FIELD OF THE INVENTION
The present invention relates to a novel, synergistically effective composition for topical application comprising alpha arbutin, Sohakuhi extract and process of preparing the same. More particularly, the invention pertains to a composition for topical application comprising alpha arbutin, Sohakuhi extract, niacinamide and 5 hyaluronic acid wherein the composition is effective in inhibiting tyrosinase activity in substantial manner.
BACKGROUND OF THE INVENTION
Skin whitening or skin lightening refers to the practice of using chemical substances in 10 an attempt to lighten skin tone or provide an even skin complexion by lessening the concentration of melanin. Several chemicals have been shown to be effective in skin whitening, while some have proven to be toxic or have questionable safety profiles, adding to the controversy surrounding their use and impacts on certain ethnic groups.
Certain humans at different phases of their lifetime, and in differing phases of their 15 health develop excess melanin and/or colored blemishes on the skin. This excess melanin can occur on any part of the human body, but most commonly appear on the face and back of the hands. These dark spots are caused by high levels of melanin in the keratinocytes located in the top layer of the epidermis.
Melanocytes are located deep in the stratum granulosum, produce melanin, and 20 through an unknown mechanism the melanin rises through about 100 cell layers to the surface where they exist as unsightly dark spots. Biochemically, Tyrosine amino acid (from diet) goes to Dopa; Dopa goes to Dopaquinone; Dopaquinone goes to Dopachrome; Dopachrome goes to Melanin. Melanin deposits are seen as the dark spots on the surface of the human skin. 25
Most skin-lightening treatments, which can reduce or block some amount of melanin production, are aimed at inhibiting tyrosinase. Many treatments use a combination of topical lotions or gels containing melanin-inhibiting ingredients along with a
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sunscreen, and a prescription retinoid. Depending on how the skin responds to these treatments, exfoliants either in the form of topical cosmetic or chemical peels — and lasers may be used.
There are various mechanisms described for achieving this. Inhibiting tyrosinase activity reduces the synthesis of melanin so that as existing skin cells are naturally 5 exfoliated keratinocytes with less melanin are eventually brought to the surface, giving the skin a lighter, more even toned complexion.
Tyrosinase is an oxidase that is the rate-limiting enzyme for controlling the production of melanin. It is mainly involved in two distinct reactions of melanin synthesis; firstly, the hydroxylation of a monophenol and secondly, the conversion of an o-diphenol to 10 the corresponding o-quinone. o-Quinone undergoes several reactions to eventually form melanin. Tyrosinase is a copper-containing enzyme present in plant and animal tissues that catalyzes the production of melanin and other pigments from tyrosine by oxidation, as in the blackening of a peeled or sliced potato exposed to air. It is found inside melanosomes which are synthesised in the skin melanocytes. In humans, the 15 tyrosinase enzyme is encoded by the TYR gene.
Tyrosinase carries out the oxidation of phenols such as tyrosine and dopamine using dioxygen (O2). In the presence of catechol, benzoquinone is formed. Hydrogens removed from catechol combine with oxygen to form water.
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Catechol-Quinone
The substrate specificity becomes dramatically restricted in mammalian tyrosinase which uses only L-form of tyrosine or DOPA as substrates, and has restricted requirement for L-DOPA as cofactor.
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Tyrosinase is the enzyme which catalyzes the amino acid tyrosine into dopa (dihydroxyphenylamine), as well as the change from dopa into dopaquinone. Skin lightening products are designed to inhibit the action of tyrosinase.
Hydroquinone is the most common inhibitor of the enzyme tyrosinase. However, hydroquinone is an irritant to some individuals, particularly those with light skin 5 types, and may be cytotoxic to melanocytes.
Although there are available in the state of the art various methods to achieve skin lightening is still a concern.
Hence, there is a need for a composition which is safe yet effective in results.
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OBJECT OF THE INVENTION
Accordingly, the main object of the invention is to provide a synergistically effective composition for topical application comprising alpha arbutin, mulberry extract for skin lightening.
Yet another object of the invention is to provide a composition for topical application 15 comprising alpha arbutin, mulberry extract, niacinamide and hyaluronic acid wherein the composition is effective in inhibiting tyrosinase activity in substantial manner.
Yet another object of the invention is to provide a process for preparing a composition for topical application comprising alpha arbutin, mulberry extract, niacinamide and hyaluronic acid wherein the composition is effective in inhibiting tyrosinase activity 20 in substantial manner.
Yet another object of the invention is to provide a composition for topical application with no side-effects.
Still another object of the invention is to provide a process of preparing such composition for topical application comprising alpha arbutin, mulberry extract, 25 niacinamide and hyaluronic acid.
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SUMMARY OF THE INVENTION
The present invention relates to a novel, synergistically effective composition for topical application comprising alpha arbutin, Sohakuhi extract and a process of preparing the same. More particularly, the invention pertains to a composition for topical application comprising alpha arbutin, Sohakuhi extract, niacinamide and 5 hyaluronic acid wherein the composition is effective in inhibiting tyrosinase activity in substantial manner.
In an embodiment of the present invention, alpha arbutin and Sohakuhi extract have a synergistic effect which is enhanced by Niacinamide or Vitamin PP. In addition, Vitamin PP has a collateral activity compared with alpha arbutin and Sohakuhi 10 extract. While these active ingredients inhibit tyrosinase and thus synthesis of melanin, Vitamin PP blocks the melanin transfer from melanosoma to the upper layer of the skin. Hyaluronic acid provides additional hydration to skin. The cumulative effect results into skin lightening, skin illumination, even-toning of all skin types, dark spot reduction, reduced tanning and enhanced moisturizing of skin. 15
The composition leads to a significant improvement in skin texture appearance over the application of skincare formulations containing this complex. The appearance shifted towards the finer, anisotropic features characteristic of illuminated skin while the appearance of hyper pigmentation was significantly improved. 20
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT
The present invention will now be described more fully hereinafter with reference to the accompanying drawings in which a preferred embodiment of the invention is 25 shown. This invention may, however, be embodied in many different forms and should not be construed as being limited to the embodiment set forth herein. Rather, the embodiment is provided so that this disclosure will be thorough, and will fully convey the scope of the invention to those skilled in the art.
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The present invention provides a novel, synergistically effective composition for topical application comprising alpha arbutin, Sohakuhi extract and a process of preparing the same. More particularly, the invention pertains to a composition for topical application comprising alpha arbutin, Sohakuhi extract, niacinamide and hyaluronic acid wherein the composition is effective in inhibiting tyrosinase activity 5 in substantial manner.
Alpha Arbutin is a functional skin lightening agent. Its efficacy has been proven in vitro assays and in vivo studies. The primary mechanism of action of Alpha arbutin is tyrosinase inhibition. Sohakuhi (or generally known as mulberry) extract has plant 10 derived functional ingredients having an anti-tyrosinase efficacy as well as antioxidant and stabilizing effect. Niacinamide (Vitamin PP) has a multi-step mechanism of action where it inhibits the transfer of melanosome from melanocites to keratinocites; helps prevent UV-induced deleterious molecular events; and helps stimulate collagen synthesis. Hyaluronic acid is a glycosaminoglycan component. It is a natural 15 moisturizer with excellent water binding capabilities. Upon application to the skin it forms a viscoelastic film in a manner similar to the way it holds water in the intercellular matrix of dermal connective tissues. Ideal moisturizer base improves the delivery of the other functional active ingredients belonging to the composition.
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The composition is prepared by a process comprising the following steps of:
a. Heating distilled water at 75°C;
b. Dissolving alpha Arbutin, Niacinamide and Hyluronic acid in distilled water at 75°C under stirring;
c. Cooling down the solution obtained in step b. to 30°C; 25
d. Adding Sohakuhi extract to the solution of step c. and mixing well; and
e. Cooling down the solution to room temperature to obtain the composition.
The preparation comprises a pool of active ingredients with an extraordinary breath of cutaneous benefits. The composition exerts multiple benefits on the appearance of 30 ageing and photo-damaged skin via multiple mechanisms, more and faster effect in attenuating the melanin production cascade. As skin pigmentation involves many
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genes at various steps and the production cascade of melanin into the skin is composed of several steps (each of them with a specific function) the composition of the present invention has been developed as a skin whitening agent and clarifying complex wherein the synergism indicated by the composition produces result surpassing the cumulative effect of the active ingredients. 5
The composition for the treatment or prevention of topical disorders of skin including skin darkening, acne spots, pigmentation, uneven skin tones, lack of hydration. The composition preferably comprising
(I) about 0.005 to 3% of Niacinamide; 10
(II) about 0.001 to 0.1% of Alpha Arbutin;
(III) about 0.000055 to 1% of Mulberry Extract; and
(IV) about 0.01 to 0.02% of Hyaluronic Acid.
The composition may further comprises skin conditioning agents, humectants, anti-15 oxidants and UV light absorbers in varying supportive percentage ranges suitably mixed to the weight of the composition.
In another embodiment, the synergistic advantage of the developed composition is observed in the presence of UV inhibitors or absorbers. Skin whitening benefits are 20 synergistically enhanced by combining at least one of the following; a tyrosinase inhibiting or competing ingredient, a melanin correcting ingredients and suitable anti-oxidants and humectants. The additional inclusion of a UV inhibitor/absorber enhances the properties of the whitening composition and supports the function of the ingredient complex in fighting tyrosinase activity and excess melanin production. 25
Human assessment trial was conducted for 4 weeks with following compositions:
Composition 1: preferably comprising (I) about 0.002% to about 1.5% of Niacinamide, (II) about 0.0005% to about 0.05% of Alpha Arbutin, (III) about 30 0.000027% to about 0.5% of Mulberry Extract, (IV) about 0.005% to about 0.01% of Hyaluronic Acid.
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The activity of the composition was assessed on human subjects that did not provide satisfactory whitening results except skin hydrating efficacy in this concentration range. The composition was further developed to obtain a result-oriented composition.
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Composition 2: preferably comprising (I) about 0.0037% to about 2.25% of Niacinamide, (II) about 0.0007% to about 0.075% of Alpha Arbutin, (III) about 0.00004% to about 0.75% of Mulberry Extract, (IV) about 0.007% to about 0.015% of Hyaluronic Acid.
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Upon study, it is observed that the composition provides satisfactory results when the ingredients were used in high concentration range.
Composition 3: preferably comprising (I) about 0.005% to about 3% of Niacinamide, (II) about 0.001% to about 0.1% of Alpha Arbutin, (III) about 0.000055% to about 1% 15 of Mulberry Extract, (IV) about 0.01% to about 0.02% of Hyaluronic Acid.
A significant improvement in skin texture and appearance was observed. The human assessment trial was satisfactory to the extent that there was a visible lightening of uneven skin tone and dark spots. Further, overall freshness, brightness and radiance 20 properties were experienced by the human subjects. It is noted that the presence of Hyaluronic acid enhances the moisture retaining capacity of the composition. The composition also found satisfactory in synergistically improving skin lightening effect along with UV absorbing capacity.
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Mulberry Extract is a multifunctional skin-lightening active ingredient. The efficacy of Mulberry Extract as an inhibitor of tyrosinase has been demonstrated in vitro. The formation of dopachrome, an intermediate production of melanogenesis, was determined. The inhibition curve shows that UVA URSI extract inhibits melanogenesis at low concentrations and can therefore be considered as a very 30 effective tyrosinase inhibitor.
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The combination of the four selected ingredients provides synergistic results. Vitamin PP or Niacinamide has also a collateral activity compared with α-arbutin and mulberry extract. These active ingredients inhibit tyrosinase and the synthesis of melanin. Vitamin PP blocks the melanin transfer from melanosoma to the upper layer of the skin. This formula contains up to 0.02% of hyaluronic acid along with UV 5 absorbers.
Composition 4: preferably comprising (I) about 0.0062% to about 3.75% of Niacinamide, (II) about 0.0012% to about 0.12% of Alpha Arbutin, (III) about 0.00007% to about 1.25% of Mulberry Extract, (IV) about 0.012% to about 0.025% of 10 Hyaluronic Acid.
The human assessment trial was satisfactory to the extent that visible whitening results were experienced along with reduction in dark spots and uneven skin tone. However, subjects reported heaviness in texture on application and experienced 15 discomfort during the trial period. The formulation was further adjusted with change in concentrations of skin conditioners and humectants. However, the subjects were not satisfied with the texture of the composition.
Composition 5: preferably comprising (I) about 0.0075% to about 4.5% of 20 Niacinamide, (II) about 0.0015% to about 0.15% of Alpha Arbutin, (III) about 0.000082% to about 1.5% of Mulberry Extract, (IV) about 0.015% to about 0.03% of Hyaluronic Acid.
When ingredients are used in high concentration range, it is observed that the 25 composition possesses stability and hypersensitivity issues as subjects experienced irritation and discomfort upon application. Hence, the high concentration of the ingredients was not recommended for topical formulations.

CLAIMS
We claim:
1. A synergistic cosmetic or pharmaceutical formulation for topical application for skin lightening or whitening, or brightening comprising of
(I) Niacinamide, 0.005% to 3%, for inhibiting the transfer of melanosome 5 from melanocytes to keratinocytes thereby reducing human skin pigmentation and facial spots;
(II) Alpha Arbutin, 0.001% to 0.1%, for acting as tyrosinase inhibitior thereby acting as skin lightening agent;
(III) Mulberry Extract, 0.000055% to 1%, for acting as an anti-tyrosinase, 10 antioxidant and the formulation stabilizer; and
(IV) Hyaluronic Acid, 0.01% to 0.02%, for acting as a natural moisturizer having excellent water binding capabilities improving the delivery of the other functional active ingredients by acting as a viscoelastic film on the skin; 15
wherein the formulation is effective in inhibiting tyrosinase activity in substantial manner.
2. The formulation according to claim 1 wherein the formulation further comprises a cosmetically acceptable delivery system including water and oil emulsions, suspensions, colloids, or anhydrous systems. 20
3. The formulation according to claim 2 wherein the cosmetically acceptable delivery system is selected from a lotion, cream, shampoo, shower gel, cleanser, bath oil, salve, paste, lip balm, serum, gel, body splash, cologne, and other such as well known topical cosmetic and pharmaceutical delivery systems.
4. A method of preparing a synergistic cosmetic or pharmaceutical formulation for 25 topical application for skin lightening or whitening, or brightening comprising the steps of:
a) heating distilled water to 75°C;
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b) dissolving alpha Arbutin, Niacinamide and Hyluronic acid in distilled water at 75°C under constant stirring to create a solution;
c) allowing the solution to cool down to 30°C;
d) adding Mulberry extract to the cooled solution and mixing well to create a formulation; and 5
e) cooling down the solution to room temperature to obtain the formulation.
5. The method according to claim 4 wherein the method further comprises adding a cosmetically acceptable delivery system like water and oil emulsions, suspensions, colloids, or anhydrous systems.
6. The method according to claim 5 wherein the cosmetically acceptable delivery 10 system is selected from a lotion, cream, shampoo, shower gel, cleanser, bath oil, salve, paste, lip balm, serum, gel, body splash, cologne, and other such as well known topical cosmetic and pharmaceutical delivery systems.