Patent Grant
10065052
This application is a US National Stage of International Application No. PCT/GB2010/051170, filed 19 Jul. 2010, which claims the benefit of GB 0912481.9, filed 17 Jul. 2009, both herein fully incorporated by reference.
This invention relates to skincare compositions, in particular compositions effective in the treatment of acne vulgaris, and to methods of treatment of the skin that involve the application of such compositions.
Acne vulgaris (acne) is a chronic inflammatory condition of the pilosebaceous units of the skin, which is particularly prevalent in adolescents. The condition generally causes the formation, on the skin, of comedones, red papules, pustules and sometimes cysts. This is unsightly and furthermore, if untreated, acne can lead to scarring of the skin. The major causes of acne are thought to be an increase in sebum production, an increased presence of propionibacterium acne (P. acne), blockage of the pilosebaceus duct and the production of inflammation.
Salicylic acid is known to be effective in the treatment of acne. It is a topical keratolytic agent that works by dissolving the intercellular cement that holds epithelial cells together. Salicylic acid is used in a variety of over-the-counter acne remedies.
In order to improve the efficacy of topical acne treatments, it is desired to formulate salicylic acid with one or more control agents to regulate the inflammatory effects sometimes observed, such as local skin peeling and discomfort such as burning and skin reddening.
Surprisingly, it has now been found that skincare compositions comprising salicylic acid and at least two or more chosen actives have improved therapeutic efficacy in the treatment of acne. Said skincare compositions have both the ability to treat acne and reduce the appearance of redness on the skin.
Thus, according to a first aspect of the invention there is provided a skincare composition suitable for topical application to the skin, the composition comprising salicylic acid or a salt thereof, combined with at least 2 actives selected from the group consisting of:
It has been found that this treatment provides advantages over existing acne treatments, particularly in tolerance of the acne treatment by the skin. It may have an effect in reducing the severity of the acne and hence any associated marks or scarring that can occur; furthermore, cutaneous irritation may be reduced. Other measures indicating advantages are the reduction in inflammation in the affected skin and/or a soothing effect. A synergistic association between the chosen combination of ingredients may provide that a composition may have lesser amounts of each individual ingredient
Salicylic acid is preferably incorporated into the composition according to the invention as the free acid. However, the pH of the composition may, and generally will, be such that the salicylic acid exists in the composition in dissociated form. As the composition may well contain cationic counterions, the salicylic acid may then be thought of as being present in salt form. Alternatively, the salicylic acid may be incorporated into the composition already in salt form, eg as a salt with a Group I metal, such as sodium salicylate. As used herein, unless the context requires otherwise, any and all references to salicylic acid should be taken to encompass references to the acid and to dissociated forms and salts thereof.
The concentration of salicylic acid in the composition according to the invention is preferably at least 0.01 percent by weight, more preferably at least 0.1 percent, most preferably at least 0.5 percent and especially at least 1 percent by weight. The concentration of salicylic acid is preferably less than 10 percent, more preferably less than 5 percent, most preferably less than 4 percent and especially less than 3 percent by weight. The concentration of salicylic acid may therefore fall in the range 0.01 percent to 10 percent by weight, more preferably 0.1 percent to 5 percent, and most preferably 0.5 percent to 4 percent and especially 1 to 3 percent by weight. A particularly preferred concentration of salicylic acid is 2 percent by weight.
The concentration of lactic acid or salt thereof when present in the composition is at least 0.01 percent by weight, more preferably at least 0.1 percent by weight and most preferably at least 1 percent by weight; and is less than 10 percent by weight, more preferably less than 5 percent by weight, and most preferably less than 3 percent by weight.
The concentration of glycyrrhizinic acid or a salt or a derivative thereof when present in the composition is at least 0.01 percent by weight and is less than 2 percent by weight, more preferably less than 1 percent by weight, and most preferably less than 0.5 percent by weight.
The concentration of bisabolol when present in the composition is at least 0.001 percent by weight, more preferably at least 0.01 percent by weight and is less than 1 percent by weight, more preferably less than 0.5 percent by weight,
The concentration of cetylhydroxyproline palmitamide when present in the composition is at least 0.001 percent by weight, more preferably at least 0.01 percent by weight and is less than 1 percent by weight, more preferably less than 0.5 percent by weight.
The concentration of allantoin when present in the composition is at least 0.01 percent by weight, more preferably at least 0.1 percent by weight and most preferably at least 0.2 percent by weight, and is less than 5 percent by weight, more preferably less than 2 percent by weight, and most preferably less than 1 percent by weight.
The concentration of niacinamide when present in the composition is at least 0.01 percent by weight, more preferably at least 0.1 percent by weight and most preferably at least 0.5 percent by weight, and is less than 10 percent by weight, more preferably less than 5 percent by weight.
The concentration of epilobium angustifolium extract when present in the composition is at least 0.01 percent by weight, and is less than 5 percent by weight, more preferably less than 1 percent by weight, and most preferably less than 0.5 percent by weight.
In a particularly preferred embodiment of the present invention, there is provided a skincare composition comprising 0.1 to 5 wt % salicylic acid, or a salt thereof, in combination with at least 2 actives selected from the group consisting of:
In a further particularly preferred embodiment of the present invention, there is provided a skincare composition comprising 1 to 3 wt % salicylic acid or a salt thereof; in combination with at least 2 actives selected from the group consisting of:
The composition is preferably prepared with a pH in the range 2.5 to 8.0, more preferably 3.0 to 7.0, and particularly a pH in the range 3.5 to 6.0, e.g. about pH 4.5 or pH 5.5.
A composition according to the invention may comprise one or more further topically active ingredients useful in skincare. Such active ingredients may include one or more of the following:
antimicrobial or antibacterial compounds, for example selected from the following: triclosan, neomycin, clindamycin, polymyxin, bacitracin, benzoyl peroxide, hydrogen peroxide, tetracylines such as doxycycline or minocycline, sulfa drugs such as sulfacetamide, penicillins, cephalosporins such as cephaiexin, and quinolones such as lomefloxacin, olfoxacin or trovafloxacin;
antiviral compounds, for example selected from acyclovir, tamvir, and penciclovir;
antifungal compounds, for example selected from the following: framesol, clotrimazole, ketoconazole, econazole, fluconazole, calcium or zinc undecylenate, undecylenic acid, butenafine hydrochloride, ciclopirox olaimine, miconazole nitrate, nystatin, sulconazole, and terbinafine hydrochloride; anti-inflammatory compounds, for example selected from the following: steroidal agents selected from hydrocortisone, fluocinolone acetonide, halcinonide, halobetasol propionate, clobetasol propionate, betamethasone dipropionate, betamethasone valerate, and triamcinolone acetonide, and non-steroidal anti-inflammatory agents selected from aspirin, ibuprofen, ketoprofen, naproxen, aloe vera gel, aloe vera, licorice extract, pilewort or zinc;
anthelmintic compounds, for example metronidazole.
The composition according to the invention may be formulated in numerous forms. However, the composition may often take the form of an aqueous or oily solution or surfactant wash or dispersion or emulsion or a gel. An emulsion may be an oil-in-water emulsion or a water-in-oil emulsion or microemulsion.
The oil phase of emulsions may comprise, but are not exclusive to: hydrocarbon oils such as paraffin or mineral oils; b) waxes such as beeswax or paraffin wax; c) natural oils such as sunflower oil, apricot kernel oil, shea butter or jojoba oil; d) silicone oils such as dimethicone, cyclomethicone or cetyldimethicone; e) fatty acid esters such as isopropyl palmitate, isopropyl myristate, dioctylmaleate, glyceryl oleate and cetostearyl isononanoate; f) fatty alcohols such as cetyl alcohol or stearyl alcohol and mixtures thereof (eg cetearyl alcohol); g) polypropylene glycol or polyethylene glycol ethers, eg PPG-14 butyl ether; or h) mixtures thereof, for example, the blend of waxes available commercially under the trade name Cutina (Henkel).
Emulsifiers used may be any emulsifiers known in the art for use in water-in-oil or oil-in-water emulsions or microemulsions. Known cosmetically acceptable emulsifiers may include: a) sesquioleates such as sorbitan sesquioleate, available commercially for example under the trade name Arlacel 83 (ICI), or polyglyceryl-2-sesquioleate; b) ethoxylated esters of derivatives of natural oils such as the polyethoxylated ester of hydrogenated castor oil available commercially for example under the trade name Arlacel 989 (ICI); c) silicone emulsifiers such as silicone polyols available commercially for example under the trade name ABIL WS08 (Th. Goldschmidt AG); d) anionic emulsifiers such as fatty acid soaps e.g. potassium stearate and fatty acid sulphates e.g. sodium cetostearyl sulphate available commercially under the trade name Dehydag (Henkel); e) ethoxylated fatty alcohols, for example the emulsifiers available commercially under the trade name Brij (ICI); f) sorbitan esters, for example the emulsifiers available commercially under the trade name Span (ICI); g) ethoxylated sorbitan esters, for example the emulsifiers available commercially under the trade name Tween (ICI); h) ethoxylated fatty acid esters such as ethoxylated stearates, glyceryl monostearates for example the emulsifiers available commercially under the trade name Myrj (ICI); i) ethoxylated mono-, di-, and tri-glycerides, for example the emulsifiers available commercially under the trade name Labrafil (Alfa Chem.); j) non-ionic self-emulsifying waxes, for example the wax available commercially under the trade name Polawax (Croda); k) ethoxylated fatty acids, for example, the emulsifiers available commercially under the trade name Tefose (Alfa Chem.)
l) methylglucose esters such as polyglycerol-3 methyl glucose distearate available commercially under the name Tegocare 450 (Degussa Goldschmidt); m) as well as polyacrylamide emulsifier systems for examples cream gel emulsifier under trade name Sepigel 305 (Seppic) or n) mixtures thereof.
Gels provided according to the invention may be aqueous or non-aqueous. Aqueous gels are preferred. The gel will contain a gelling agents in order to give sufficient viscosity to the gel. Suitable gelling agents may be hydroxypropyl guar or a copolymer of acryloyl dimethyl tauric acid (or a salt thereof), especially a copolymer of that monomer with another vinylic monomer. The salt may be a salt of a Group I alkali metal, but is more preferably an ammonium salt. Examples of suitable copolymer gelling agents are ammonium acryloyl dimethyl taurate/vinyl pyrrolidone copolymer, ammonium acryloyl dimethyl taurate/Beheneth-25 methacrylate copolymer, ammonium acryloyldimethyltaurate/vinyl formamide copolymer These materials are available from Clariant GmbH in the range of products under the trade name Aristoflex.
A variety of thickening agents may also be used according to the nature of the liquid carrier and the viscosity required. Thickeners that are water-soluble or hydrophilic are preferred, and examples include acrylic acid polymers, eg those available commercially under the trade name Carbopol (B.F. Goodrich), modified celluloses, eg hydroxypropylmethylcellulose or hydroxyethylcellulose available commercially under the trade name Natrosol (Hercules), alkylgalactomanans available under the trade name N-Hance, xanthan gum, cetyl alcohol and sodium chloride.
The amount of gelling and/or thickening agent in the composition will each preferably lie in the range 0.1 to 5 percent w/w, more preferably 0.5 to 5 percent w/w. Typically, the amount of gelling and/or thickening agent will each be less than 3 percent w/w, eg about 1 percent w/w or about 2 percent w/w.
The composition according to the invention preferably has a viscosity of from about 10,000 mPa·s to about 200,000 mPa·s, Viscosity may be measured using a Brookfield RVT viscometer equipped with a T bar C rotating at 5 rpm for 1 minute.
In many instances, it is preferred that the composition should comprise a chelating or sequestering agent, or other agent capable of complexation or other interaction with metal ions present in the composition. Such agents may improve the stability of the composition, and in particular may inhibit or prevent degradation of several ingredients (eg fragrance). Examples of chelating or sequestering agents include ethylenediamine tetraacetic acid and its salts, notably the dipotassium and especially the disodium salt.
In the case of solutions or dispersions, and gels, the composition will generally contain a solvent system or other continuous liquid phase. Such a system is preferably aqueous. However, mixed solvent systems may often be used with advantage. Such a mixed solvent system most preferably comprises water, in admixture with a co-solvent, most preferably a lower (eg C1-6) alcohol, in particular ethanol and t-butyl alcohol.
Preferred aqueous systems comprise water in an amount of at least 25 percent by weight, more preferably at least 35 percent by weight, The upper limit of water will depend on the amounts of other ingredients incorporated in the composition so that the water may form the remainder of the composition up to 100 percent of the composition.
The composition may additionally comprise other components which will be well known to those skilled in the art. These include, for example:
a) Emollients—ingredients that help to maintain the soft, smooth and pliable appearance of skin. Such ingredients may function by their ability to remain on the surface of the skin or in the stratum corneum, and to act as lubricants, reducing or preventing flaking of the skin and improving the skin's appearance. Examples of emollients are isopropyl myristate, triglycerides of fatty acids eg lauric triglyceride or capric/caprylic triglyceride, such as the triglyceride available commercially under the trade name Miglyol 810 (Huls UK), and the polypropylene glycol ether of stearyl alcohol known as PPF-15 Stearyl Ether. Particularly preferred emollients are octyldodecanol and polysiloxane compounds, in particular those known as dimethicones.
b) Humectants or Moisturisers—ingredients intended to increase the water content of the top layers of the skin. Examples of such ingredients are glycerin, sorbitol, 1,3-butylene glycol and propylene glycol.
c) Surfactants—Surfactants may be used in compositions according to the invention as solubilisers, or as cleansing agents or foam boosters. Many different classes of surfactant may be suitable for inclusion in the composition according to the invention, and these will be readily apparent to those skilled in the art. Examples of suitable surfactants include anionic surfactants (eg sodium laureth sulphate, non ionic surfactants (eg cocoglucoside) cationic surfactants and/or amphoteric surfactants (eg cocoamidoproyl betaine). Polyethylene glycol ethers of alcohols such as isocetyl alcohol (eg Isoceteth-20), isostearyl alcohol (eg Isosteareth-20), cetyl alcohol (eg Ceteth-20), oleyl alcohol (eg Oleth-20) and cetearyl alcohol (eg Ceteareth-20).
d) Preservatives—ingredients which prevent or retard microbial growth and thus protect the composition from spoilage. Examples of preservatives include such as propylparaben, bronopol, sodium dehydroacetate, polyhexamethylenebiguanide hydrochloride, isothiazolone and diazolidinylurea.
e) Chelating agents or sequestering agents (sequestrants)—ingredients that have the ability to complex with and inactivate metallic ions in order to prevent their adverse effects on the stability or appearance of the composition, as described above. Examples of chelating agents are ethylenediamine tetraacetic acid and its salts, notably the dipotassium and especially the disodium or tetrasodium salt.
f) Abrasives—ingredients used to assist in the removal of unwanted tissue or foreign materials from the skin during application of the composition. Abrasives commonly comprise fine solid particles. Examples of suitable abrasives are polyethylene beads and aluminium oxide
g) opacifying agents such as clays (eg kaolin and bentonite) as well as titanium dioxide.
h) pH adjusters—Ingredients used to control the pH of the composition. Examples of pH adjusters are inorganic salts such as sodium hydroxide, and organic bases such as triethanolamine and arginine.
i) Conditioning agents, for example distearyldimonium chloride.
j) Perfumes and colourings.
The composition according to the invention may be applied and left on the skin to have the desired therapeutic effect or it may be applied and then rinsed off, for example with water for surfactant based formulations. The composition may be applied with the aid of a fibrous material, for example a pad or a wipe.
According to another aspect of the invention, there is provided an article comprising a fibrous substrate, for example a material in the form of a pad or a wipe, impregnated with a skincare composition comprising salicylic acid or a salt thereof and at least 2 actives selected from the group consisting of lactic acid or a salt thereof; glycyrrhizinic acid or a salt or derivative thereof; bisabolol; cetylhydroxyproline palmitamide; allantoin; niacinamide; and, and epilobium angustifolium extract.
The fibrous material may be used to apply the composition onto the skin.
Suitable fibrous materials include cellulose or cotton fibres or a mixture thereof. The fibrous material may be impregnated with the composition as a wet wipe which is arranged for immediate use to apply the skincare composition of the present invention to the skin of the user. Alternatively, the fibrous material may be impregnated with the skincare composition and dried to form a dry wipe which requires to be wetted, for example with water, before it can be used.
According to a further aspect of the invention, there is provided method for the prophylactic or remedial treatment of acne, which method comprises the topical application to the skin of a patient of a skincare composition comprising salicylic acid or a salt thereof and at least 2 of the list comprising lactic acid or a salt thereof; glycyrrhizinic acid or a salt and their derivatives, bisabolol; cetylhydroxyproline palmitamide, allantoin, niacinamide. and epilobium angustifolium extract.
It will be appreciated that the method according to this aspect of the invention may be a therapeutic method, but will often be a primarily cosmetic method, the objective of which is to reduce or eliminate externally visible, and often unsightly, symptoms of acne vulgaris.
In a yet further aspect of the invention, there is provided the use of salicylic acid and at least 2 actives selected from the group consisting of lactic acid (or salts thereof); glycyrrhizinic acid (or salts or derivatives thereof); bisabolol; cetylhydroxyproline palmitamide; allantoin; niacinamide and epilobium angustifolium in the manufacture of a composition for the prophylactic or remedial treatment of acne by topical application of the composition to the skin.
The invention will now be described in greater detail, by way of illustration only, with reference to the following Examples.
Example 1: Serum
Example 2: Clear gel scrub
Example 3: Pearlised Gel Scrub
Example 4: Wash/mask
Example 5: Wash/mask
Example 6: Hydro alcoholic gel
Example 7: Cream Scrub
Example 8: Foaming Cream Scrub
The composition of each of these examples is shown fully in the following Tables 1-8.
Brassica
Campestris
Epilobium
angustifolium
Brassica
Campestris
Epilobium
angustifolium
Brassica
Campestris
Epilobium
angustifolium
Brassica
Campestris
Epilobium
angustifolium
Brassica
Campestris
Epilobium
angustifolium
Brassica
Campestris
Epilobium
angustifolium
Brassica
Campestris
Epilobium
angustifolium
Brassica
Campestris
Epilobium
angustifolium
Brassica Campestris
Brassica Campestris
The purpose of the in vitro testing was to evaluate the potential anti-inflammatory action of compositions according to the present invention.
In vitro tests were carried out as follows:
Experimental design follows standard procedures, using phorbol-12-myristate 13-acetate (PMA) as irritant. Test samples were applied by pipette as solutions to the Epiderm tissue, and each sample was tested in triplicate against positive and negative controls. Anti-inflammatory activity measured by relative decrease in cytokine release in irritant-treated tissue compared to non-irritant treated tissue.
The separate active components of an example according to the invention were tested, along with some combinations in pairs and one combination lacking the salicylic acid. Where these actives were applied, they were in the same w/w ratio as in the example composition, example 9. The data shown in the table are the cytokine release values in pg/ml, wherein a lower figure shows a lower release rate of cytokines i.e. a lower inflammation.
It will be seen that salicylic acid alone acts inter alia as an anti-inflammatory, but that unexpectedly it also acts with the combination of ingredients in the example according to the invention to reduce significantly the inflammatory behaviour of each of these ingredients. This synergistic behaviour is totally unexpected and permits the formulation of products according to the invention such as the one tested which have a broad range of active ingredients to deal with traumas arising from every stage in the lifecycle of a specific acne event or related skin inflammation.
| Number | Date | Country | Kind |
|---|---|---|---|
| 0912481.9 | Jul 2009 | GB | national |
| Filing Document | Filing Date | Country | Kind | 371c Date |
|---|---|---|---|---|
| PCT/GB2010/051170 | 7/19/2010 | WO | 00 | 3/2/2012 |
| Publishing Document | Publishing Date | Country | Kind |
|---|---|---|---|
| WO2011/007183 | 1/20/2011 | WO | A |
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| Number | Date | Country | |
|---|---|---|---|
| 20120189684 A1 | Jul 2012 | US |
