WO2018134714A1

WO2018134714A1 - Whitening skin care composition based on dihydromyricetin, niacinamide and a ph modifier

Info

Publication number: WO2018134714A1
Application number: PCT/IB2018/050223
Authority: WO
Inventors: Rajan Raghavachari
Original assignee: R&R Salons Pvt. Ltd.
Priority date: 2017-01-21
Filing date: 2018-01-13
Publication date: 2018-07-26

Abstract

The present subject matter provides a cosmetic skin care composition. The composition comprises dihydromyricetin, niacinamide, and a pH modifier on a cosmetically acceptable vehicle. The pH modifier is configured to adjust pH of the cosmetic composition at a level to control discoloration of the dihydromyricetin and chemical degradation of the niacinamide.

Description

WHITENING SKIN CARE COMPOSITION BASED ON DIHYDROMYRICETIN, NIACINAMIDE AND A PH MODIFIER

TECHNICAL FIELD

[001] The subject matter relates to cosmetic compositions in general.

More specifically, the subject matter relates to skin care compositions. Even more specifically the subject matter relates to compositions for skin lightening.

BACKGROUND

[002] The skin colour is primarily determined by the amount of melanin present in the skin. Melanin is a brown-black pigment present in the skin which is produced within the cells known as melanocytes which reside below or between the basal cells of the epidermis, the outermost skin layer.

[003] In recent years cosmetic compositions have been developed to reduce the amount of melanin in the skin and therefore whiten/lighten the skin by reducing or inhibiting melanogenesis or reducing hyperactive melanocytes. The development efforts have been focused on actives that inhibit the function or activity of tyrosinase or block the chain reaction at various points in the melanogenesis process.

[00 ] Solutions aiming at skin lighting generally include ingredients that may inhibit the melanin in skin by inhibiting either it's generation or it's distribution on the skin. Some of the commercially available ingredients have a number of problems. For example, some ingredients deteriorate and tend to lose it physical characteristics in a short span of time. In one possibility some ingredients may discolor and lose aesthetic charm for a user. In some other examples, the ingredients do not make a homogeneous solution and they tend to separate thus resulting in effective failure of the compositions. Some compositions fail merely because its ingredients have relatively opposing requirements, that is to say, satisfying one ingredient's requirements may lead to adversely affecting another ingredient.

[005] Therefore, there is a need to provide a composition that not only addresses the problem of discoloration or degradation but also enhances cosmetic benefits which is skin lightening in this subject matter. SUMMARY

[006] One of the desirable ingredients in a cosmetic composition may be an antioxidant. Dihydromyricetin (generally traded as telocapil™ and used interchangeably throughout this specification) is one such antioxidant. Another desirable ingredient in the cosmetic composition can be an ingredient that influences the process of melanogenesis. One such ingredient is niacinamide. While, both the ingredients are desirable, use of these two ingredients together in a single cosmetic composition is challenging because of their opposing requirements. Another ingredient that is desirable for enhancing the cosmetic effect of the cosmetic composition is derivative of resorcinol. However derivative of resorcinol, for example -butyl resorcinol, poses difficulties in solubilizing. Therefore, the ingredients such as discussed above, are though desirable, present challenges for their use in a single composition. Hence, the prior compositions employ these ingredients individually but not in a combination all three of them. [007] Now therefore, the present subject matter provides a solution that addresses above and other problems and enables employing of the ingredients that have contrary or competing requirements. The present subject matter provides a cosmetic composition comprising dihydromyricetin and niacinamide in a cosmetically acceptable vehicle. The composition is provided with a pH modifier. The pH modifier is configured to adjust pH of the cosmetic composition at a level to control discoloration of the dihydromyricetin while protecting niacinamide from significantly getting converted into nicotinic acid. In one embodiment the cosmetic composition further comprises derivative of resorcinol and polyol that is an effective solubilizer. Providing polyol not only addresses solubility challenges of derivative of resorcinol but also enhances effectiveness of the cosmetic composition as an anti-irritant ingredient. Similarly, providing pH modifier not only protects niacinamide from getting converted to nicotinic acid and discoloration of dihydromyricetin, but also enhances effectiveness of the cosmetic composition as a tyrosinase suppressor.

[008] The present subject matter provides a cosmetic skin care composition comprising: dihydromyricetin, niacinamide, and a pH modifier on a cosmetically acceptable vehicle, wherein the pH modifier is configured to adjust pH of the cosmetic composition at a level to control discoloration of the dihydromyricetin and chemical degradation of the niacinamide. According to one embodiment, the cosmetic composition is provided with the pH modifier in a concentration low enough to prevent discoloration of the dihydromyricetin and high enough to prevent chemical degradation of the niacinamide. In a second embodiment, the pH modifier is present in the composition in any one of range of: o.i- 20 wt%, 0.2- 12.0 wt% and 0.5 - 8 wt%. In a third embodiment, the pH modifier is an alpha hydroxy acid. Some examples of the alpha hydroxy acid are glycolic, malic, tartaric, lactic, citric, acetic acids etc. In a fourth embodiment, the pH modifier is glycolic acid. In a fifth embodiment, the composition has a pH in any one of the range of: 3.0-6.0, 4.0-5.5 and 4.0- 5.0. In a sixth embodiment, the dihydromyricetin is present in the composition in any one of range: 0.01-20 wt%, 0.1-5.0 wt% and 0.2-3.0 wt%. In a seventh embodiment, the niacinamide is present in the composition in any one of range: 0.1-10 wt%, 0.2-5 wt% and 0.5-3 wt%. In an eight embodiment, the cosmetic composition further comprises resorcinol. In a ninth embodiment, the resorcinol is 4-butyl resorcinol. In another embodiment, the resorcinol is present in the composition in any one of amount range of: 0.1- 10 wt%, 0.1- 5 wt% and 0.2-0.5 wt%. In a further embodiment, the composition also comprises a polyol selected from 1,3-propane diol, propylene glycol, glycerol, sorbitol, and polyethylene glycol. In yet a further embodiment, the polyol is present in the composition in any one of range of: 0.1- 30 wt%, 0.2- 20 wt% and 0.5- 16 wt%. In a yet another embodiment, the composition further comprises an agent selected from a chelating agent and an antioxidant or a combination thereof. In some embodiment, the chelating agent is selected from disodium ethylenediaminetetraacetate (EDTA), diethylenetriaminepentaacetic acid (DTPA), trisodium ethylenediaminedisuccinate (EDDS) or a combination thereof. In some other embodiment, the antioxidant is selected from sodium-bisulphite, butylated hydroxytoluene (BHT), ascorbic acid and its derivatives, tocopherol and its derivatives or a combination thereof.

BRIEF DESCRIPTION OF DRAWINGS

[009] The subject matter is now described with reference to the accompanying figures, in that: [ooio] FIG. l shows comparative graphical representation of melanin reduction resulting from a number of compositions, including the compositions of the present of the present subject matter; and

[0011] FIG. 2 and FIG. 3 show results of discoloration and stability study of a number of compositions, including the compositions of the present of the present subject matter.

DETAILED DESCRIPTION

[0012] Before the present subject matter is described in further detail, it is to be understood that the subject matter is not limited to the particular embodiments described, and may vary as such. It is also to be understood that the terminology used throughout the preceding and forthcoming discussion is for the purpose of describing particular embodiments only, and is not intended to be limiting. It must be noted that as used herein, the singular forms "a", "an", and "the" include plural references unless the context clearly dictates otherwise. [0013] Melanin (also referred as "melanin pigment" or merely "pigment") protects the body from the damaging effects of ultraviolet radiation. The exposure to sunlight or other UV radiation can stimulate the melanocytes to produce melanin. The skin colour is due to melanin pigment that skin cells generate. Melanin is dark in color. Due to dark colour of the melanin, lower amounts and concentrated distribution of melanin result in lighter skin colour while higher amounts and uniform broad dispersion of melanin result in darker skin colour. Melanin is formed through a process termed as 'melanogenesis'. There are a number of biological pathways involved in the generation of melanin and its transfer all the way to the top layer of the skin. In this process, Tyrosinase, a copper containing enzyme present in the body tissues, serves as a catalyst to oxidize amino acid tyrosine to dihydroxyphenylalanine in melanocytes. Within melanocytes, melanin is bound to a protein matrix to form melanosomes where tyrosinase converts tyrosine to eumelanin (black pigment) or phenomelanin (yellowish and reddish pigment). Melanin bio-synthesis involves chain of oxidative reactions catalysed by a series of enzymes. In addition to tyrosinase, DOPAchrometautomerase (TRP-2) and DHICA oxidase (TRP-i) proteins are responsible for converting DOPAchrome to 5,6-dihydroxy indole -2-carboxy acid which leads to the formation of eumelanin.

[001 ] In recent years cosmetic compositions have been developed to reduce the amount of melanin in the skin and therefore whiten/lighten the skin by reducing or inhibiting melanogenesis or reducing hyperactive melanocytes. The development efforts have been focused on actives that inhibit the function or activity of tyrosinase or block the chain reaction at various points in the melanogenesis process. The compositions accordingly may achieve skin whitening/lightening by blocking tyrosinase activity, reducing tyrosinase synthesis, inhibiting TRP-i and/or TRP-2, blocking melanin transfer from melanocytes to keratinocytes. Keratinocyte is predominant cell type in the epidermis -the outermost layer of the skin- constituting 90% of the cells.

[0015] Exposure to harmful UV rays, depilation and waxing processes also induce inflammation (and thus cause erythema) and irritation and thereby aggravate melanin synthesis / melanogenesis. Therefore, it is desirable that the skin lightening or cosmetic compositions not only have an ingredient that influences or affects only one pathway of melanogenesis but carry a combination of ingredients those influence or affect multiple different pathways in a synchronous manner, so that the cosmetic composition provides enhanced skin lightening benefit.

[0016] A composition for achieving desired skin color through depigmentation of skin has been one of the desirable cosmetic benefits. There are many ingredients that are desired for skin lightening effect due to their inhibitory action at various stages of melanin generation and its distribution on the skin. Some of the ingredients are used individually for slowing down the proliferation of melanocytes and keratinocytes, suppression of tyrosinase, inhibition of melanogenesis, exfoliation of dead skin cells, and also for soothing skin from stresses due to oxidation and inflammation. [0017] Niacinamide is one of the often used skin lightening ingredients, which can inhibit not only tyrosinase activity that is involved in melanin synthesis but also suppresses the transfer of melanosomes-containing-melanin from melanocyte to keratinocyte. Niacinamide is also a TRP-i inhibitor. Dihydromyricetin (telocapil™) is another ingredient that helps in achieving lighter skin colour through its antioxidant action. There are other ingredients like resorcinol and its derivations such as 4-butyl resorcinol that enhances the skin lightening benefit by inhibiting the activity of tyrosinase and tyrosinase- related-protein TRPi.

[0018] All the above mentioned ingredients though are beneficial when used individually, poses a challenge for their use in combination. Each of these ingredients has a specific chemical requirement that may not be suitable for the other ingredient. Accordingly, their combined use in a composition presents several challenges. In one such challenge niacinamide and dihydromyricetin have contradictory or opposing chemical requirements to remain effective. Dihydromyricetin requires highly acidic environment, in the absence of which it gets easily oxidized and causes discolouration of the composition. Whereas, niacinamide requires a slightly lower acidic environment (i.e. higher acidic pH) to maintain its chemical form and hence its activity. Highly acidic environment leads to conversion of nicotinamide to nicotinic acid that makes the composition less effective.

[0019] In another challenge faced is solubility of ingredients such as resorcinol and its derivative in an aqueous composition. I n one of such example resorcinol such as 4-butyl resorcinol tends to separate out from the aqueous composition (e.g. aqueous mist, gel) and thus leaving the composition not fit for use.

[0020] Accordingly, compositions may be available having any of the above ingredients individually. However a composition having a combination of any of these ingredients is a challenge to a chemist. Therefore, there is a need to provide a composition that enables use of desirable ingredients in combination. The present subject matter provides a composition which offers a suitable environment that effectively exploits benefits of the ingredient, enhances cosmetic benefit of the composition and does not have challenges discussed above and other challenges. [0021] The present subject matter provides a cosmetic composition comprising dihydromyricetin as telocapil™ and niacinamide in a cosmetically acceptable vehicle. I n the following discussions units are in wt/wt. I n an embodiment, the composition comprises telocapil in an amount of o.oi- 20 wt%. I n an example, the telocapil is present between 0.1- 5.0 wt%. In another example, the telocapil is present between 0.2-3 wt%. I n another embodiment, the composition comprises niacinamide in an amount of o.i-io wt%. In an example, the niacinamide is present between 0.2-5 wt%. In another example, the niacinamide is present between 0.5- 3 wt%.

[0022] Dihydromyricetin requires highly acidic environment, in the absence of which it easily oxidizes and causes discolouration of the composition. The discoloration of the cosmetic composition is not desirable because, it not only reduces aesthetic appeal of the cosmetic composition, but also, reduces the commercial value and may indicate deterioration of the composition. H igh acidic environment is not desirable for niacinamide. Highly acidic environment leads to conversion of niacinamide to nicotinic acid that makes the composition less suitable for use a skin care composition.

[0023] In an embodiment, the cosmetic composition provides a pH modifier. The pH modifier is configured to adjust pH of the cosmetic composition at a level to control discoloration of the dihydromyricetin and conversion of niacinamide into nicotinic acid. The "acidic pH" of the composition is low enough to prevent discoloration of the dihydromyricetin and high enough to prevent significant conversion of niacinamide into nicotinic acid. I n an embodiment, the pH modifier is an alpha hydroxyl acid. It shall become clear to a person in the art, that the pH modifier is a hydrogen ion donor. I n some embodiments, the acidifying agent may be from a class of hydroxy or carboxylic acids. I n some examples, the alpha hydroxyl acid is selected from but not limited to glycolic acid, lactic acid, tartaric acid, citric acid, malic acid and mandelic etc. In a specific example, the pH modifier is glycolic acid. In an embodiment, pH of the composition is maintained between 3.8-5.5. I n another embodiment, pH of the composition is maintained between 4 - 5.5. In yet another embodiment, pH of the composition is maintained between 4- 5-The pH modifier may be present in an amount between o.oi- 25 wt%. I n some of the embodiments, the pH modifier is present in an amount between o.i-io.o wt%. I n yet another embodiment, the pH modifier is present in an amount between 0.2- 8 wt%.

[002 ] In another embodiment, in addition to the pH modifier, the discoloration of the dihydromyricetin is controlled by using a chelating agent and an antioxidant or a combination thereof. I n another aspect, the composition comprises the chelating agent. I n some examples, the chelating agent may include disodium ethylenediaminetetraacetate (EDTA), diethylenetriaminepentaacetic acid (DTPA), trisodium ethylenediaminedisuccinate (EDDS), gluconolactone and a combination thereof. The chelating agents may be present in the composition in the range o.oi- 2 wt% and in some embodiments, 0.1- 1 wt%. In yet another aspect, the composition comprises the antioxidant. Such antioxidant undergoes oxidation instead of the inhibitor (e.g. dihyromyricetin) in the composition. The antioxidants used in the present subject matter are selected from but not limited to sodium-bisulphite, butylated hydroxytoluene (BHT), ascorbic acid and its derivatives, tocopherol and its derivatives and a combination thereof. The antioxidants may be present in the composition in the range 0.01-2 wt% and in some embodiments in the range of o.1-1 wt%.

[0025] In some of the embodiments, the composition comprises resorcinol and/or derivative of resorcinol. In an embodiment, resorcinol and/or derivative of resorcinol is present in an amount of 0.1-10 wt%. In another embodiment, the resorcinol and/or derivative of resorcinol is present in an amount between 0.1-5 wt%. In still another embodiment, the resorcinol and/or derivative of resorcinol is present in an amount between 0.2-0.5 wt%. In some embodiments, the derivative of resorcinol is -butyl resorcinol also known as a variant of kopsinol. It is observed that the kopsinol alone turns out to be cytotoxic. However, when the kopsinol used in the combination according to the present subject matter, in that kopsinol in combination with niacinamide and dihydromyricetin, the cytotoxicity of the combination dramatically reduces.

[0026] In an embodiment the resorcinol is dissolved in a solvent. I n another embodiment the solvent is a polyol. In one embodiment, the polyol is selected from but not limited to 1,3-propane diol, propylene glycol, PEG, glycerol, sorbitol, etc. In one example, the solvent used is 1,3-propane diol. In an embodiment, the polyol is present in an amount of 0.1-30 wt%. In another embodiment, the polyol is present in an amount between 0.2-20 wt%. In yet another embodiment, the polyol is present in an amount between 0.5- 16 wt%.

[0027] In another aspect the composition provided by the present subject matter also offer body and facial hair growth retardation effect.

[0028] In another aspect the composition comprises a cosmetically acceptable vehicle suitable for topical application to skin. Cosmetically acceptable vehicles are well known in the art and are selected based on the end use of the application. For example, the cosmetically acceptable vehicle of the present subject matter includes, but not limited to, those suitable for application to the skin. Such vehicles are well known to those of ordinary skill in the art, and can include one or more compatible liquid or solid filler diluents or vehicles which are suitable for application to the skin. The exact amount of a cosmetically acceptable vehicle will depend upon the level of any other optional ingredients that one of ordinary skill in the art would classify as distinct from the cosmetically acceptable vehicle (e.g., other active components). The compositions of the present subject matter preferably comprise from about 40-99 wt%, more preferably from about 70- 98 wt%, and most preferably from about 80-98 wt%, of a cosmetically acceptable vehicle.

[0029] The cosmetically acceptable vehicle and the compositions herein can be formulated in a number of ways, including but not limited to emulsions. For example, suitable emulsions include: oil-in-water, water-in-oil, water-in-oil-in-water, oil-in- water-in-oil, oil-in-water-in-silicone emulsions or other simple aqueous formulations. Desirable compositions comprise an oil-in-water emulsion and simple aqueous formulations.

[0030] The compositions of the present invention can be formulated into a wide variety of product types, including: creams, waxes, pastes, lotions, milks, mousses, gels, oils, tonics, roll-ons, serum, concentrate, and aqueous or non-aqueous sprays. Desired compositions are formulated into lotions, serum, concentrate, roll-on, creams, gels, and aqueous sprays. These product forms may be used for a number of applications, including but not limited to, hand and body lotions, cold creams, facial moisturizers, anti-acne preparations, topical analgesics, underarm roll-on, facial serum, ingrown hair concentrate, body mist/spray and the like. Any additional components required to formulate such products vary with product type and can be routinely chosen by one skilled in the art, after reading this specification.

Other Components:

[0031] The formulation also can comprise other components that may be chosen depending on the vehicle and/or the intended use of the formulation. Additional components include, but are not limited to, water soluble sunscreens (such as Eusolex 232); oil soluble sunscreens (such as octyl methoxycinnamate); and organic sunscreens (such as camphor derivatives, cinnamates, salicylates, benzophenones, triazines, PABA derivatives, diphenylacrylate derivatives, and dibenzoylmethane derivatives.); antioxidants (such as BHT); chelating agents (such as disodium EDTA); emulsion stabilizers/thickener (such as carbomer); preservatives (such as phenoxyethanol); fragrances (such as pinene); humectants/polyols (such as glycerin, sorbitol, PEG, propanediol ); polymers (such as PVP/Eicosene copolymer); water soluble film-formers (such as hydroxypropyl methylcellulose); oil-soluble film formers (such as hydrogenated C-9 Resin); moisturizing agents, such as cholesterol, sodium PCA; anionic polymers (such as xanthan gum); vitamins (such as tocopherol, and its derivatives, ascorbic acid and its derivatives etc.); inorganic particles (such as titanium dioxide, zinc oxide, su mica and silica) natural extracts (such as aloe-vera, saffron, licorice, etc.), skin lighting actives (such as, niacinamide, arbutin, kojic acid, -butyl resorcinol etc.) and the like. [0032] The compositions can also encompass one or more active components, and as such can be either cosmetic or pharmaceutical compositions. Examples of useful actives include, but are not limited to, those that improve or eradicate age spots, keratoses and wrinkles, analgesics, anesthetics, anti-acne agents, antibacterials, antiyeast agents, antifungal agents, antiviral agents, antidermatitis agents, antipruritic agents, antiemetics, antihyperkeratolytic agents, anti-dry skin agents, antiperspirants, antipsoriatic agents, antiseborrheic agents, antiaging agents, antiwrinkle agents, sunscreen agents, antihistamine agents, depigmenting agents, wound-healing agents, vitamins, corticosteroids, tanning agents or hormones. More specific examples of useful active agents include retinoids such as retinol, and esters, acids, and aldehydes thereof; ascorbic acid, and esters and metal salts thereof, tocopherol and esters and amide derivatives thereof; milk proteins; alpha- or beta-hydroxy acids; DHEA and derivatives thereof; clotrimazole, ketoconazole, miconozole, griseofulvin, hydroxyzine, diphenhydramine, pramoxine, lidocaine, procaine, mepivacaine, monobenzone, erythromycin, tetracycline, clindamycin, meclocyline, hydroquinone, minocycline, naproxen, ibuprofen, theophylline, cromolyn, albuterol, hydrocortisone, hydrocortisone 21-acetate, hydrocortisone 17- valerate, hydrocortisone 17-butyrate, betamethasone valerate, betamethasone diproprionate, triaminolone acetonide, fluocinonide, clobetasol, proprionate, benzoyl peroxide, crotamiton, propranol, promethazine, and mixtures thereof.

EXAMPLES

Example 1: Skin Lightening Body Lotion composition

[0033] The above subject matter is practiced in a body lotion composition as illustrated below in Tablei. Polyols could be one or more combination of glycerine, propylene glycol, 1,3, Propane diol. The chelating agent, antioxidant and preservative indicated below are just one of the examples in their respective category of ingredients. The example ιΑ shows the synergy between niacinamide and dihydromyricetin whereas the example ιΒ shows the avoidance of discolouration of dihydromyricetin (traded as telocapil™) by lowering the pH with the help of glycolic acid in the composition and at the same time avoiding significant conversion of niacinamide into nicotinic acid. The example IC demonstrates the enhancement of skin lightening solution with the addition of 4-butyl resorcinol and example ID demonstrates the power of 1,3-propane diol in solubilizing 4- butyl resorcinol .

Table 1

[003 ] To make 1 ton of finished body lotion product, required quantity of pasteurized demineralised water is charged to the main mixer. Phenoxyethanol followed by disodium EDTA are added and the stirring started. Then add glycerin and mix for 5 minutes. Heating is started to maintain approx. 75 deg C. Titanium dioxide is added before adding the viscous Sepiplus 400. The contents are stirred well for uniform mixing. The Octylmethoxycinnamate oil is then added once the mixer content reaches 75 deg C and recirculation is started. After 5 minutes of recirculation and ensuing homogeneity, the contents of the main mixer are cooled to below 40 deg C. Then a premix of BHT and perfume is added followed by niacinamideand glycolic acid, and having ensured the pH to be in the range of 4 to 5, then telocapil (dihydromyricetin) is added. When 4-butyl resorcinol (traded as Kopsinol) is added to the composition, it is dissolved in enough quantities of 1,3- propane diol and after ensuring complete dissolution of kopsinol, this premix is added to the main mixer. The contents are mixed well and then recirculated for 5 minutes to ensure homogeneity of the bulk before discharging the batch for packing. The total duration of the batch time is approximately 1 hour. The colour, odour, appearance, pH and density of the finished good are checked.

Example 2: Skin Lightening Facial Serum Composition

[0035] In one example, the subject matter is practiced in a facial serum composition as illustrated below in Table 2.

Table 2

[0036] To make 1 ton of skin lightening facial serum, pasteurized hot water at 75 deg C is charged into main mixer. Phenoxyethanol and glycerin are added and stirred well for 5 minutes. Thick paste of Sarasilk EL 63, Sarasense CM 56, and Sarasilk SC 86A are slowly added to the mixer in that order. The contents of the bulk are maintained at 75 deg C. The contents are recirculated for 5 minutes to ensure homogeneity of the bulk. The contents are then cooled to below 40 Deg C and a premix of BHT and perfume are added along with stirring. Sumica pearl is premixed with DM water and added to the main mixer and care is taken to ensure complete dispersion without lumps. Niacinamide and glycolic acid are premixed with DM water and this is then added to the mixer. Having ensured the pH of the bulk contents is in the range of 4 to 5, then dihydromyricetin (telocapil) is added. Kopsinol is dissolved in required quantities of 1,3- propane diol and after ensuring complete dissolution of Kopsinol, this premix is added to the main mixer. The contents are mixed well and then recirculated for 5 minutes to ensure homogeneity of the bulk before discharging the batch for packing. The total duration of the batch time is approximately 80 minutes. The colour, odour, appearance, pH and density of the finished good are checked. Polyols could be one or more combination of glycerine, sorbitol, propylene glycol, 1,3, Propane diol etc. The antioxidant and preservative indicated are just one of the examples in their respective category of ingredients and a chelating agent can also be beneficial in such a composition e.g. disodium EDTA, DTPA, TrisodiumEthylenediamineDisuccinate, gluconolactone etc.

Example : Skin Lightening Roll-on Composition

[0037] The above subject matter is practiced in a body lotion composition as illustrated below in Table 3.

Table 3

Sensiva SC 50 1.5-3.0

4-butyl resorcinol (Kopsinol) 0.1-0.3

Perfume 0.25-0.4

DM Water q.s.

[0038] To make 1 ton of finished Roll-on product, required quantity of pasteurized demineralised water is charged to the main mixer. Phenoxyethanol followed by disodium EDTA are added and the stirring started. Then add polyol (glycerine) and mix well for 5 minutes. Heating is started to maintain approx. 75 deg C. Titanium dioxide and dryflo PC are slowly added and stirred well to avoid lump formation. Then viscous Sepiplus 400 is slowly added and stirred well to ensure uniform mixing. The recirculation is started and after 5 minutes of recirculation and ensuing homogeneity, the contents of the main mixer are cooled to below 40 deg C. Then a premix of BHT and perfume is added when the batch contents are below 40 deg C. Followed by this, a suspension of sumica pearl in demineralized water is added and continuously stirred to achieve uniform dispersion. Followed by this, niacinamide dissolved in demineralized water is added. Then, a low pH solution of glycolic acid is added to lower the pH of the composition. Having ensured the pH of the composition to be in the range of 4 to 5, dihydromyricetin (telocapil) is added. Sensive SC 50 is then added. 4-butyl resorcinol (Kopsinol) is dissolved in required quantities of 1,3- propane diol and after ensuring complete dissolution of kopsinol, this premix is added to the main mixer. The contents are mixed well and then recirculated for 5 minutes to ensure homogeneity of the bulk before discharging the batch for packing. The total duration of the batch time is 105 minutes. The colour, odour, appearance, pH and density of the finished good are checked.

Example u: Skin Lightening Body Mist and Gel Composition

[0039] In another example the subject matter is practiced in a body mist and gel composition as illustrated below in Table 4.

Table 4

1,3- Propane diol 8-15.0 8-15.0

4-butyl resorcinol (Kopsinol) 0.1-0.3 0.1-0.3

CarbopolUltrez 30 (Cross-linked - 0.8-1.5

acrylic acid polymer)

Xanthan gum / Guar gum - 0.2-0.3

Perfume 0.25-0.4 0.25-0.4

DM Water q.s. q.s.

[00 0] To make 1 ton of finished Body Mist product, required quantity of pasteurized demineralised water is charged to the main mixer and stirring done at 30 rpm for some time until the temperature is brought below 40 deg C. Then sufficient quantity of 1,3- propane diol, glycerine, and phenoxyethanol are added and the stirring continued. Then a premix of BHT and perfume is added. Followed by this, niacinamide and glycolic acid are added. Having ensured the pH is in the range of 4 to 5, thendihydromyricetin (telocapil™), and 4-butyl resorcinol (Kopsinol™) are added to the main mixer. In a completely aqueous composition, use of sufficient quantity of 1,3- propane diol helps to completely solubilize 4-butyl resorcinol. Otherwise, over a period of time, 4-butyl resorcinol would fall out of the solution and the particles would stick to the sides of the container and the dispensing mouth. The contents are mixed well and then recirculated for 5 minutes to ensure homogeneity of the bulk before discharging the batch for packing. The total duration of the batch time is approx. 35 minutes. The colour, odour, appearance, pH, and density of the finished good are checked.

[00 1] When making the aqueous gel, carbopolUltraz 30 with or without xanthan gum are slowly added to the main mixer after adding all the ingredients as described above to make a viscous aqueous gel. Care is taken to avoid lumps whenever powder material is added by stirring well. The thickener indicated in this example is one of its types and it is not limited to CarbopolUltraz 30 or natural gums like xanthan gum or guar gum. The thickeners include acacia gum, carrageenan, mineral thickeners (aluminium magnesium silicate, silica), cellulosic thickeners (hydroxyl ethyl cellulose), polyvinyl pyrolidone (PVP), guar hydroxypropyltrimonium chloride etc.

Example ς: Inhibition of Melanin Pigmentation on B16F10 Melanoma Cells

[00 2] For the purpose of testing effect of the cosmetic composition of the present subject matter on melanin production in cells, a number of experiments are performed.

[00 3] The efficacy of individual actives and their combinations in inhibiting melanin pigmentation in B16F10 mouse melanoma cells isstudied. Melanin is the skin pigment that determines the tone/colour of skin. B16F10 cells were cultured using Dulbecco's Modified Eagles Medium (DMEM media, Cat#i28oo-oi7, ThermoFisher Scientific). DMEM medium was supplemented with 10% Fetal Bovine Serum (Cat#i0270- 106, ThermoFisher Scientific). The actives herein refer to Telocapil™, Niacinamide, and Kopsinol™.

[00 ] Telocapil™, Niacinamide, and Kopsinol™ are assessed for their melanin inhibition capability. It shall become clear to a person in the art that effect of the composition on the melanin pigmentation must study in an environment such that the cells understudy survives during the experiment. If the cells fail to survive during the experiment, to draw a conclusion regarding effect of the composition on the melanin inhibition is not possible. Therefore the cells under experiment must be protected as best possible from the cytotoxic effects of the composition. To ensure the same, the experiments are conducted in concentrations that are suitable for observing the effect of the composition on the cells.

[00 5] The effect of actives on melanin inhibition is assessed individually as well as in combinations. The ratio of individual actives is maintained uniform in the combination study. The ratio of the actives maintained is Telocapil 1% : Niacinamide 1%) : Kopsinol 0.2%. The cells are exposed to actives for 48 hrs and the melanin content is spectrophotometrically quantified. Cytotoxicity of the actives and their combinations are concurrently determined. The cells are treated with IBMX (3-lsobutyl-i-methylxanthine) (ιοομΜ) and Νίθαηθητ^θ^οομΜ) as positive control & negative control respectively to check the validity of the experiments. [00 6] Following protocol is followed to study effect of actives on melanin inhibition. First, Melanocytes (B16F10) are seeded in 6-well cell culture plates in appropriate medium at a density of 50,000 cells/well. A day later, the cells are treated with appropriate actives and combinations. Second, the medium is removed from plate after 8hrs incubation and each well is washed twice with Phosphate-buffered saline (PBS). Third, about 0.5 ml of 2% TritonX-ioo is added to the well and cells are scrapped from the wells. TritonX-ioo causes lysis of the cells. The resulted cell lysates are transferred to 2ml tube and incubated for 1 hour on ice. Pellet is collected by centrifuging the tubes at 10,000 rpm/ °C for lomins. Fourth, Pellet is washed with 0.5 ml of ethanol: ether (1:1). The tubes having pellet are centrifuged at 10,000 rpm/4°C for lomins.The supernatant is removed. Fifth, about 0.5 ml NaOH/DMSO solution (0.2N NaOH and 2% DMSO) is added to the pellet and the tubes are incubated at 8o°C for smins to dissolve the insoluble pellet containing melanin. Sixth, the content of melanin is measured by observing absorbance at 45onm. Results are plotted to determine the unknown melanin content synthesized from different treatments. The results obtained are given shown in FIG. 1 and Table 5.

[00 7] From FIG. 1 and Table 5, it is evident that the cells treated with

Telocapil and Niacinamide in combination resulted in less melanin synthesis when compared to treatment with Telocapil alone. A further decrease in melanin synthesis was observed when cells were treated with a combination of Telocapil, Niacinamide and Kopsinol. Legends of the Table 5 are as follows, T: Telocapil, N: Niacinamide, K: Kopcinol, UT: Untreated.

Table 5

Example 6: Tyrosinase Inhibition Activity

[00 8] The melanin reduction may result from a number of reasons. One of the reasons for melanin reduction is inhibition of tyrosinase activity. Tyrosinase inhibition has been observed in experimental results of the present subject matter. Below discussion dwells into details of the experiment and results obtained thereof. It shall become clear to a person, after reading this specification, that experiments assessing other causes of melanin reduction may be performed, however for the sake of brevity only inhibition of tyrosinase activity is being discussed herein.

[00 9] Tyrosinase is a multicopper monoxygenase enzyme and is known as the polyphenoloxydase (PPO). It is involved in biosynthesis of melanin through oxidation of DOPA (dihydroxyphenylalanine) to dopaquinone (o-quinone), the latter then transforms into the melanin pigments through a series of enzymatic and non-enzymatic reactions in the skin. Inhibiting the activity of tyrosinase would result in reduction of melanin.

[0050] The in vitro tyrosinase inhibitory activity is determined by the dopachrome method. The actives are added individually and in combination at a concentration of 50 μg/ml to L-DOPA solution (10 mlW, dissolved in a 5 mM acetate buffer, pH 5). Subsequently, tyrosinase enzyme is added to each solution in different test tubes to a final concentration of 4 U/ml. The amount of dopachrome in the reaction mixture is measured after incubation at 38°C for 60 min at 475 nm by UV-Vis spectrophotometer. Kojic acid at the concentration of 50 μg/ml is used as reference and a blank reaction is conducted without a sample. All measurements are performed in triplicate sample. The inhibition activity of each active is expressed using the formula:

Percentage of Inhibitory Activity (IA%)= [(OD blank - ODwith active)/ OD blank] x ioo(OD means Optical Density)

Percentage Inhibition of Tyrosinase Activity

Table 6

[0051] From the above Table 6 Telocapil shows better tyrosinase inhibitory action than the reference ingredient (Kojic acid). However combination of Telocapil, Kopsinol and niacinamide shows better efficacy in this tyrosinase inhibition assay as compared to telocapil alone as well as reference Kojic acid.

Example 7: Discoloration of the composition:

[0052] The discoloration of the composition according to the present subject matter, having a pH modifier and without the pH modifier is studied. The compositions are observed for 12 weeks at temperature zero degree Celsius and forty five degree Celsius. At both the temperatures the composition without the pH modifier shows discoloration, whereas the composition of the present subject matter does not show any discoloration. FIG. 2 shows discoloration of the composition without pH modifier. FIG. 3 shows no discoloration of the composition according to the present subject matter. Therefore the present subject matter provides a composition which more stable and has longer shelf life.

[0053] While the subject matter described herein may be susceptible to various modifications and alternative forms. Specific embodiments have been discussed and described herein are only by way of examples. Alternate embodiments or modifications may be practiced without departing from the spirit of the subject matter. In some cases, some features may be emphasized while others are not. Further, the methods disclosed herein may be performed in manner and/or order in which the methods are explained. Alternatively, the methods may be performed in manner or order different than what is explained without departing from the spirit of the present subject matter. It should be understood that the subject matter is not intended to be limited to the particular forms disclosed. Rather, the subject matter is to cover all modifications, equivalents, and alternatives falling within the spirit and scope of the subject matter as described above.

[005 ] While describing the present subject matter, some proprietary terms and generally traded names have been used. These terms and names may include some expressions that may be trademarks or copyrighted subject matter. The applicant acknowledges the ownership of the respective proprietary subject matter and states that use of such tradenames or proprietary terms are solely for the purpose of ease of explanation and not for any malicious intent.

Claims

What is claimed is:

1. A cosmetic skin care composition comprising: dihydromyricetin, niacinamide,and a pH modifier on a cosmetically acceptable vehicle, wherein the pH modifier is configured to adjust pH of the cosmetic composition at a levelto control discoloration of the dihydromyricetin and chemical degradation of the niacinamide.

2. The composition of claim l, wherein the cosmetic composition is provided with the pH modifier in a concentration low enough to prevent discoloration of the dihydromyricetin and high enough to prevent chemical degradation of the niacinamide.

3. The composition of claim 1, wherein the pH modifier is present in any amount selected from: 0.1-20 wt%, 0.2-12.0 wt% and 0.5-8 wt%. it. The composition of claim 1, wherein the pH modifier is an alpha hydroxy acid.

5. The composition of claim 1, wherein the pH modifier is glycolic acid.

6. The composition of claim 1, wherein the composition has a pH value in any one of the range of: 3.0-6.0, 4.0-5.5 and 4.0- 5.0.

7. The composition of claim 1, wherein the dihydromyricetin is present in any amount selected from: 0.01-20 wt%, 0.1-5.0 wt% and 0.2-3.0 wt%.

8. The composition of claim 1, wherein the niacinamide is present in any amount selected from: 0.1-10 wt%, 0.2-5 wt% and 0.5-3 wt%. 9. The composition of claim 1, wherein the cosmetic composition further comprises resorcinol.

10. The composition of claim 9, wherein the resorcinol is 4-butyl resorcinol.

11. The composition of claim 9, wherein the resorcinol is present in any amount selected from: 0.1- 10 wt%, 0.1- 5 wt% and 0.2-0.5 wt%. 12. The composition of claim 1, wherein the composition also comprises a polyol selected from 1,3-propane diol, propylene glycol, glycerol, sorbitol, and polyethylene glycol.

13. The composition of claim 12, wherein the polyol is present in any amount selected from: 0.1- 30 wt%, 0.2- 20 wt%and 0.5- 16 wt%.

14. The composition of claim 1, wherein the composition further comprises an agent selected from a chelating agent and anantioxidantor a combination thereof.

15. The composition of claim 14, wherein the chelating agent is selected from disodium ethylenediaminetetraacetate (EDTA), diethylenetriaminepentaacetic acid (DTPA), trisodium ethylenediaminedisuccinate (EDDS) or a combination thereof.

16. The composition of claim 14, wherein the antioxidantis selected from sodium-bisulphite, butylated hydroxytoluene (BHT), ascorbic acid and its derivatives, tocopherol and its derivatives or a combination thereof.