FORM - 2
THE PATENTS ACT, 1970
(39 of 1970)
&
The Patents Rules, 2006
PROVISIONAL SPECIFICATION
(See Section 10 arid Rule 13)


A COSMETIC COMPOSITION
HINDUSTAN UNILEVER LIMITED, a company incorporated under
the Indian Companies Act, 1913 and having its registered office
at 165/166, Backbay Reclamation, Mumbai -400 020, Maharashtra, India
The following specification describes the invention


TECHNICAL FIELD
The present invention relates to a cosmetic composition for skin lightening.
BACKGROUND AND PRIOR ART
Consumers, particularly from Asia, prefer a lighter skin colour and therefore skin lightening has been an active area of research in the past. Skin lightening agents used in the past have undesirable side effects and/or are either 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.
US4425329 (Kao Soaps, 1984) describes a water-in-oil type cosmetic composition comprising a cosmetic oil base material, water and a specific emulsifier with the specific emulsifier comprising the following three components: (1) 94 to 43% by weight of alpha -mono(methyl-branched afkyl) glyceryl ether represented by the formula (I): R-OCH2CH(OH)CH20H (I) where, R is a methyl-branched saturated hydrocarbon group having 14 to 20 carbon atoms; (2) 0.4 to

9.8% by weight of a multivalent metal salt of a saturated or unsaturated aliphatic acid having 10 to 22 carbon atoms; and (3) 8 to 54% by weight of at least one inorganic or organic salt having a solubility in water of at least 0.2 g per 100 g of water at 20 °C.
US6495602 (Bradley Pharmaceuticals, 2002) describes compositions of a novel astringent and keratolytic topical pharmaceutical base into which drugs can be incorporated such as for example an anti-pruritic drug and/or an anti¬inflammatory drug. The compositions are said to comprise 0.01-1% astringent.
US2004037766 (Kligerman et al ,2004) describes a skin treatment composition containing ionic calcium and a dermatologically acceptable water-soluble, water-miscible or water-based carrier for treating a skin condition in a mammal, such as dry skin, dry scalp, a burn, sunburn, irritation or minor wound. The ionic calcium is said to be preferably present as the water soluble calcium glycerophosphate salt.
US2005123620 (Chou Consultants Inc, 2005) describes a method for treatment of acne and warts, by topically applying an effective amount of one or more polyvalent metal compounds.
The prior art does not have specific disclosure of compositions comprising salts of C2-C3 acids for the purpose of skin lightening.
Present inventors have surprisingly found that salts, and earth metal salts of C2-C3 carboxylic acid provide efficacious skin lightening when incorporated in a cosmetic composition at a certain range.
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 carboxylic acid having from 2 to 3
carbon atoms, 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.
Salt of a carboxylic acid having from 2 to 3 carbon atoms 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 a salt of a carboxylic acid having from 2 to 3 carbon atoms. Preferably the carboxylic acid sait is of ammonium, sodium, potassium, magnesium or calcium. More preferably, the salt is of potassium, magnesium or calcium. Magnesium and potassium salts are further preferred and magnesium salt is particularly preferred.
The carboxylic acid has preferably 2 to 3 carbon atoms and more preferably 2 carbon atoms. Acetic acid and propionic acid are preferred carboxylic acids with acetic acid being particularly preferred.
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. It is particularly preferred that the cosmetic composition comprises the polymer when the composition comprises calcium or magnesium salt of a carboxylic acid having from 2 to 3 carbon atoms.
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 aikyl 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/C 10-30 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 salt of C2 or C3 carboxylic acid and an aqueous solution are preferably premixed together to form an adduct prior to adding to the composition.
Cosmetically acceptable carrier
Compositions of this invention comprise a cosmetically acceptable carrier. Amount of the carrier can be upto 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 personal care 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 personal care composition.
Fatty acids having from 10 to 30 carbon atoms are also suitable as cosmetically acceptable carriers. Illustrative of this category are pel^rgonic, 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 can)posti)or>. 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; alkyi 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 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.
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
Keratinocvte 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 X 104 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 20X magnification, using appropriate excitation

and barrier filters, to simultaneously view red and green fluorescence (excitation: 460 nm and emission > 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 salts of C2 acids have better efficacy as compared to salts of longer chain C4 acids. Further, it is clear that potassium and magnesium salts have better efficacy as compared to sodium or ammonium salts.
Preparation of the formulations
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 is homogenized till a milky white continuous mixture is obtained. The

magnesium acetate adduct was added to the emulsion after it cools to the temperature of 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 emulsific^tion 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
IsoPropylMyristate 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 as tabulated below along with the results in terms of formulation consistency.
Table 3: Effect of type of polymer on composition consistency

Polymer Adduct form Composition 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's forearm was marked out and the compositions were applied (3 mg/cm2) 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 < 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.