Patent Publication Number: US-2012039826-A1

Title: Cosmetic composition for skin lightening

Description:
TECHNICAL FIELD 
     The present invention relates to a cosmetic composition for skin lightening. 
     BACKGROUND OF THE INVENTION 
     Consumers, particularly from Asia, prefer a lighter skin colour and therefore skin lightening has been an active area of research in the past. Some consumers believe that skin lightening agents used in the past have undesirable side effects and/or are relatively less efficacious. The skin lightening efficacy is relatively low when the consumer skin is exposed to a source of UV radiation such as sunlight. 
     Further, some skin lightening agents, when included in a cosmetic composition have a negative effect on the spreading characteristics and sensory feel of the composition on the skin 
     One of the objects of the present invention is to overcome or ameliorate at least one of the disadvantages of the prior art, or to provide a useful alternative. 
     Another object of the present invention is to provide a cosmetic composition for skin lightening that is relatively more efficacious. 
     Yet another object of the present invention is to provide a cosmetic composition for skin lightening that has relatively better spreading characteristics and acceptable sensory feel. 
     Present inventors have surprisingly found that certain specific salts of acetic acid viz. the potassium and magnesium salts provide enhanced efficacy in skin lightening as compared to other salts of low molecular weight carboxylic acid when incorporated in a cosmetic composition at a certain range. 
     EP 0 345 082 (1989) discloses a pharmaceutical agent to suppress the formation of an enzyme that prevents the formation of tyrosinase viz. members selected from the group consisting of acetic acid, lactic acid, pyruvic acid and their salts. 
     The disclosures in published documents heretofore do not disclose the specific selection of salts of acetic acids in a certain range for providing skin lightening. 
     SUMMARY OF THE INVENTION 
     According to the present invention there is provided a cosmetic composition for skin lightening comprising: 
     (a) 0.5 to 10% by weight salt of a potassium or magnesium acetate; and 
     (b) a cosmetically acceptable carrier. 
     DETAILED DESCRIPTION OF THE INVENTION 
     The composition of the present invention is preferably for non-therapeutic use, more preferably for a cosmetic use. 
     These and other aspects, features and advantages will become apparent to those of ordinary skill in the art from a reading of the following detailed description and the appended claims. For the avoidance of doubt, any feature of one aspect of the present invention may be utilised in any other aspect of the invention. The word “comprising” is intended to mean “including” but not necessarily “consisting of” or “composed of.” In other words, the listed steps or options need not be exhaustive. It is noted that the examples given in the description below are intended to clarify the invention and are not intended to limit the invention to those examples per se. Similarly, all percentages are weight/weight percentages unless otherwise indicated. Except in the operating and comparative examples, or where otherwise explicitly indicated, all numbers in this description indicating amounts of material or conditions of reaction, physical properties of materials and/or use are to be understood as modified by the word “about”. Numerical ranges expressed in the format “from x to y” are understood to include x and y. When for a specific feature multiple preferred ranges are described in the format “from x to y”, it is understood that all ranges combining the different endpoints are also contemplated. The disclosure of the invention as found herein is to be considered to cover all embodiments as found in the claims as being multiply dependent upon each other irrespective of the fact that claims may be found without multiple dependency or redundancy. 
     Potassium or Magnesium Acetate 
     The cosmetic composition comprises 0.5 to 10% by weight, preferably from 1 to 8% by weight, more preferably from 1 to 5% by weight potassium or magnesium acatete. Of these two salts, magnesium acetate is particularly preferred. The present inventors have determined that the potassium and magnesium acetates are far superior in providing skin lightening as compared to other alkali or alkali metal acetates. Further, they have also found that these two salts are superior to salts of other carboxylic acids of low molecular weight e.g. lactates, tartarates or propionates in providing skin lightening. 
     Polymer 
     The cosmetic composition for skin lightening preferably comprises a polymer selected from a homopolymer or a copolymer of acrylic acid, vinyl alcohol, vinyl pyrollidone, or ethylene oxide. 
     The polymer is preferably from 0.1 to 5% by weight, more preferably from 0.5 to 5% by weight and most preferably from 0.5 to 3% by weight of the cosmetic composition. 
     The polymer may be a crosslinked polymer. Preferred crosslinking agent is polyethylene glycol of divinyl benzene. 
     Some examples of commercially available polymers that can be used include: ACULYN 33™ (Rohm and Haas) -Acrylic acid copolymer emulsion, 
     ROVACE™ HP-2931 (Rohm and Haas)—Vinyl acetate/acrylic copolymer, 
     SUNSPHERES™ (Rohm and Haas)—styrene/acrylic copolymer spheres, 
     Structure Plus™ (National starch)—Acrylates/aminoacrylates/C10-30 alkyl PEG-20 itaconate copolymer, 
     Structure 3001™ (National starch)—Acrylates/Ceteth-20 itaconate copolymer, 
     Structure 2001™ (National starch)—Acrylates/Steareth-20 itaconate copolymer, and 
     Pemulen™ (Lubrizol)—Acrylates/C10-30 alkyl acrylate crosspolymer. 
     The molecular mass of the polymer is preferably greater than 50000, more preferably greater than 90000, and most preferably greater than 100000. The polymer, the acetate salt and an aqueous solution are preferably premixed together to form an adduct prior to adding to the composition. Without wishing to be bound by theory it is believed that the inclusion of the polymer synergistically interacts with the acetate salt in providing the right balance of spreading of the composition on the skin and the biochemical reaction necessary for the skin lightening action while not compromising on the feel and other sensory properties that the consumers expect to get from such a product. 
     Cosmetically Acceptable Carrier 
     Compositions of this invention comprise a cosmetically acceptable carrier. Amount of the carrier can be up to 99.5% by weight of the composition. However, the carrier is more preferably from 70 to 95%, and most preferably from 80 to 90% by weight of the composition. Among the useful carriers are water, saturated emollients, saturated fatty acids, saturated fatty alcohols, humectants, thickeners or combinations thereof. The carrier may be aqueous, anhydrous or an emulsion. 
     Preferably the compositions are aqueous, especially water and oil emulsions of the W/O or O/W or triplex W/O/W variety. Water when present is preferably from 5 to 95%, more preferably from 10 to 80%, most preferably from 20 to 75% by weight of the composition. 
     Fatty acids having from 10 to 30 carbon atoms are also suitable as cosmetically acceptable carriers. Illustrative of this category are pelargonic, lauric, myristic, palmitic, stearic, isostearic, hydroxystearic and behenic acids. A preferred cosmetically accepted carrier is the so-called vanishing cream base. The vanishing cream base comprises fatty acid, generally stearic acid or a combination thereof with palmitic acid. Fatty acid, when present is preferably from 0.5 to 30% by weight, more preferably from 1 to 25% by weight and most preferably from 5 to 20% by weight of the cosmetic composition. The vanishing cream base also comprises salts of fatty acids, generally alkali metal soap, which acts as the emulsifier. The emulsifier is important for physical stability of the product. The soap is formed by in-situ neutralization of a portion of the fatty acid with caustic potash or any other base. 
     Fatty alcohols having from 10 to 30 carbon atoms are another useful category of cosmetically acceptable carrier. Illustrative of this category are stearyl alcohol, lauryl alcohol, myristyl alcohol and cetyl alcohol. Humectants of the polyhydric alcohol-type can be employed as cosmetically acceptable carriers. Typical polyhydric alcohols include glycerol, polyalkylene glycols and more preferably alkylene polyols and their derivatives, including propylene glycol, dipropylene glycol, polypropylene glycol, polyethylene glycol and derivatives thereof, sorbitol, hydroxypropyl sorbitol, hexylene glycol, 1,3-butylene glycol, isoprene glycol, 1,2,6- hexanetriol, ethoxylated glycerol, propoxylated glycerol and mixtures thereof. The amount of humectant may range anywhere from 0.5 to 50%, preferably between 1 and 15% by weight of the composition. 
     The cosmetic compositions of the present invention may be in any form. These forms may include lotions, creams, roll-on formulations, sticks, mousses, aerosol and non-aerosol sprays. 
     Surfactants, other than soap, may also be present in personal care composition of the present invention. Total concentration of the surfactant when present may range from 0.1 to 40%, preferably from 1 to 20%, optimally from 1 to 5% by weight of the composition. The surfactant may be selected from the group consisting of anionic, nonionic, cationic and amphoteric actives. Particularly preferred nonionic surfactants are those with a C10-C20 fatty alcohol or fatty acid hydrophobe condensed with from 2 to 100 moles of ethylene oxide or propylene oxide per mole of hydrophobe; C2-C10 alkyl phenols condensed with from 2 to 20 moles of alkylen oxide; mono-and di-fatty acid esters of ethylene glycol; fatty acid monoglyceride; sorbitan, mono-and di-C8-C20 fatty acids; and polyoxyethylene sorbitan as well as combinations thereof. Alkyl polyglycosides and saccharide fatty amides (e.g. methylgluconamides) are also suitable nonionic surfactants. Preferred anionic surfactants include soap; alkyl ether sulfates and sulfonates; alkyl sulfates and sulfonates; alkylbenzene sulfonates; alkyl and dialkylsulfosuccinates; C8-C20 acyl isethionate; C8-C20 alkyl ether phosphates; C8-C20 sarcosinates; and combinations thereof. 
     The cosmetic composition preferably comprises a sunscreen. The sunscreen may be organic or inorganic. It is preferred that the sunscreen is an organic sunscreen. Some examples of organic sunscreens include ethylhexyl-p-methoxycinnamate, available as Parsol MCX™; Avobenzene™, available as Parsol 1789™ ; and benzophenone-3, also known as Oxybenzone™. Inorganic sunscreen may be employed such as microfine titanium dioxide; zinc oxide; polyethylene; and various other polymers. 
     Amounts of the sunscreen agents when present may generally range from 0.1 to 30%, preferably from 2 to 20%, optimally from 3 to 10% by weight of the composition. 
     Preservatives can desirably be incorporated into the cosmetic compositions of this invention to protect against the growth of potentially harmful microorganisms. Suitable traditional preservatives for compositions of this invention are alkyl esters of para-hydroxybenzoic acid. Other preservatives which have more recently come into use include hydantoin derivatives, propionate salts, and a variety of quaternary ammonium compounds. Cosmetic chemists are familiar with appropriate preservatives and routinely choose them to satisfy the preservative challenge test and to provide product stability. Particularly preferred preservatives are phenoxyethanol, methyl paraben, propyl paraben, imidazolidinyl urea, sodium dehydroacetate and benzyl alcohol. The preservatives should be selected having regard for the use of the composition and possible incompatibilities between the preservatives and other ingredients in the emulsion. Preservatives are preferably employed in amounts ranging from 0.01% to 2% by weight of the composition. 
     The cosmetic composition preferably comprises a vitamin. Illustrative vitamins are Vitamin A (retinol), Vitamin B2, Vitamin B3 (niacinamide), Vitamin B6, Vitamin C, Vitamin E and Biotin. Derivatives of the vitamins may also be employed. For instance, Vitamin C derivatives include ascorbyl tetraiso palmitate, magnesium ascorbyl phosphate and ascorbyl glycoside. Derivatives of Vitamin E include tocopheryl acetate, tocopheryl palmitate and tocopheryl linoleate. DL-panthenol and derivatives may also be employed. 
     The total amount of vitamins, when present, in compositions according to the present invention may range from 0.001 to 10%, preferably from 0.01% to1%, optimally from 0.1 to 0.5% by weight of the personal care composition. 
     Desquamation promoters may be present. Illustrative are the alpha-hydroxycarboxylic acids and beta-hydroxycarboxylic acids. The term “acid” is meant to include not only the free acid but also salts and C1-C30 alkyl or aryl esters thereof and lactones generated from removal of water to form cyclic or linear lactone structures. Representative alpha-hydroxy acids are glycolic, lactic and malic acids. Salicylic acid is representative of the beta-hydroxycarboxylic acids. Amounts of these materials when present may range from 0.01 to 15% by weight of the composition. 
     Colorants, opacifiers and abrasives may also be included in compositions of the present invention. Each of these substances may range from 0.05 to 5%, preferably between 0.1 and 3% by weight of the composition. 
     The composition of the invention may comprise a conventional deodourant base as the cosmetically acceptable carrier. By a deodorant is meant a product in the stick, roll-on, or propellant medium which is used for personal deodorant benefit e.g. application in the under-arm or any other area which may or may not contain anti-perspirant actives. 
     Deodorant compositions can generally be in the form of firm solids, soft solids, gels, creams, and liquids and are dispensed using applicators appropriate to the physical characteristics of the composition. 
     Deodorant compositions which are delivered through roll-ons generally comprise a liquid carrier. Such liquid carrier can be hydrophobic or comprise a mixture of both hydrophilic and hydrophobic liquids. They may be in the form of an emulsion or a microemulsion. The liquid carrier or mixture of carriers often constitutes from 30 to 95% and in many instances from 40 to 80% by weight of the composition. 
     The compositions of the present invention can comprise a wide range of other optional components. The CTFA Cosmetic Ingredient Handbook, Second Edition, 1992, which is incorporated by reference herein in its entirety, describes a wide variety of non-limiting cosmetic and pharmaceutical ingredients commonly used in the skin care industry, which are suitable for use in the compositions of the present invention. Examples include: antioxidants, binders, biological additives, buffering agents, colorants, thickeners, polymers, astringents, fragrance, humectants, opacifying agents, conditioners, exfoliating agents, pH adjusters, preservatives, natural extracts, essential oils, skin sensates, skin soothing agents and skin healing agents. 
     The compositions of the present invention can also be, optionally, incorporated into an insoluble substrate for application to the skin such as in the form of a treated wipe. 
     According to another aspect of the present invention there is provided use of the cosmetic composition of the invention for skin lightening. The use is preferably for non-therapeutic applications. 
     According to yet another aspect of the present invention there is provided a method of lightening skin comprising the step of applying an effective amount of the cosmetic composition of the invention for lightening of skin. 
    
    
     EXAMPLES 
     The invention will now be demonstrated with examples. The examples are for the purpose of illustration only and do not limit the scope of the invention in any manner. 
     Test Protocols 
     Keratinocyte Differentiation Assay 
     This is an in vitro cell culture based assay to evaluate the capability of these actives to alter cell differentiation process. Keratinocytes (HaCaT cells—5×10 4  cells/well) were grown in 24 well plates for 24 hours. These proliferating keratinocytes were further cultured with actives for 24 hours. Cells were then washed with PBS and stained with acridine orange in PBS (Sigma Chemical Co, USA). Cells were washed 15 minutes later and viewed using an epi-fluorescent microscope (Olympus BX 50), at 20× magnification, using appropriate excitation and barrier filters, to simultaneously view red and green fluorescence (excitation: 460 nm and emission &gt;515 nm). The entire plate was scanned and the percentage of differentiated keratinocytes (cells with red fluorescence evenly distributed within the cytoplasm) was estimated. Data were represented as % of control. Higher % values indicate increased cell differentiation. The efficacy of various substances in the cell differentiation assay is tabulated below. 
     
       
         
           
               
             
               
                 TABLE 1 
               
             
            
               
                   
               
               
                 Results of cell differentiation assay 
               
            
           
           
               
               
               
               
            
               
                   
                 Substance 
                 Concentration 
                 % Differentiation 
               
               
                   
                   
               
               
                   
                 Sodium acetate 
                  0.01% 
                 168 
               
               
                   
                 Potassium acetate 
                  0.01% 
                 253 
               
               
                   
                 Magnesium acetate 
                  0.01% 
                 237 
               
               
                   
                 Sodium acetate 
                 0.002% 
                 175 
               
               
                   
                 Potassium acetate 
                 0.002% 
                 250 
               
               
                   
                 Magnesium acetate 
                 0.002% 
                 250 
               
               
                   
                 Ammonium acetate 
                 0.002% 
                 175 
               
               
                   
                 Control 
                 — 
                 100 
               
               
                   
                 Na tartarate (c4) 
                  0.01% 
                 165 
               
               
                   
                   
               
            
           
         
       
     
     From the above table it is clear that potassium and magnesium acetate provide for better efficacy in keratinocyte differentiation assay as compared to similar salts of low molecular weight carboxylic acids. 
     Preparation of Compositions 
     Aqueous phase was prepared by adding potassium hydroxide, titanium dioxide, KOH, methyl paraben, and disodium EDTA. The aqueous phase was heated till 75° C. and stearic acid melted at temperature of 75° C. was added to it, followed by addition of the remaining oil phase ingredients (cetyl alcohol, isopropyl myristate, Parsol 1789, Parsol MCX and dimethicone) preheated at 75° C. The emulsion was homogenized till a milky white continuous mixture is obtained. The magnesium acetate adduct was added to the emulsion after it cooled to a temperature of about 60° C. After the mixture is cooled to 35° C., the other ingredients (vitamins, perfume) are added. 
     Preparation of Magnesium Acetate Adduct 
     1 g of magnesium acetate was dissolved in 10 g of water and to this solution 2 g of polymer (Aculyn 33) was added in a homogenizer over 5 minutes followed by slow addition of 10 mL of 10% potassium hydroxide solution to obtain magnesium acetate adduct in a viscous gel format. Magnesium acetate adduct is then added to the cream formulation after emulsification is complete. The composition of the cream after addition of magnesium acetate adduct is given below 
     
       
         
           
               
             
               
                 TABLE 2 
               
             
            
               
                   
               
               
                 Cosmetic composition 
               
            
           
           
               
               
               
            
               
                   
                 Ingreient 
                 % by weight 
               
               
                   
                   
               
            
           
           
               
               
               
            
               
                   
                 Water 
                 53 
               
               
                   
                 stearic acid 
                 18 
               
               
                   
                 Cetyl alcohol 
                 0.5 
               
               
                   
                 Isopropyl myristate 
                 0.75 
               
               
                   
                 Parsol 1789 
                 0.48 
               
               
                   
                 Parsol MCX 
                 0.75 
               
               
                   
                 Glycerine 
                 1.000 
               
               
                   
                 KOH 
                 0.97 
               
               
                   
                 Dimethicone(DC200) 
                 0.5 
               
               
                   
                 Magnesium Acetate ADDUCT 
               
               
                   
                 Aculyn 33 
                 2.000 
               
               
                   
                 KOH 10% Solution 
                 10.000 
               
               
                   
                 Magnesium Acetate 
                 1.000 
               
               
                   
                 Water 
                 10.000 
               
               
                   
                 Minors (perfume, preservatives and others) 
                 Balance 
               
               
                   
                   
               
            
           
         
       
     
     Effect of Type of Polymer on Composition Consistency: 
     The cosmetic compositions were prepared using various polymers (at the same concentration as Aculyn 33) as tabulated below along with the results in terms of formulation consistency. 
     
       
         
           
               
             
               
                 TABLE 3 
               
             
            
               
                   
               
               
                 Effect of type of polymer on composition consistency 
               
            
           
           
               
               
               
            
               
                   
                 Adduct 
                 Composition 
               
               
                 Polymer 
                 form 
                 consistency 
               
               
                   
               
               
                 Aculyn 33 
                 Gel 
                 Thick paste 
               
               
                 Polyacrylic acid (mol wt 300000) 
                 Gel 
                 Thick paste 
               
               
                 Polyethylene oxide (mol wt 100000) 
                 Gel 
                 Thick paste 
               
               
                 Poly vinyl alcohol (mol wt 100000) 
                 Gel 
                 Thick paste 
               
               
                 Poly vinyl pyrrolidone (mol wt 300000) 
                 Gel 
                 Thick paste 
               
               
                 Sodium carboxy methyl cellulose 
                 Gel 
                 Phase separation 
               
               
                 Polyacrylic acid (mol wt 100000) 
                 — 
                 Phase separation 
               
               
                 No polymer 
                 — 
                 Phase separation 
               
               
                   
               
            
           
         
       
     
     From the results it is clear that the compositions comprising magnesium acetate and specific polymers according to the present invention result into formulations with acceptable consistency without causing phase separation. 
     Human Volunteer Studies 
     A trial was carried out for 10 days with 16 volunteers. The trial consisted of the procedure as described below: 
     The tests were carried out using the cosmetic composition given in Table 2 along with a control composition which was identical in all respects to the composition of Table 2 except that the control did not comprise magnesium acetate. A specific portion of the volunteer&#39;s forearm was marked out and the compositions were applied (3 mg/cm 2 ) five times daily in about equal intervals of time. The skin lightening score was measured by expert assessors using a colour ruler on a scale of 1 to 10. The data in Table below summarizes the average skin lightening score that is the change in skin colour with respect to the initial skin colour. A more negative score indicates a higher degree of skin lightening. A more positive score indicates skin darkening. No incidence of skin irritation or erythema was reported. Spreading characteristics and sensory feel of both the compositions were acceptable to the volunteers. 
     
       
         
           
               
             
               
                 TABLE 4 
               
             
            
               
                   
               
               
                 Skin lightening efficacy in human volunteer studies 
               
            
           
           
               
               
               
               
            
               
                   
                 Composition 
                 Skin Lightening 
                 % Responders 
               
               
                   
                   
               
               
                   
                 Control 
                 −0.29 
                 88 
               
               
                   
                 Composition of Table 2 
                 −0.35 
                 94 
               
               
                   
                   
               
            
           
         
       
     
     From the results, it is clear that the composition according to the present invention provides a significant skin lightening (P&lt;0.10 significance) benefit. 
     It will be appreciated that cosmetic composition according to the present invention provides relatively more efficacious skin lightening and has relatively better spreading characteristics and acceptable sensory feel.