TECHNICAL FIELD
[001] The subject matter described herein in general relates to the field of cosmetic compositions, and in particular relates to cosmetic compositions to prevent or ameliorate the effects of aging on skin.
BACKGROUND OF INVENTION
[002] Autophagy is a major lysosome-dependent catabolic pathway, is required to generate nutrients and energy during starvation and to perform homeostatic functions such as clearance of toxic misfolded proteins or damaged organelles. Dysfunctional autophagy has been found in many lysosomal storage disorders as well as in other major disease groups, such as neurodegenerative diseases, malignancy, inflammatory diseases and aging. Skin aging is natural process associated with a number of pathophysiology's that can reduce quality of life and longevity. Physiologically, skin aging results from dysregulation of key regulatory proteins (i.e., protein signatures) which in turn, interact and interfere with the intracellular pathways, thereby leading to physiological aging of tissues, cells and subcellular components.
[003] Conventionally, medical procedures, such as dermal injections and reconstructive surgery, are available to reduce the signs of aging. Cosmetic surgery has recently grown in popularity to aesthetically enhance the appearance of skin and even the appearance of the skin of the vulva and labia. These procedures, however, are not always desirable options as surgery can be costly, painful and very invasive. US9138400 discusses the use of various compounds to increase autophagy within skin cells through the up-regulation of the ATG5-12 and MAP-LC3 protein complexes.
[004] US5650137 discloses a composition comprising synergistically effective amounts of at least one superoxide dismutase (SOD) and at least one porphyrin selected from the group consisting of chlorophyll A, chlorophyllin and haemoglobin, to combat skin aging. US9333169 discloses the use of Candida saitoana or an active ingredient that is obtained from Candida saitoana as a cosmetic active ingredient, in particular for the detoxification of skin cells.

[005] US8512764 discloses the use of a cosmetic composition comprising an effective amount of at least one cutaneous cell autophagy activator as a cosmetic active ingredient for detoxifying skin and/or for preventing or combating cutaneous aging. WO2017102738 discloses a composition that can mitigate aging and to maintain health by administering a composition comprising at least one protein-homeostasis-influencing saccharide-based substance, an anti-amyloidogenic substance, a Krebs cycle metabolite, glycine, gingko biloba, low dose lithium, a prebiotic, or combinations thereof, enabling a synergistic and enhancing effect on the aging process.
[006] US8084062 discloses an anti-aging cosmetic composition containing Hibiscus esculentus extracts and at least one selected from the group consisting of oleanolic acid, ursolic acid, glycyrhetinic acid and retinol, showing high safety to skin and wrinkle-improvement effect. US11078030 discloses a topical composition comprising crape myrtle extract in an amount effective to improve the aesthetic appearance of skin. Although several such compositions are available in the market as of today, there still exists a need to develop a cosmetic composition which can prevent or ameliorate the effects of aging on skin.
SUMMARY OF THE INVENTION
[007] In an aspect of the present invention, there is provided a composition
comprising: a) dihydroxyresveratrol; and b) pepstatin A, wherein
dihydroxyresveratrol, and pepstatin A w/w ratio is in a range of 8:1 to 12:1.
[008] In another aspect of the present invention, there is provided a process for
preparing the composition comprising: a) dihydroxyresveratrol; and b) pepstatin A,
wherein dihydroxyresveratrol, and pepstatin A w/w ratio is in a range of 8:1 to 12:1;
said process comprising the steps of: a) obtaining dihydroxyresveratrol; b) obtaining
pepstatin A; and c) contacting dihydroxyresveratrol and pepstatin A to obtain the
composition.
[009] These and other features, aspects, and advantages of the present subject
matter will be better understood with reference to the following description and
appended claims. This summary is provided to introduce a selection of concepts in a

simplified form. This summary is not intended to identify key features or essential features of the claimed subject matter, nor is it intended to be used to limit the scope of the claimed subject matter.
BRIEF DESCRIPTION OF THE DRAWINGS
[0010] The detailed description is described with reference to the accompanying
figures. The same numbers are used throughout the drawings to reference like
features and components.
[0011] Figure 1 depicts a schematic illustration of the process flow carried out in
proteomic analysis, in accordance with an implementation of the present subject
matter.
[0012] Figure 2 depicts a graph showing number of proteins identified using
Orbitrap MS/proteome discoverer in control, individual and combinatorial
treatments in treated B16 cells, in accordance with an implementation of the present
subject matter.
[0013] Figure 3 is a graph depicting the effect of a composition comprising
dihydroxyresveratrol and pepstatin A, on sequestome 1 protein levels
[0014] Figure 4 is a graph depicting the effect of a composition comprising
dihydroxyresveratrol and pepstatin A, on Mn-superoxide dismutase (MnSOD)
protein levels, in accordance with an implementation of the present subject matter.
[0015] Figure 5 is a graph depicting the effect of a composition comprising
dihydroxyresveratrol and pepstatin A, on lysosome-associated membrane
glycoprotein 2 protein levels (LAMP), in accordance with an implementation of the
present subject matter.
[0016] Figure 6 is a graph depicting the effect of a composition comprising
dihydroxyresveratrol and pepstatin A, on lysosomal alpha glucosidase (GAA)
protein levels, in accordance with an implementation of the present subject matter.
[0017] Figure 7 is a graph depicting the effect of a composition comprising
dihydroxyresveratrol and pepstatin A, on chymotrypsinogen levels protein levels, in
accordance with an implementation of the present subject matter.

[0018] Figure 8 is a graph depicting the effect of a composition comprising dihydroxyresveratrol and pepstatin A, on ubiquitin carboxyterminal hydrolase (USCHL1) protein levels, in accordance with an implementation of the present subject matter.
DETAILED DESCRIPTION OF THE INVENTION
[0019] Those skilled in the art will be aware that the present disclosure is subject to
variations and modifications other than those specifically described. It is to be
understood that the present disclosure includes all such variations and modifications.
The disclosure also includes all such steps, features, compositions, and compounds
referred to or indicated in this specification, individually or collectively, and any and
all combinations of any or more of such steps or features.
Definitions
[0020] For convenience, before further description of the present disclosure, certain
terms employed in the specification, and examples are delineated here. These
definitions should be read in the light of the remainder of the disclosure and
understood as by a person of skill in the art. The terms used herein have the meanings
recognized and known to those of skill in the art, however, for convenience and
completeness, particular terms and their meanings are set forth below.
[0021] The articles "a", "an" and "the" are used to refer to one or to more than one
(i.e., to at least one) of the grammatical object of the article.
[0022] The terms "comprise" and "comprising" are used in the inclusive, open sense,
meaning that additional elements may be included. It is not intended to be construed
as "consists of only".
[0023] Throughout this specification, unless the context requires otherwise the word
"comprise", and variations such as "comprises" and "comprising", will be
understood to imply the inclusion of a stated element or step or group of element or
steps but not the exclusion of any other element or step or group of element or steps.
[0024] The term "including" is used to mean "including but not limited to".
"Including" and "including but not limited to" are used interchangeably.

[0025] Ratios, concentrations, amounts, and other numerical data may be presented herein in a range format. It is to be understood that such range format is used merely for convenience and brevity and should be interpreted flexibly to include not only the numerical values explicitly recited as the limits of the range, but also to include all the individual numerical values or sub-ranges encompassed within that range as if each numerical value and sub-range is explicitly recited. For example, a range of 8:1 to 12:1, should be construed as including sub-ranges of 9:1 to 11:1, 8.1:1 to 11.9:1, and so on.
[0026] The term "at least one" is used to mean one or more and thus includes individual components as well as mixtures/combinations.
[0027] For the purposes of the present disclosure, the terms "diluents", "preservatives", "viscosity modifiers", "bulking agents", "chelating agents", "stabilizing agents", "humectants", "surfactants", "pH modifiers", "perfume", "texture enhancer", "emollients", "skin conditioning agents", and "antioxidants", refer to the generally known components used in the art. The specific components of the above-described categories have been mentioned in the present disclosure wherever applicable. Wherever not mentioned, it can be construed that any component falling under the categories can be used as part of the composition. [0028] Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this disclosure belongs. Although any methods and materials similar or equivalent to those described herein can be used in the practice or testing of the disclosure, the preferred methods, and materials are now described. All publications mentioned herein are incorporated herein by reference.
[0029] The present disclosure is not to be limited in scope by the specific embodiments described herein, which are intended for the purposes of exemplification only. Functionally-equivalent products, compositions, and methods are clearly within the scope of the disclosure, as described herein. [0030] Conventionally used cosmetic products and medical procedures described above are suitable for treating aged skin, alternative compositions for improving skin are desirable. Accordingly, there exists a need to develop alternative compositions

for improving the appearance of aging skin. It would be highly advantageous if the compositions and methods could be topically applied such that invasive, painful, and costly medical procedures could be avoided.
[0031] The present disclosure provides a novel composition comprising dihydroxyresveratrol and pepstatin A for the modulation of autophagy in aging and related conditions. For this purpose, a high-throughput proteomic based-mass analysis was used to identify autophagy-related proteins. Based on the results of these studies, biological and cosmeceutical agents useful in the modulation of these proteins and their products were identified and a composition for the modulation of autophagy which enhances cell detoxification system were identified. [0032] Dihydroxyresveratrol also known as 2, 1v* 2* 3v-tetrahydroxystilbene, a new derivative of oxyresveratrol is having actives potent tyrosinase inhibition activity than oxyresveratrol. It has the molecular weight of 246.26. Dihydroxyresveratrol WjWdfWV fZW Z[YZWef fkdae[`Wve [`Z[T[f[a` WXXWUf* with an IC50 value of 0.3 ± 0.05 µM, approximately ~50-fold stronger than the reference control kojic acid (IC50 16.1± 1.4 µM) (Chaita E et. al., Molecules, 2017, 22(4), 514).
[0033] Pepstatin A is an inhibitor of acid proteases (aspartyl peptidases). It forms a 1:1 complex with proteases such as pepsin, renin, cathepsin D, bovine chymosin, and protease B. The inhibitor is highly selective and does not inhibit thiol proteases, neutral proteases, or serine proteases. Pepstatin A can be used in conjunction with E64-d and leupeptin A to inhibit the degradation of autophagic cargo inside autophagosomes. Recent studies show that pepstatin A alters the host cell autophagic machinery and leads to a decrease in influenza A virus production (Matarrese P et. al., 2011 & Tashiro K et. al., Biochem. Biophys. Res. Commun., 2014, Jan 3;443(1):167-72).
[0034] The present disclosure is directed towards a combination dihydroxyresveratrol and pepstatin A, which when used in defined w/w ratios could maintain or enhance skin health through regulation of important proteins related to skin physiology, through autophagy pathway, as observed in B16 mouse melanoma cells model.

[0035] In an embodiment of the present disclosure, there is provided a composition
comprising: a) dihydroxyresveratrol; and b) pepstatin A, wherein
dihydroxyresveratrol, and pepstatin A w/w ratio is in a range of 8:1 to 12:1. In
another embodiment, dihydroxyresveratrol, and pepstatin A w/w ratio is in a range
of 9:1 to 11:1.
[0036] In another embodiment, there is provided a composition as disclosed herein,
wherein dihydroxyresveratrol, and pepstatin A w/w ratio is 10:1.
[0037] In an embodiment of the present disclosure, there is provided a composition
comprising: a) dihydroxyresveratrol; and b) pepstatin A, wherein
dihydroxyresveratrol, and pepstatin A w/w ratio is 10:1.
[0038] In another embodiment of the present disclosure, there is provided a
composition as described herein, wherein dihydroxyresveratrol has weight
percentage in a range of 0.5 to 1.6% with respect to the composition. In another
embodiment, dihydroxyresveratrol has weight percentage in a range of 0.75 to 1.25%
with respect to the composition.
[0039] In another embodiment of the present disclosure, there is provided a
composition comprising: a) dihydroxyresveratrol; and b) pepstatin A, wherein
dihydroxyresveratrol, and pepstatin A w/w ratio is in the range of 8:1 to 12:1, and
whereindihydroxyresveratrol has weight percentage in a range of 0.5 to 1.6% with
respect to the composition.
[0040] In another embodiment of the present disclosure, there is provided a
composition as described herein, wherein pepstatin A has weight percentage in a
range of 0.05 s 0.2% with respect to the composition. In another embodiment,
pepstatin A has weight percentage in a range of 0.1 s 0.2% with respect to the
composition.
[0041] In another embodiment of the present disclosure, there is provided a
composition comprising: a) dihydroxyresveratrol; and b) pepstatin A, wherein
dihydroxyresveratrol, and pepstatin A w/w ratio is in the range of 8:1 to 12:1, and
wherein pepstatin A has weight percentage in a range of 0.05 s 0.2% with respect to
the composition.

[0042] In another embodiment of the present disclosure, there is provided a composition comprising: a) dihydroxyresveratrol; and b) pepstatin A, wherein dihydroxyresveratrol, and pepstatin A w/w ratio is in the range of 8:1 to 12:1, and wherein dihydroxyresveratrol has weight percentage in a range of 0.5 to 1.6% with respect to the composition, and wherein pepstatin A has weight percentage in a range of 0.05 s 0.2% with respect to the composition.
[0043] In an embodiment of the present disclosure, there is provided a composition as described herein, wherein the composition upregulates the expression of Mn-superoxide dismutase.
[0044] In another embodiment of the present disclosure, there is provided a composition comprising: a) dihydroxyresveratrol; and b) pepstatin A, wherein dihydroxyresveratrol, and pepstatin A w/w ratio is in the range of 8:1 to 12:1, and wherein the composition upregulates the expression of Mn-superoxide dismutase. [0045] In another embodiment of the present disclosure, there is provided a composition comprising: a) dihydroxyresveratrol; and b) pepstatin A, wherein dihydroxyresveratrol, and pepstatin A w/w ratio is in the range of 8:1 to 12:1, and wherein dihydroxyresveratrol has weight percentage in a range of 0.5 to 1.6% with respect to the composition, and wherein pepstatin A has weight percentage in a range of 0.05 s 0.2% with respect to the composition, and wherein the composition upregulates the expression of Mn-superoxide dismutase.
[0046] In an embodiment of the present disclosure, there is provided a composition as described herein, said composition upregulates the expression of sequestome-1 protein.
[0047] In another embodiment of the present disclosure, there is provided a composition comprising: a) dihydroxyresveratrol; and b) pepstatin A, wherein dihydroxyresveratrol, and pepstatin A w/w ratio is in the range of 8:1 to 12:1, and wherein the composition upregulates the expression of sequestome-1 protein. [0048] In another embodiment of the present disclosure, there is provided a composition comprising: a) dihydroxyresveratrol; and b) pepstatin A, wherein dihydroxyresveratrol, and pepstatin A w/w ratio is in the range of 8:1 to 12:1, and wherein dihydroxyresveratrol has weight percentage in a range of 0.5 to 1.6% with

respect to the composition, and wherein pepstatin A has weight percentage in a range of 0.05 s 0.2% with respect to the composition, and wherein the composition upregulates the expression the expression of sequestome-1 protein. [0049] In an embodiment of the present disclosure, there is provided a composition
+# as described herein, said composition upregulates the expression of lysosome-associated membrane glycoprotein 2.
[0050] In another embodiment of the present disclosure, there is provided a composition comprising: a) dihydroxyresveratrol; and b) pepstatin A, wherein dihydroxyresveratrol, and pepstatin A w/w ratio is in the range of 8:1 to 12:1, and
&# wherein the composition upregulates the expression of lysosome-associated membrane glycoprotein 2.
[0051] In another embodiment of the present disclosure, there is provided a composition comprising: a) dihydroxyresveratrol; and b) pepstatin A, wherein dihydroxyresveratrol, and pepstatin A w/w ratio is in the range of 8:1 to 12:1, and
+# wherein dihydroxyresveratrol has weight percentage in a range of 0.5 to 1.6% with respect to the composition, and wherein pepstatin A has weight percentage in a range of 0.05 s 0.2% with respect to the composition, and wherein the composition upregulates the expression lysosome-associated membrane glycoprotein 2. [0052] In an embodiment of the present disclosure, there is provided a composition
&# as described herein, said composition upregulates the expression of lysosomal alpha glucosidase.
[0053] In another embodiment of the present disclosure, there is provided a composition comprising: a) dihydroxyresveratrol; and b) pepstatin A, wherein dihydroxyresveratrol, and pepstatin A w/w ratio is in the range of 8:1 to 12:1, and
+# wherein the composition upregulates the expression of lysosomal alpha glucosidase. [0054] In another embodiment of the present disclosure, there is provided a composition comprising: a) dihydroxyresveratrol; and b) pepstatin A, wherein dihydroxyresveratrol, and pepstatin A w/w ratio is in the range of 8:1 to 12:1, and wherein dihydroxyresveratrol has weight percentage in a range of 0.5 to 1.6% with
&# respect to the composition, and wherein pepstatin A has weight percentage in a range

of 0.05 s 0.2% with respect to the composition, and wherein the composition
upregulates the expression of lysosomal alpha glucosidase.
[0055] In an embodiment of the present disclosure, there is provided a composition
as described herein, said composition upregulates the expression of
chymotrypsinogen B.
[0056] In another embodiment of the present disclosure, there is provided a
composition comprising: a) dihydroxyresveratrol; and b) pepstatin A, wherein
dihydroxyresveratrol, and pepstatin A w/w ratio is in the range of 8:1 to 12:1, and
wherein the composition upregulates the expression of chymotrypsinogen B.
[0057] In another embodiment of the present disclosure, there is provided a
composition comprising: a) dihydroxyresveratrol; and b) pepstatin A, wherein
dihydroxyresveratrol, and pepstatin A w/w ratio is in the range of 8:1 to 12:1, and
wherein dihydroxyresveratrol has weight percentage in a range of 0.5 to 1.6% with
respect to the composition, and wherein pepstatin A has weight percentage in a range
of 0.05 s 0.2% with respect to the composition, and wherein the composition
upregulates the expression of chymotrypsinogen B.
[0058] In an embodiment of the present disclosure, there is provided a composition
as described herein, said composition upregulates the expression of ubiquitin
carboxyterminal hydrolase.
[0059] In another embodiment of the present disclosure, there is provided a
composition comprising: a) dihydroxyresveratrol; and b) pepstatin A, wherein
dihydroxyresveratrol, and pepstatin A w/w ratio is in the range of 8:1 to 12:1, and
wherein the composition downregulates the expression of ubiquitin carboxyterminal
hydrolase.
[0060] In another embodiment of the present disclosure, there is provided a
composition comprising: a) dihydroxyresveratrol; and b) pepstatin A, wherein
dihydroxyresveratrol, and pepstatin A w/w ratio is in the range of 8:1 to 12:1, and
wherein dihydroxyresveratrol has weight percentage in a range of 0.5 to 1.6% with
respect to the composition, and wherein pepstatin A has weight percentage in a range
of 0.05 s 0.2% with respect to the composition, and wherein the composition
downregulates the expression of ubiquitin carboxyterminal hydrolase.

[0061] In an embodiment of the present disclosure there is provided a composition as described herein, wherein the composition further comprises at least one excipient selected from diluent, preservative, viscosity modifier, bulking agent, chelating agent, stabilizing agent, humectant, surfactant, pH modifier, perfume, texture enhancer, emollient, skin conditioning agent, antioxidant, and combinations thereof. In an embodiment of the present disclosure, the preservative is at least one selected from a group consisting of caprylyl glycol, glyceryl caprylate, phenylpropanol, phenoxythanol, ethylhexyl glycerin, and combinations thereof; the viscosity modifier is sodium polyacrylate; the emollient is at least one selected from a group consisting of glyceryl stearate citrate, glyceryl caprylate, isoamyl laurate, C12-15 alkyl benzoate, potassium cetyl phosphate (and) hydrogenated palm glycerides, cetostearyl alcohol, and combinations thereof; the antioxidant is tocopheryl acetate; the viscosity modifier is at least one selected from a group consisting of ammonium acryloyl s dimethyltaurate, VP copolymer, xanthum gum, the texture enhancer is acrylates/C10-30 alkyl acrylate cross polymer, hydroxyethyl acrylate / sodium acryloyldimethyl taurate copolymer (and) isohexadecane (and) polysorbate 60, and combinations thereof; the chelating agent is disodium ethylene disodium tetraacetic acid (EDTA); the bulking agent is magnesium sulfate; the pH modifier is triethanolamine, the surfactant is triethanolamine; the humectant is glycerol, the solvent is water, glycerol, and combinations thereof.
[0062] In another embodiment of the present disclosure, there is provided a composition comprising: a) dihydroxyresveratrol; and b) pepstatin A, wherein dihydroxyresveratrol, and pepstatin A w/w ratio is in the range of 8:1 to 12:1, and wherein the composition further comprises at least one excipient selected from diluents, preservatives, viscosity modifiers, bulking agents, chelating agents, stabilizing agents, humectants, surfactants, pH modifiers, perfume, texture enhancer, emollients, skin conditioning agents, antioxidants, and combinations thereof. [0063] In another embodiment of the present disclosure, there is provided a composition comprising: a) dihydroxyresveratrol; and b) pepstatin A, wherein dihydroxyresveratrol, and pepstatin A w/w ratio is in the range of 8:1 to 12:1, and wherein dihydroxyresveratrol has weight percentage in a range of 0.5 to 1.6% with

respect to the composition, and wherein pepstatin A has weight percentage in a range of 0.05 s 0.2% with respect to the composition, and wherein the composition further comprises at least one excipient selected from diluents, preservatives, viscosity modifiers, bulking agents, chelating agents, stabilizing agents, humectants, surfactants, pH modifiers, perfume, texture enhancer, emollients, skin conditioning agents, antioxidants, and combinations thereof.
[0064] In an embodiment of the present disclosure, there is provided a composition as described herein, wherein the composition comprises a) dihydroxyresveratrol having a concentration in a range of 8 s 12 µM; b) pepstatin A having a concentration in a range of 0.8 s 1.2 µM; and c) at least one diluent selected from the group consisting of water and glycerol. In another embodiment, the composition comprises a) dihydroxyresveratrol having a concentration in a range of 8.5 s 11.5 µM; b) pepstatin A having a concentration in a range of 0.9 s 1.1 µM; and c) at least one diluent selected from the group consisting of water and glycerol [0065] In another embodiment of the present disclosure, there is provided a composition comprising: a) dihydroxyresveratrol; and b) pepstatin A, wherein dihydroxyresveratrol, and pepstatin A w/w ratio is in the range of 8:1 to 12:1, and wherein the composition further comprises at least one excipient selected from diluents, preservatives, viscosity modifiers, bulking agents, chelating agents, stabilizing agents, humectants, surfactants, pH modifiers, perfume, texture enhancer, emollients, skin conditioning agents, antioxidants, and combinations thereof, and wherein the composition comprises a) dihydroxyresveratrol having a concentration in a range of 8 s 12 µM; b) pepstatin A having a concentration in a range of 0.8 s 1.2 µM; and c) at least one diluent selected from the group consisting of water and glycerol.
[0066] In another embodiment of the present disclosure, there is provided a composition comprising: a) dihydroxyresveratrol; and b) pepstatin A, wherein dihydroxyresveratrol, and pepstatin A w/w ratio is in the range of 8:1 to 12:1, and wherein dihydroxyresveratrol has weight percentage in a range of 0.5 to 1.6% with respect to the composition, and wherein pepstatin A has weight percentage in a range of 0.05 s 0.2% with respect to the composition, and wherein the composition

comprises a) dihydroxyresveratrol having a concentration in a range of 8 s 12 µM; b) pepstatin A having a concentration in a range of 0.8 s 1.2 µM; and c) at least one diluent selected from the group consisting of water and glycerol. [0067] In an embodiment, there is provided a process for preparing a composition comprising: a) dihydroxyresveratrol; and b) pepstatin A, wherein dihydroxyresveratrol, and pepstatin A w/w ratio is in the range of 8:1 to 12:1, said process comprising the steps of: a) obtaining dihydroxyresveratrol; b) obtaining pepstatin A; and c) contacting dihydroxyresveratrol and pepstatin A to obtain the composition.
[0068] In another embodiment of the present disclosure, there is provided a process for preparing a composition comprising: a) dihydroxyresveratrol; and b) pepstatin A, wherein dihydroxyresveratrol, and pepstatin A w/w ratio is in the range of 8:1 to 12:1, and wherein dihydroxyresveratrol has weight percentage in a range of 0.5 to 1.6% with respect to the composition, and wherein pepstatin A has weight percentage in a range of 0.05 s 0.2% with respect to the composition, and wherein said process comprising the steps of: a) obtaining dihydroxyresveratrol; b) obtaining pepstatin A; and c) contacting dihydroxyresveratrol and pepstatin A to obtain the composition. [0069] In another embodiment of the present disclosure, there is provided a process for preparing a composition comprising: a) dihydroxyresveratrol; and b) pepstatin A, wherein dihydroxyresveratrol, and pepstatin A w/w ratio is in the range of 8:1 to 12:1, and wherein the composition further comprises at least one excipient selected from diluents, preservatives, viscosity modifiers, bulking agents, chelating agents, stabilizing agents, humectants, surfactants, pH modifiers, perfume, texture enhancer, emollients, skin conditioning agents, antioxidants, and combinations thereof and wherein said process comprising the steps of: a) obtaining dihydroxyresveratrol; b) obtaining pepstatin A; c) obtaining the at least one excipient; and d) contacting dihydroxyresveratrol, pepstatin A, with the at least one excipient, to obtain the composition.
[0070] In another embodiment of the present disclosure, there is provided a process for preparing a composition comprising: a) dihydroxyresveratrol; and b) pepstatin A, wherein dihydroxyresveratrol, and pepstatin A w/w ratio is in the range of 8:1 to

12:1, and wherein dihydroxyresveratrol has weight percentage in a range of 0.5 to 1.6% with respect to the composition, and wherein pepstatin A has weight percentage in a range of 0.05 s 0.2% with respect to the composition, and wherein the composition further comprises at least one excipient selected from diluents, preservatives, viscosity modifiers, bulking agents, chelating agents, stabilizing agents, humectants, surfactants, pH modifiers, perfume, texture enhancer, emollients, skin conditioning agents, antioxidants, and combinations thereof and wherein said process comprising the steps of: a) obtaining dihydroxyresveratrol; b) obtaining pepstatin A; c) obtaining the at least one excipient; and d) contacting dihydroxyresveratrol, pepstatin A, with the at least one excipient, to obtain the composition.
[0071] In another embodiment of the present disclosure, there is provided a process for preparing a composition comprising: a) dihydroxyresveratrol; and b) pepstatin A, wherein dihydroxyresveratrol, and pepstatin A w/w ratio is in the range of 8:1 to 12:1, and wherein dihydroxyresveratrol has weight percentage in a range of 0.5 to 1.6% with respect to the composition, and wherein pepstatin A has weight percentage in a range of 0.05 s 0.2% with respect to the composition, and wherein the composition comprises a) dihydroxyresveratrol having a concentration in a range of 8 s 12 µM; b) pepstatin A having a concentration in a range of 0.8 s 1.2 µM; and c) at least one diluent selected from the group consisting of water and glycerol, and wherein the composition further comprises at least one excipient selected from diluents, preservatives, viscosity modifiers, bulking agents, chelating agents, stabilizing agents, humectants, surfactants, pH modifiers, perfume, texture enhancer, emollients, skin conditioning agents, antioxidants, and combinations thereof and wherein said process comprising the steps of: a) obtaining dihydroxyresveratrol; b) obtaining pepstatin A; c) obtaining the at least one excipient; and d) contacting dihydroxyresveratrol, pepstatin A, with the at least one excipient, to obtain the composition.
[0072] In an embodiment of the present disclosure, there is provided a composition as described herein, wherein the composition is effective in promoting skin autophagy process.

[0073] In another embodiment of the present disclosure, there is provided a composition comprising: a) dihydroxyresveratrol; and b) pepstatin A, wherein dihydroxyresveratrol, and pepstatin A w/w ratio is in the range of 8:1 to 12:1, and wherein the composition is effective in promoting skin autophagy process.
# [0074] In an embodiment of the present disclosure, the composition of the present
disclosure relates to cosmetic compositions comprising at least one activator of the
autophagy of cells of the skin as a cosmetic active ingredient and a cosmetic method
to detoxify the skin and / or to prevent or fight against skin aging process.
[0075] In an embodiment of the present disclosure, the compositions of the present
# disclosure, to be used in the form of a topical formulation.
[0076] In an embodiment of the present disclosure, the composition of the present disclosure is to promote skin detoxification and autophagy process in the skin cells; and offer anti-melanogenesis activity. [0077] Although the subject matter has been described with reference to specific
# embodiments, this description is not meant to be construed in a limiting sense. Various modifications of the disclosed embodiments, as well as alternate embodiments of the subject matter, will become apparent to persons skilled in the art upon reference to the description of the subject matter. It is therefore contemplated that such modifications can be made without departing from the spirit
# or scope of the present subject matter as defined. EXAMPLES
[0078] The disclosure will now be illustrated with working examples, which is intended to illustrate the working of disclosure and not intended to take restrictively to imply any limitations on the scope of the present disclosure. Unless defined
# otherwise, all technical and scientific terms used herein have the same meaning as commonly understood to one of ordinary skill in the art to which this disclosure belongs. Although methods and materials similar or equivalent to those described herein can be used in the practice of the disclosed methods and compositions, the exemplary methods, devices and materials are described herein. It is to be understood
# that this disclosure is not limited to particular methods, and experimental conditions described, as such methods and conditions may apply.

[0079] The working examples described herein clearly depict the effect of a combination of dihydroxyresveratrol and pepstatin A at various w/w ratios on skin aging and skin autophagy processes. For this purpose, the present disclosure is directed towards a composition comprising dihydroxyresveratrol and pepstatin A at a ratio range of 8:1 to 12:1, which when used in the suggested ranges is effective in promoting skin autophagy.
[0080] In the present method, a combination of dihydroxyresveratrol and pepstatin A, in isolation and in combination, in defined w/w ratios was tested for its effect on skin health on B16 mouse melanoma cells. B16 melanoma remains an indispensable in-vitro model for various skin related cosmetic research as well as for metastasis studies. In the present method, a shotgun proteomics approach with in-solution protein digestion method followed by LC MS/MS analysis using LTQ Orbitrap Velos was used to analyze the B16 mouse melanoma cells proteome treated under various treatment condition in-vitro (as described in Figure 1). All dilutions mentioned below were performed using water as diluent.
MATERIALS AND METHODS Example 1: Composition
[0081] The composition was prepared by combining all the constituents in different fractions as provided below in Table 1.

The constituents as provided in Table 1, was prepared by obtaining dihydroxyresveratrol, pepstatin A, at least one excipient, and further contacting dihydroxyresveratrol, pepstatin A, with the at least one excipient, to obtain the composition. The process is not based on any particular parameter for preparing the composition. Mixing has to be proper by implementing techniques known in the art. Example 2: Experimental protocol for proteomics study
[0082] The experimentation procedure consists of 4 days. On day 1, the B16 cells were seeded in T 25- flask and incubated in 5% CO2 incubator at 37°C. On day 2, the B16 cells were individually exposed to 10 uM of dihydroxyresveratrol; 1 uM of pepstatin A; and combination of dihydroxyresveratrol (10 uM) + pepstatin A (1 uM).

The cells were further incubated for 72 hours. On day 5, the cells were lysed and processed for proteomic analysis as per the following protocols.
Proteomics experimental protocols: Example 3: Proteomic analysis:
[0083] 30 µg of total protein of each sample (untreated B16 cell lines treated with 10 µM of dihydroxyresveratrol, untreated B16 cell lines treated with 1 µM of pepstatin A, and untreated B16 cell lines treated with a combination of 10 µM of dihydroxyresveratrol and 1 µM of pepstatin A) was subjected to in-solution digestion method, as described in Example 3. The peptide mixtures were separated using a reverse phase column nano-high performance liquid chromatography (HPLC) using pico-frit columns (Thermo) (0.075 mm × 150 mm, C18). The peptides were eluted using a gradient 5 to 90 % of acetonitrile (95%) at a flow rate of 350 nl/min for 60 min. A linear trap quadrapole (LTQ) orbitrap velos mass spectrometer equipped with nano-electron source ionization (ESI) source was used to acquire spectra. A 75-um metal emitter spray tip was used, and the spray voltage was set at 2 kV. The instrument was set under stable spray and conditioned before loading the samples. The instrument was operated in data-dependent mode with dynamic exclusion enabled. The tandem mass spectrometry (MS/MS) spectra on the top 20 most abundant peptide ions in full MS scan were obtained. The normalized collision-induced dissociation (CID) was set at 35% for MS/MS. All MS/MS spectra were searched against the human protein database from uniprot using SEQUEST algorithm incorporated in proteome discoverer 1.4. (using trypsin as cleavage enzyme).
Example 4: In-solution digestion method:
[0084] In-solution protein digestion, is a proteomics protocol where proteins are digested in solution. 100 µg of cell protein extract was resuspended in 47 µl of 6M urea, 50 mM ammonium bicarbonate solution. One µl of 250 mM tris(2-carboxyethyl) phosphine (TCEP) was added in solution and the sample was incubated at 37°C for 30 minutes. Further 2 µl of 625 mM iodoacetamide was added and the sample was incubated in dark at room temperature (25 ± 2ºC) for 45 minutes. Finally, in-solution digestion was carried by addition of 450 µl trypsin in 50 mM

ammonium bicarbonate with protein digest ratio of 50:1. The digested peptides were purified with OASIS 1 ml cartridge system form Waters Scientific (WAT094225).
Example 5: Nano-HPLC & Mass Spectrometry
[0085] The purified / enriched samples were dried and re-suspended in 0.1% formic acid with 5% acetonitrile in MS water. The peptides were loaded onto an EASY-nano LC system (Proxeon). Peptide mixtures were separated on a C18 reverse phase column (PicoFrit capillary column, 75umxl0cm, New Objective) using a linear gradient of solvent A (0.1% formic acid in 5% acetonitrile) and solvent B (0.1% formic acid in 95%acetonitrile) at a flow rate 250 nL/min directly into a LTQ-OrbitrapVelos mass spectrometer (Thermo Scientific, San Jose, CA, USA) with nano-ESI source with spray voltage was set at 1.6 KV. Stable spray condition maintained prior to sample loading. The instrument was operated in data-dependent mode with dynamic exclusion enabled. The MS/MS spectra on the top 20 most abundant peptide ions in full MS scan were obtained. The normalized CID was set at 35% for MS/MS.
Example 6: Data Analysis
[0086] Data analysis pipeline were set to carry out the results data produced by proteome discoverer software version 1.4. The data were searched against the mouse protein database of uniprot. The search was performed choosing trypsin as specific enzyme. A maximum of one missed cleavage was allowed. Peptide (parent ion) tolerance of 2.5 Da and fragment ion tolerance of 1 Da were allowed, oxidation (M) as variable modifications and fixed modification of carbamidomethylation (C) were used.
Results and Discussion
[0087] Figure 1 gives the schematic overview of the work flow of the process carried out in proteomics study. The process steps employed are usual to the global proteomics study, and is well understood by a person skilled in the art. [0088] Figure 2 depicts a graph showing number of proteins identified using Orbitrap MS / proteome discoverer in control, individual and combinatorial treatments in treated B16 cells. For this purpose, a high-throughput proteomic based-mass analysis using Orbitrap MS was used to identify autophagy-related proteins.

From the Figure 2, it can be observed that sum of 2841 proteins were identified across all four samples- (Control - 821, dihydroxyresveratrol treated- 766, pepstatin A treated- 667 and combination of dihydroxyresveratrol + pepstatin A treated - 587). Based on the proteomics data, a further analysis of the proteins as identified in the Figure 2 was performed to understand the effect of the composition in skin autophagy process.
[0089] Based on the results of these studies, biological and cosmeceutical agents useful in the modulation of these proteins and their products were identified and composition for the modulation of autophagy which enhances cell detoxification system were identified.
[0090] Figure 3 depicts the effect of a composition comprising dihydroxyresveratrol and pepstatin A, in isolation and in combination, on sequestome 1 protein levels. Sequestosome-1 is a protein that in humans is encoded by the SQSTM1 gene. Also known as the ubiquitin-binding protein p62, it is an autophagosome cargo protein that targets other proteins that bind to it for selective autophagy. Required both for the formation and autophagic degradation of polyubiquitin-containing bodies, called Aggresome Like Induced Structures (ALIS) and links ALIS to the autophagic machinery. SQSTM1 localizes to autophagosomes by binding to microtubule-associated light chain 3 (LC3) and promoting selective autophagy of proteins. From the Figure 3 it can be observed that dihydroxyresveratrol in isolation at a concentration of 10 µM exhibits a 0.2-fold upregulation in the expression of sequestome 1 protein levels in B16 mouse melanoma cells, whereas pepstatin A in isolation at a concentration of 1µM down regulates the expression of sequestome 1 protein levels. However, unexpectedly and surprisingly, it can be observed that dihydroxyresveratrol and pepstain A in combination, at a ratio of 10:1, causes a significant increase in the expression of sequestome 1 protein levels by 4.2-fold in comparison to the effect of a dihydroxyresveratrol and pepstatin A when used alone. The compositions of the present disclosure exhibit biological activity as modulators (agonists) of autophagy and consequently, can be used in the aging skin condition which occur or are mediated through autophagy as a mechanism. It can be

appreciated that the sum effect of the combinations is a synergistic increase in sequestome 1 protein levels compared to the effect of either ingredients alone. [0091] Figure 4 depicts the effect of a composition comprising dihydroxyresveratrol and pepstatin A, in isolation and in combination, on Mn-superoxide dismutase (MnSOD) protein levels. MnSOD protein levels neutralizes the highly reactive superoxide radical (O0}), the first member in a plethora of mitochondrial reactive oxygen species (ROS). Over the past decades, research has extended the prevailing view of mitochondrion well beyond the generation of cellular energy to include its importance in MnSOD protein levels is vital for healthy aerobic life and the lack of this enzyme is lethal. Knock-out of MnSOD enzyme activity by creating inactive mutants or the complete elimination of MnSOD expression leads to early death in mouse survival and cell death. Retrograde signalling is an important mechanism of communication between mitochondria and nucleus and it impacts a wide spectrum of cellular activities under both normal and pathophysiological conditions. Skin is a highly metabolic tissue with the largest surface area in the body. The skin tissue is exposed to a variety of damaging threats coming from the outer environment, among them oxidative stress. Oxidative stress and altered antioxidant defenses are involved in the pathophysiology of skin aging process. Several studies suggested that topical application of super oxide dismutase reducing the age-related issues in skin. SOD can be incorporated into cosmetics and is available in a topical form, which can be STeadTWV fZdagYZ fZW e][`ve agfWd TSdd[Wd, MfgV[We a` ea_W fab[US^ Xad_e aX MI> indicate absorption and reduction of free radical damage/oxidative stress. From the Figure 4 it can be observed that dihydroxyresveratrol in isolation at a concentration of 10 µM exhibits a 0.13-fold upregulation in the expression of MnSOD protein levels in B16 mouse melanoma cells, whereas pepstatin A in isolation at a concentration of 1µM down regulates the expression of MnSOD protein levels. However, unexpectedly and surprisingly, it can be observed that dihydroxyresveratrol and pepstain A in combination, at a ratio of 10:1, causes a significant increase in the expression of MnSOD protein levels by 1.4-fold in comparison to the effect of a dihydroxyresveratrol and pepstatin A when used alone.

It can be appreciated that the sum effect of the combinations is a synergistic increase in MnSOD protein levels compared to the effect of either ingredients alone. [0092] Figure 5 depicts the effect of a composition comprising dihydroxyresveratrol and pepstatin A, in isolation and in combination, on lysosome-associated membrane glycoprotein 2 protein levels (LAMP). LAMP is a major integral protein of the lysosomal membrane, which plays an important role in the formation of phagosomes, required for the fusion of autophagosomes with lysosomes during autophagy. These proteins act as a receptor in the lysosomal membrane for substrate proteins of chaperone-mediated autophagy. The modulations in the levels of LAMP2 at the
i lysosomal membrane under different conditions have a direct effect on the rates of chaperone-mediated autophagy process. From the Figure 5 it can be observed that dihydroxyresveratrol in isolation at a concentration of 10 µM exhibits a 0.1-fold increase in the expression of LAMP in B16 mouse melanoma cells, whereas pepstatin A in isolation at a concentration of 1µM down regulates the expression of LAMP levels. However, unexpectedly and surprisingly, it can be observed that dihydroxyresveratrol and pepstatin A in combination, at a ratio of 10:1, causes a significant increase in the expression of LAMP levels by 1.6-fold in comparison to the effect of a dihydroxyresveratrol and pepstatin A when used alone. It can be appreciated that the sum effect of the combinations is a synergistic increase in LAMP
i levels compared to the effect of either ingredients alone.
[0093] Figure 6 depicts the effect of a composition comprising dihydroxyresveratrol and pepstatin A, in isolation and in combination, on lysosomal alpha glucosidase protein (GAA) levels. GAA the sole hydrolase responsible for the breakdown of glycogen to glucose in the acidic milieu of the lysosome. The lack or insufficient activity of GAA results in accumulation of lysosomal glycogen that primarily affects cardiac and skeletal muscles. Enzyme replacement therapy (ERT) with recombinant human GAA (rhGAA; Myozyme®, alglucosidase alfa, Genzyme Corp., Framingham, MA) is the first approved therapy for this devastating disorder. Although ERT has proven to be reasonably successful with infants, it's effect on
i skeletal muscle is falls short of expectations. Infact, it has been observed both in humans and in GAA-/- (GAA deficient) mice that glycogen accumulation persists

even when the enzyme activity reaches normal or near normal levels in muscle. This suggests that some intrinsic properties of muscle cells play a role. Itvs been found that muscle fibers in the GAA-/- mice and in patients with the disease contain large pools of autophagic debris in addition to the enlarged glycogen-filled lysosomes. In
# the GAA-/- mice, this autophagic build up is seen in therapy-resistant fast muscles but not in slow muscles which respond well to therapy. From the Figure 6 it can be observed that dihydroxyresveratrol in isolation at a concentration of 10 µM exhibits a 0.87-fold increase in the expression of GAA in B16 mouse melanoma cells, whereas pepstatin A in isolation at a concentration of 1µM increases the expression
# of GAA by 0.5-fold. However, unexpectedly and surprisingly, it can be observed that dihydroxyresveratrol and pepstatin A in combination, at a ratio of 10:1, causes a significant increase in the expression of GAA levels by 2.3-fold in comparison to the effect of a dihydroxyresveratrol and pepstatin A when used alone. It can be appreciated that the sum effect of the combinations is a synergistic increase in GAA
# protein levels compared to the effect of either ingredients alone. [0094] Figure 7 depicts the effect of a composition comprising dihydroxyresveratrol and pepstatin A, in isolation and in combination, on chymotrypsinogen protein levels. Chymotrypsinogen B encodes a member of the serine protease family of enzymes and forms a principal precursor of the pancreatic proteolytic enzymes. The
# encoded preproprotein is synthesized in the acinar cells of the pancreas and secreted into the small intestine where it undergoes proteolytic activation to generate a functional enzyme. This gene is located adjacent to a related chymotrypsinogen gene. This gene encodes distinct isoforms, some or all of which may undergo similar processing to generate the mature protein. However Miao et. et., J Biol. Chem. 2008
# Mar 28; 283(13):8218-28 study demonstrated for the first time that chymotrypsin B is not only restricted to the pancreas but can function intracellularly as a pro-apoptotic protease. Translocation of lysosomal chymotrypsin B into cytosol was triggered by apoptotic stimuli such as tumor necrosis factor-alpha, and intracellular delivery of chymotrypsin B protein induced apoptotic cell death with a potency
# comparable with cathepsin B, suggestive of a lysosomal-mitochondrial pathway to apoptosis regulated by chymotrypsin B following its release. Noteworthily, either

knockdown of chymotrypsin B expression by RNA interference or pretreatment with chymotrypsin B inhibitor N-p-tosyl-L-phenylalanine chloromethyl ketone significantly reduced tumor necrosis factor-alpha-induce apoptosis. From the Figure 7 it can be observed that dihydroxyresveratrol in isolation at a concentration of 10 µM exhibits a 0.4-fold increase in the expression of chymotrypsinogen B in B16 mouse melanoma cells, whereas pepstatin A in isolation at a concentration of 1µM increases the expression of chymotrypsinogen B by 0.9-fold. However, unexpectedly and surprisingly, it can be observed that dihydroxyresveratrol and pepstatin A in combination, at a ratio of 10:1, causes a significant increase in the expression of chymotrypsinogen B levels by 3.3-fold in comparison to the effect of a dihydroxyresveratrol and pepstatin A when used alone. It can be appreciated that the sum effect of the combinations is a synergistic increase in chymotrypsinogen B levels compared to the effect of either ingredients alone.
[0095] Figure 8 depicts the effect of a composition comprising dihydroxyresveratrol and pepstatin A, in isolation and in combination, on ubiquitin carboxyterminal hydrolase protein levels (UCHL1). UCHL1 encoded by this gene belongs to the peptidase C12 family. This enzyme is a thiol protease that hydrolyzes a peptide bond at the C-terminal glycine of ubiquitin. This gene is specifically expressed in the neurons and in cells of the diffuse neuroendocrine system. Ubiquitination modification has been shown to play a key role in autophagy. Increasing studies reported the involvement of de-ubiquitinating enzymes (DUBs) in autophagy pathway. From the Figure 8 it can be observed that dihydroxyresveratrol in isolation at a concentration of 10 µM exhibits a 1-fold decrease in the expression of UCHL1 protein levels in B16 mouse melanoma cells, whereas pepstatin A in isolation at a concentration of 1µM down regulates the expression of UCHL1 protein levels by approximately 2-fold. However, unexpectedly and surprisingly, it can be observed that dihydroxyresveratrol and pepstain A in combination, at a ratio of 10:1, causes a decrease in the expression of UCHL1 protein levels by 2.63-fold, the decrease being lesser than the combinatorial effect of a dihydroxyresveratrol and pepstatin A when used alone.
Negative data

[0096] Proteins such as sequestome 1, Mn-superoxide dismutase, lysosome-associated membrane glycoprotein 2, lysosomal alpha glucosidase and chymotrypsinogen B which are known to play key role in maintaining autophagy, showed synergistic up-regulation of expression, and similarly ubiquitin carboxyterminal hydrolase was down regulated in our study as shown in Figure 3-8. Although GST P1 protein levels were unfavorably down regulated, the other proteins, namely, sequestome 1, Mn-superoxide dismutase, lysosome-associated membrane glycoprotein 2, lysosomal alpha glucosidase and chymotrypsinogen B, are deregulated in the autophagy conditions directly or indirectly affecting skin aging and the above combination synergistically modulated the protein levels in a favorable way.
Advantages of the present disclosure
[0097] The present disclosure reveals that a combination of dihydroxyresveratrol and pepstatin A at specific w/w ratios is effective in promoting skin autophagy process. Unlike the conventionally-available cosmetic compositions and complicated medical procedures that are suited for treating aged skin, the compositions of the present disclosure are highly advantageous in that they could be applied topically, thereby circumventing the need for complicated invasive, painful, and costly medical procedures for improving skin health.

I/We Claim:
1. A composition comprising:
a) dihydroxyresveratrol; and
b) pepstatin A,
wherein dihydroxyresveratrol, and pepstatin A w/w ratio is in a range of 8:1 to 12:1.
2. The composition as claimed in claim 1, wherein dihydroxyresveratrol, and pepstatin A w/w ratio is 10:1.
3. The composition as claimed in claim 1, wherein dihydroxyresveratrol has weight percentage in a range of 0.5 to 1.6% with respect to the composition.
4. The composition as claimed in claim 1, wherein pepstatin A has weight percentage in a range of 0.05 s 0.2% with respect to the composition.
5. The composition as claimed in any one of the claims 1-4 upregulates the expression of Mn-superoxide dismutase.
6. The composition as claimed in any one of the claims 1-4 upregulates the expression of sequestome 1 protein.
7. The composition as claimed in any one of the claims 1-4 upregulates the expression of lysosome-associated membrane glycoprotein 2.
8. The composition as claimed in any one of the claims 1-4 upregulates the expression of lysosomal alpha glucosidase.
9. The composition as claimed in any one of the claims 1-4 upregulates the expression of chymotrypsinogen B.
10. The composition as claimed in any one of the claims 1-4 downregulates the expression of ubiquitin carboxyterminal hydrolase.
11. The composition as claimed in any one of the claims 1-10, wherein the composition further comprises at least one excipient selected from diluent, preservative, viscosity modifier, bulking agent, chelating agent, stabilizing agent, humectant, surfactant, pH modifier, perfume, texture enhancer, emollient, skin conditioning agent, antioxidant, and combinations thereof.
12. The composition as claimed in claim 11, said composition comprising:

a) dihydroxyresveratrol having a concentration in a range of 8 s 12 µM with respect to the composition;
b) pepstatin A having a concentration in a range of 0.8 s 1.2 µM with respect to the composition; and
c) at least one diluent selected from a group consisting of water, glycerol, and combinations thereof.
13. A process for preparing the composition as claimed in claim 1, said process
comprising:
a) obtaining dihydroxyresveratrol;
b) obtaining pepstatin A; and
c) contacting dihydroxyresveratrol and pepstatin A, to obtain the composition.
14. A process for preparing the composition as claimed in claim 11, said process
comprising:
a) obtaining dihydroxyresveratrol;
b) obtaining pepstatin A;
c) obtaining the at least one excipient; and
d) contacting dihydroxyresveratrol, pepstatin A, with the at least one excipient, to obtain the composition.
15. The composition as claimed in any one of the claims 1 to 11, wherein the
composition is effective in promoting skin autophagy process.