Title of Invention


Abstract A cosmetic skin care composition comprising : (i) an organic solvent extract of chick pea in an amount of from 0.00001 to 10 wt.% (ii) a retinoid selected from retinol and retinyl esters in an amount of from 0.001 to 10 wt.% ; and (iii) a cosmetically acceptable vehicle.
Full Text FORM2
(39 of 1970)
(See section 10; rule 13)
Title of the invention
HINDUSTAN LEVER LIMITED, a company incorporated under the Indian Companies Act, 1913 having its registered office at Hindustan Lever House, 165/166, Backbay Reclamation, Mumbai-400 020, State of Maharashtra, India
The following specification describes the nature of this invention (and the manner in which it is to be performed)

The present invention relates to cosmetic compositions containing chick pea extract in combination with retinoids and to methods of conditioning skin by the application of such compositions to the skin.
Retinol (vitamin A) is en endogenous compound which occurs naturally in the huraan body and is essential for normal epithelial cell differentiation. Natural and synthetic vitamin A derivatives have been used extensively in the treatment of a variety of skin disorders and as skin repair and renewal agents. P.etinoic acid has been used to treat a variety of skin conditions such as acne, wrinkles, psoriasis, age spots and skin discoloration.
Within the cells, retinol and retinoic acid are bound to specific cellular binding proteins, two of the major proteins are CRA3P-1 and -2 (Roos ec el., Pharmacological reviews: 50, 315-333, -1993). These proteins act in reculatinc the intracellular concentration of retinoids by acting as both storage or shuttle proteins in retinoid metabolism. The levels cf this protein are regulated by the amount of cf retinoic acid within the cells. Higher cellular

levels of retinoids increase the expression cf CRAEP-2. Therefore, the amount of this protein in the ceils, is a measure of the retinoid activity cf the cells. Skin cells contain CRABP-2 both in the epidermis and the dermis. CRA3P-2 response to retinoid administration in fibroblasts in. vitro is used as a reproducible measure cf retinoid bicactivity that predict human skin responses (Elder et al., J.' Invest. Dermatol., 106: 517-521, 1996). Therefore, CRABP-2 expression of fibroblasts is a measure cf retinoid activity leading to various cosmetic skin benefits (antiaging, anti wrinkling, skin conditioning etc.;.
Chick pea or Spanish pea (Cicer ariezinum) , a common dietary lentil, contains flavonoids including daidzein, formononetin, biochanin A, pratensein, homcferreirin, medicarpin, maackiain, methyl coumestrol, medicagol, fonr.ononetin giucoside and biochanin A glucoside (Ingham et al., In: Progress in the chemistry of Organic natural products, vol 43: Ed-W. Herz et al., Springer-Verlag, Wien, New York, 1983) . Flavonoids derived from chick pea have beer, reported to have lipid lowering effects in the blood and liver of rats. Several nutritional studies report on protein derived from chick pea for use as nutritional supplements and ways to improve the protein quality of chick pea. Vasiliou, US patent 4,761,285 discloses the use of chick peas as a dietary supplement or for internal or topitai treatment of haemorrhoids. In India, a cosmetic mask cr skin treatment made from chick pea powder .-.ixec with water is a common beauty treatment.

The present invention is based in part on the discovery that the organic solvent chick pea extract in corbination with retinoids enhances CRA8P-2 expression in fibroblasts.
The present invention relates to a cosmetic skin care
composition comprising:
(i) an organic solvent extract of chick pea in an amount
of from 0.00001 to 10 wt. %; (ii) a retinoid in an amount of from 0.001 to 10 wt.%; and (iii) a cosmetically acceptable vehicle.
The present invention also includes a method of improving or preventing the condition of wrinkled, lined, dry, flaky, aged or photodamaged skin and improving skin thickness, elasticity,. flexibility, radiance, glow and plumpness, which method includes applying the inventive composition to the skin. Compositions of the invention are intended for topical application to mammalian skin- which is already dry, flaky, lined, wrinkled, aged, photodamaged, or may be applied prophylactically to reduce the deteriorative changes.
Except in the examples, or where otherwise explicitly indicated, all numbers in this description indicating amounts of xaterial or conditions of reaction, physical properties of materials and/or use are to be understood as modified by the

word "about." All amounts are by weight of the composition, unless otherwise specified.
Chick peas are suitable for use in the ir.ver.tive compositions in the form of an organic extract. The chick oea extract is prepared for use in the present invention from dried chick peas. Dried chick peas may be obtained from Arrowhead Mills, from health food stores or supermarkets.
The organic chick pea extracts are prepared by extracting the dried chick peas with a solvent by stirring 1 part cf dried chick peas with 2 to 5 parts of the solvent for from 4 to 24 hours at room temperature. Suitable solvents are described below. The extracts are clarified by filtration and/or centrifugation, then dried by evaporation (optionally, under vacuum) to obtain the organic chick pea extract.
Solvents suitable for the preparation of chick pea extract
for use in the present invention include, but are not limited
to: ethanol, methanol, hexane, chloroform, dichloromethar.e
and ethyl acetate. Preferred solvents are dichicromethane,
methanol, or ethanol in order to- optimize activity. The
extract may be further concentrated,' fractioned, re-extracted
or purified, e.g. by organic sclvent extraction or by
In general, the amount of the chick pea extract in. the inventive ccmocsiticr.s is in the range of from C.0QQC1*. to 10? by weight composition. Preferably in order tc icv.'5r cost and maximize the effect, the amount ci chick ess.

extract is in the range of from 0.01 to 10% and most preferably is in the range of from 0.1% to 5% by wt. of the composition.
The inventive compositions further comprise a retinoid selected from retinol or retinyl ester. The term "retinol" includes the following isomers of retinol: all-trans-retir.ol, 13-cis-retinol, 11-cis-retinol, 9-cis-retinol, 3,4-didehydro-retinoi. Preferred isomers are all-trans-retinol, 13-cis-retinoi, 3,4-didehycro-retinol, S-cis-retinoi. Most preferred is all-trans-retinol, due to its wide commercial availability.
Retinyl ester is an ester cf retinol. The term "retinol" has been defined above. Retinyl esters suitable for use in the present invention are C1-C30 esters of retinol, preferably C2-C20 esters, and most preferably C2C3, and C is esters because they are. more commonly available. Examples of retinyl esters include but are not limited to: retinyl pal.T.itate, retinyl formate, retinyl acetate, retinyl propionate, retinyl butyrate, retinyl valerate, retinyl isovalerate, retinyl hexanoate, retinyl heptanoate, retinyl octanoate, .retinyl nonancate, retinyl decanoate, retinyl undecandate, retinyl iaurate, retinyl tridecanoate, retinyl myristate, retinyl pentadecanoate, retinyl heptadeconoate, retir.yi stearate, retinyl isostearate, retinyl nonadecanoate, retir.yi arachidcnate, retir.yi benenate, retinyl linoleate, ret-.-yi oleate.
The -referred ester for use' in the present invention is seierted from retinyl palrr.itate, retinyl acetate and retinyl

propionate, because these are the most commercially available and therefore the cheapest. Retinyl linoieate is also preferred due to its efficacy.
Retinol or retinyl ester is employed in the inventive composition in an amount of from about 0.001% to about 10%, preferably in an amount of from about 0.01% to about 1%, most preferably in an amount of from about 0.01% to about 0.5% by wt. of the composition.
The composition also comprises a cosmetically acceptable vehicle to act as a diluant, dispersant or carrier for the chick pea extract and the retinoid in the composition, so as to facilitate their distribution when the composition is applied to the skin.
Vehicles other than, or in addition to, water can include liquid or solid emollients, solvents, humectants, thickeners and powders. An especially preferred nonaqueous carrier is a polydimethyl siloxane and/or a polydirnethyl phenyl siloxane. Silicones of this invention may be those with viscosities ranging anywhere from about 10 to 10,000,000mm2/s(centistokes) . at. 25°C. Especially desirable are mixtures of low and high viscosity silicones. These silicones are available from the General Electric Company under trademarks Vicasil, SE and ST and from the Dow Corning Company under the 200 and 550 Series. Amounts cf silicone which can be utilized in the compositions of this invention range anywhere from 5% to S5%, preferably from 25% to 90% by weight of the composition.

The cosmetically acceptable vehicle will usually comprise from 5% co 99,9%, preferably from 25% to 80% by weight of the composition, and can, in the absence cf other cosmetic adjuncts, form the balance cf the composition. Preferably, the vehicle is at least 80 wt. % water, by weight of the vehicle. Preferably, water comprises at least 50 wt.% of the inventive composition, most preferably from 60 to 80 wt.%, by weight of the composition.
Optional Skin Benefit Materials and Cosmetic Adjuncts
An oil or oily material may be present, together with an emulsifier to provide either a water-in-oii emulsion or an oil-in-water emulsion, depending largely on the average hydrophilic-lipophilic balance (HL3) of the emulsifier employed.
The compositions of the present invention preferably include sunscreens. Sunscreens include those materials commonly employed to block ultraviolet light. Illustrative compounds are the derivatives of ?ABA, cinnamate and salicylate. For example, octyl methoxycinnamate and 2-hydroxy-4-methoxy benzophenone (also known as oxybenzone) can be used. Octyl methoxycinnamate and 2-hydroxy-4-met'hoxy benzophenone are commercially available under the trademarks, Parsoi MCX and 3enzophenone-3, respectively. The exact amount cf sunscreen employed in the emulsions may vary depending upon the degree of protection desired from the sun's UV radiation.
Emollients may also be incorporated into cosmetic compositions cf the present invention. Levels of such

emollients may range from 0.5% to 501, preferably between 5% and 30% by weight of the total composition. Emollients may be classified under such general chemical categories as esters, fatty acids and alcohols, poiyols and hydrocarbons.
Esters may be mono- or di-esters. Acceptable examples of fatty di-esters include dibutyl adipate, diethyl sebacate, diisopropyl dimerate, and dioctyl succinate. Acceptable branched chain fatty esters include 2-ethyl-hexyl myristate, isopropyl stearate and isostearyl palmitate. Acceptable tribasic acid esters include triisopropyi trilinoieate and trilauryl citrate. Acceptable straight chain fatty esters include lauryl palmitate, myristyl lactate, and stearyl oieate. Preferred esters include coco-caprylate/caprate (a blend of coco-caprylate and coco-caprate), propylene glycol myristyl ether acetate, diisopropyl adipate and cetyl octanoate.
Suitable fatty alcohols and acids include those compounds having from 10 to 20 carbon atoms. Especially preferred are compounds such as cetyl, myristyl, palmitic and stearyl alcohols and acids.
Awocvg the polyoLs which may serve as emoliier.ts ere Linear and branched chain aikyl poiyhydroxyi compounds. For example, propylene glycol, sorbitol and glycerin are oreferred. Also useful may be polymeric poiyols such as poly-propylene glycol and polyethylene glycol. Butyiene and cropyiene glycol are also especially preferred as oenetraticn enhancers.

Exemplary hydrocarbons which may serve as emollients are those having hydrocarbon chains ranging anywhere from 12 to 30 carbon atoms. Specific examples include mineral oil, petroleum jelly, squalene and iscparaffins.
Another category of functional ingredients within the cosmetic compositions of the present invention are thickeners. A thickener will usually be present in amounts anywhere from 0.1 to 20% by weight, preferably from about 0.5% to 10% by weight of the composition. Exemplary thickeners are cress-linked polyacrylate materials available under the trademark Carbcpoi from the 3.F. Goodrich Company. Gums may be employed such as xanthan, carrageenan, gelatin, karaya, pectin and locust beans gum. Under ' certain circumstances the thickening function may be accomplished by a material also serving as a silicone or emollient. For instance, silicone gums in excess of 10 centistokes and esters such as glycerol stearate have dual functionality.
Powders may• be incorporated into the cosmetic compositions of the present invention. These powders include chalk, talc, kaolin, starch, smectite clays, chemically modified magnesium aluminum silicate, • organically modified montrr.orilionite clay, hydrated aluminum silicate, fumed silica, aluminum starch octenyl succinate and mixtures thereof.
Other adjunct minor components may also be incorporated into the cosmetic cempositions. These ingredients may include coloring agents, ocacifiers and perfumes. Amounts cf these

other adjunct minor components may range anywhere from 0.001% up to 20% by weight of the composition.
Use of the Composition
The composition according to the invention is intended primarily as a product for topical cosmetic application to human skin, especially as an agent for conditioning, moisturizing and smoothening the skin, and preventing or reducing the appearance of lined, wrinkled or aged skin.
In use, a small quantity of the composition, fc'r example from 1 to 100ml, is applied to exposed areas of the skin, from a suitable container or applicator and, if necessary, it is then spread over and/or rubbed into the skin using the hand or fingers or a suitable device.
Product Form and Packaging
The topical skin treatment compositions of the present invention may be formulated as a lotion, a cream or a gei. The composition may be packaged in a suitable container to suit its viscosity and intended use by the consumer. For example, a lotion or cream may be packaged in a bottle or a roll-ball applicator, or a propellant-criven aerosol device or a container fitted with a pump suitable for finger ODeration. When the composition is a cream, it may,simply be stored in a non-deformable bottle or squeeze container, such as a tube or a lidded jar. The composition may also be included in capsules such as those described in 'J. S. Patent incorporated herein by reference. The invention

accordingly also provides a closed container con-aining a cosmetically acceptable composition as herein defined.
The following specific examples further illustrate the invention, but the invention is not limited thereto. In all examples, chick pea was obtained from local supermarkets. Retinoids were obtained from Sigma. The student t-test was used to calculate all p-values.
The following methods were employed:
1. Preparation of chick pea extracts:
Dried chick peas were purchased from local supermarkets and powdered in a dry grinder. An alcoholic extract of the chick peas was prepared by stirring 1 gram of the dry chick pea powder in 10 ml of sthanol for 4 to 24 hrs at room temperature. The extract was clarified by filtration and centrifugation, to obtain a 10% extract of chick pea in ethanol.
2. Cell culture method: Humars adult fibroblasts obtained from sun-protectec inner arm of 25-30 old year female volunteers were used. Cells were grown in 1:1 DMEM/Hams F12 media containing -10% FBS,
mai.-.tainec at 37'C in a 5* CO2 atmosphere under normal
atmospheric oxygen tension. Third passage adult fibroblasts

were grown in DMEM media with 10% F3S in 12-well plates at a seeding density cf 40,000 cells/mi/well. The cells at 80% confluence were- rinsed in serum free and phenol red free (PRF) DMEM media twice. Pre-treatment with chick pea extract for 4 hours was conducted and then dosed with retinoids and was incubated for 43 hours. After incubation, the wells were washed twice with IX P3S and the cell monolayer was harvested in 100ul ceil lysis buffer (contains IX PBS, 1% TritonX, 0.5% sodium deoxycholate, 0.1% SDS containing protease inhibitor (10mg/ml PMSF in isopropanol, 10u/ml) ) . The suspension was spun at 14000rpm for 10 minutes, the supernatant collected and an aliquot of the supernatant used for protein quantification. The protein concentration was determined using a Pierce protein kit. The remainder of the lOOul supernatant (cell iysate) was denatured in a mixture of 40ul sample buffer (NOVEX) and 0.5% 3eta mercaptoechanol (BME) by boiling the sample for 5 minutes. Equal amounts of protein was then loaded onto 16% Tris-glycine gels for protein analysis by SDS page and Western Immuno-blotting for CRABP-2 protein expression.
3. Detection of Cellular Retinoic Acid Binding Protein 2 (CRA3P-2) in fibroblasts:
In order to measure the levels of CRABP-2 in the fibroblasts prepared as described above, the cell supernatant was re-suspended in 4X sample buffer anz 0.5% BME, boiled for 5 minutes and used for western blotting. Equal amounts of protein were loaded onto 16% Tris-glycine gels for CRABP-2 protein analysis by SDS page and Western Immuno-blotting. The gels were transferred to nitrocellulose blots and Western Blotting was carried out using ncnoclonai antibodies

to CRA3F-2 according to standard procedures. The CRABF-2 protein band was visualized in the Western 3iots using the chemilumir.escence system obtained from Santa Cruz Biotechnology (SantaCruz, CA) . The bends in the film were quantitated by densitometric scanning, the data' from triplicate samples were calculated as % of control and expressed in the following tables as % increase over control (with control as 100%) +/-SD of triplicates.
The,examples investigated the effect en CRA3P-2 expression of fibroblasts of combinations of various concentrations of chic! pea extract and retinoids.
EXAMPLE 1: 100 nM retinoids and 0.lul of a 10% chick pea extract

EXAMPLE 2: 100 nM retinoids and 1.0 v.1 of a 10% chick pe extract

EXAMPLE 3: 500 r.M retinoids and 0.1 pi of a 10% chick pea extract

EXAMPLE: 4: 500 nM retinoids and 1.0 ul of a 101 chick extract:

The results summarized in Examples 1-4 demonstrate that retinoids at some concentrations synergize with chick pea extract at some concentrations. Optimum synergy was observed with ail the retinoids at 500 nM level and 1 ul of chick pea extract.

It should be understood that the specific forms of the invention herein illustrated and described are intended to be representative only. Changes, including but not limited to those suggested in this specification, may be made in the illustrated embodiments without departing from the clear teachings of the disclosure. Accordingly, reference should be made to the following appended claims in determining the full scope of the invention.

A cosmetic skin care composition comprising :
(i) an organic solvent extract of chick pea in an amount of from 0.00001 to
10 wt.% (ii) a retinoid selected from retinol and retinyl esters in an amount of from
0.001 to 10 wt.% ; and (iii) a cosmetically acceptable vehicle.
Dated this 14th day of May 2002


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Patent Number 213387
Indian Patent Application Number IN/PCT/2002/00608/MUM
PG Journal Number 43/2008
Publication Date 24-Oct-2008
Grant Date 01-Jan-2008
Date of Filing 14-May-2002
# Inventor's Name Inventor's Address
PCT International Classification Number A61K7/48
PCT International Application Number PCT/GB0/04304
PCT International Filing date 2000-11-09
PCT Conventions:
# PCT Application Number Date of Convention Priority Country
1 60/165830 1999-11-16 U.S.A.