming units / milliliter (cfu / mL). After contamination, samples (40 μ L; 20% v / v) are added in triplicate, and fully mixed to ensure uniform distribution. Then, according to the UV dosage shown in the following table 1, plates are subjected to UV stress by UV irradiator system (BioSun, Vilber Lourmat, France). The selected specific UV dosage is for making the survival rate of the microbial colony between 10% and 49%.
[0104] Table 1. Selection of UV irradiation conditions for each microbial strain. The energy ratio between UVA and UVB is 1:19. ±*: the survival rate of the microbial population is between 21% and 49%; ±: the survival rate of the microbial population is between 50% and 79%.
[0105] strains SED(unit) <![CDATA[UVA+UVB(mJ / cm 2 )]]> Survival rate after 4 hours (%) Propionibacterium acnes 3 30 ± Staphylococcus epidermidis 15 150 ±*
[0106] The enumeration of the P. acnes microbial population was performed by inoculating aliquots onto agar plates and was performed in triplicate. The enumeration of the P. acnes colonies grown was used to determine the reduction rate of the microbial population. The control performed during this experiment was a culture medium containing bacteria incubated without UV stress. The microbial population counts are expressed in cfu / mL and are the average of experiments performed in triplicate.
[0107] For sampling and microbial population enumeration, aliquots of contaminated samples of Staphylococcus epidermidis were serially diluted (4 ten-fold dilutions followed by 8 two-fold dilutions in triplicate) in a medium on a 96-well plate containing triphenyltetrazol. The plates were then incubated at 37°C ± 2,5°C during 48h, taking into account the respiratory type of each strain. After 48h under optimal growth conditions, the final dilution exhibited a pink color (triphenyltetrazol), or turbidity indicating the contamination rate and allowing determination of the reduction rate of the microbial population (most probable number (MPN) method).
[0108] The use levels of single UV filters and combinations in the test formulations were calculated to obtain predicted in vitro SPF values of 5.75 + / - 0.15 and 23.45 + / - 0.65, respectively (Table 2). The UV filters were mixed in two oils, Tegosoft XC (55%) and Miglyol 829 Eco (ad 100%), and the emulsifier Tween 80 (5%).
[0109] The effect of selected UV irradiation conditions on the survival of the microbial populations Propionibacterium acnes and Staphylococcus epidermidis in the presence of 20% v / v of the test samples 1-10 was compared with the corresponding strains (control) in the absence of samples 1-10 and without exposure to UV irradiation. The results after 4 hours of incubation were compared with the bacterial population incubated without UV stress (determination of bacterial population survival) and expressed as a percentage of survival (%). The relative protection percentage (%) was calculated based on the difference between the survival percentages of the sample and the vehicle control (with UV irradiation) divided by the survival percentage of the vehicle control. Therefore, the survival rate of each microbial population and the relative protection achieved by the UV filter were calculated and summarized in Table 2.
[0110] Table 2. Test formulations of UV filters and ingredients in % by weight (* mixed with 55% Tegosoft XC, ad100% Miglyol 829 Eco, 5% Tween 80). The survival results for each microbial population are calculated in % compared to the untreated and non-irradiated control. In brackets: the relative protection achieved by the UV filters is given in % relative to the vehicle control.
[0111]
[0112]
[0113] abbreviation INCI name OC Octocrylene BMDBM Butyl Methoxydibenzoylmethane ZnO Tecs Zinc oxide, triethoxycaprylylsilane EHT Ethylhexyl triazone BEMT Bis-ethylhexyloxyphenol methoxyphenyl triazine EHS Ethylhexyl salicylate <![CDATA[TiO2 / SiO2 / D]]> Titanium dioxide, silicon dioxide, polydimethylsiloxane
[0114] We tested the phylotype IA strain of Propionibacterium acnes ATCC 11827, which is a conditional pathogen that may be associated with acne skin. Selected UV filters, such as BMDBM, EHS and octocrylene, as well as the combination of octocrylene, EHS and EHT, and EHT, BEMT and BDMBM, reduced the population of Propionibacterium acnes in the skin microbiota after UV irradiation, while maintaining or even proliferating the commensal bacteria Staphylococcus epidermidis to exacerbate the progression of acne skin.
Claims
1. A method of reducing Propionibacterium acnes in the skin microbiome of a person in need thereof, the method comprising the step of applying to an external surface having a skin microbiome comprising Propionibacterium acnes and optionally Staphylococcus epidermidis to UV radiation an effective amount of a sunscreen composition comprising one or more UV filters selected from the group consisting of octocrylene, ethylhexyl salicylate and butyl methoxydibenzoylmethane.
2. The method according to claim 1, wherein the Staphylococcus epidermidis is simultaneously protected from the harmful effects of UV radiation.
3. The method according to claim 1 and / or 2, wherein the reduction of P. acnes is characterized by a decrease in survival rate of at least -10%, preferably at least -30%, most preferably at least -60% compared to a control after exposure to UV radiation.
4. The method according to any one or more of the preceding claims, wherein the protection against Staphylococcus epidermidis is characterized in that after exposure to UV radiation the survival rate is increased by at least 20% compared to a control.
5. The method according to any one or more of claims 1 to 4, wherein the amount of the one or more UV filters in the sunscreen composition is selected such that the sunscreen composition exhibits an SPF of at least 20.
6. The method of claim 1, wherein the Propionibacterium acnes is strain Propionibacterium acnes ATCC11827.
7. The method according to any one or more of claims 1 to 6, for treating or preventing disorders of the skin following UV radiation.
8. The method according to any one or more of claims 1 to 7, wherein the amount of butyl methoxydibenzoylmethane is selected from the range of 0.1 wt.-% to 10 wt.-%, preferably from 0.5 wt.-% to 7.5 wt.-%, most preferably from 1 wt.-% to 5 wt.-%, based on the total weight of the sunscreen composition.
9. The method according to any one or more of claims 1 to 8, wherein the amount of octocrylene is selected from the range of 0.1 wt.-% to 10 wt.-%, more preferably from 0.5 wt.-% to 7.5 wt.-%, most preferably from 1 wt.-% to 5 wt.-%, based on the total weight of the sunscreen composition.
10. The method according to any one or more of claims 1 to 9, wherein the amount of ethylhexyl salicylate in the sunscreen composition is selected from the range of 0.1 wt.-% to 20 wt.-%, preferably from 0.1 wt.-% to 10 wt.-%, most preferably from 0.1 wt.-% to 5 wt.-%, based on the total weight of the sunscreen composition.
11. Use of octocrylene, ethylhexyl salicylate and / or butyl methoxydibenzoylmethane for preventing or treating acne.
12. A sunscreen composition comprising one or more UV filters selected from the group consisting of octocrylene, ethylhexyl salicylate and butyl methoxydibenzoylmethane, for use in preventing or treating acne.
13. The sunscreen composition for preventing or treating acne according to claim 12, wherein the amount of butyl methoxydibenzoylmethane is selected from the range of 0.1 wt % to 10 wt %, preferably from 0.5 wt % to 7.5 wt %, most preferably from 1 wt % to 5 wt %, based on the total weight of the sunscreen composition.
14. The sunscreen composition for preventing or treating acne according to claim 12 and / or 13, wherein the amount of octocrylene is selected from the range of 0.1 wt % to 10 wt %, more preferably from 0.5 wt % to 7.5 wt %, most preferably from 1 wt % to 5 wt %, based on the total weight of the sunscreen composition.
15. A sunscreen composition for preventing or treating acne according to any one or more of claims 12 to 14, wherein the amount of ethylhexyl salicylate in the sunscreen composition is selected from the range of 0.1 wt % to 20 wt %, preferably from 0.1 wt % to 10 wt %, most preferably from 0.1 wt % to 5 wt %, based on the total weight of the sunscreen composition.