Abstract: The present disclosure relates to composition comprising: oxyresveratrol; dihydrooxyresveratrol; and catechin, wherein oxyresveratrol, dihydrooxyresveratrol, and catechin w/w/w ratio is in the range of 1-2:1-2:1-2. The composition exhibits skin benefits by decreasing expression of proteins related to skin pigmentation, inflammation, and skin-ageing. A formulation comprising the composition as disclosed herein has also been provided along with a process for preparing the formulation and composition.
FIELD OF INVENTION
[001] The present disclosure broadly relates to field of cosmetics and particularly relates to a composition comprising oxyresveratrol, dihydrooxyresveratrol, and catechin for skin benefits.
BACKGROUND OF INVENTION
[002] Skin is the largest organ of the body and serves several vital functions, including body protection, absorption, secretion, excretion, thermo-regulation, pigment synthesis, sensory perception and immunity. It is constantly exposed to harmful environments and extreme conditions, such as ultra-violet radiation, urban pollution, industrial contamination, pathogenic attacks, allergenic challenges, carcinogenic substances etc. Hence, the skin regularly needs topical treatment, which is usually provided by dermo-cosmetics, i.e., cosmetic preparations and/or dermal pharmaceutics.
[003] Skin aging is natural process associated with a number of pathophysiological conditions that can reduce quality of life and longevity. Skin ageing is influenced by two types of ageing - external ageing and internal ageing. Intrinsic ageing appears to be a manifestation of natural ageing process and is genetically determined. On the other hand, extrinsic ageing is a manifestation of external damage and exposure to harsh environmental components. [004] Skin pigmentation is tightly linked with the transfer of melanosome from melanocytes to neighboring keratinocytes. The epidermis, the outer layer of skin, consists mainly of two cell types, keratinocytes and melanocytes. Melanocytes synthesize and store melanin pigment within membrane-enclosed lysosome-related organelles (LROs) called melanosomes. However, the pigment that one sees in skin is primarily within keratinocytes, the recipient cells for melanin. Melanin-filled melanosomes are transferred from the ends of dendrites to keratinocytes (surrounding cells in the skin) for shipment to the surface of the skin. In spite of the large variations in skin colour that exist among people from different parts of the world, everyone has exactly the same number of melanocytes in their skin. The
difference in the amount of melanin in a person's skin is due to primarily (1) how active the melanocytes are, (2) how much melanin they synthesize and (3) how efficiently they transport melanin-filled melanosomes to keratinocytes throughout the skin.
[005] Melanogenesis is a complex metabolic pathway controlled by a family of enzymes known as tyrosinase-related proteins, which are synthesized and glycosylated in the ER and Golgi and then further trafficked to melanosomes where they synthesize and deposit melanin. HSP90 family, also known as HSP90 P is a molecular chaperone localized in the lumen of the endoplasmic reticulum (ER) and is important for protein maturation and homeostasis.
[006] US8568751B1 discloses a cosmeceutical composition that delivers both short and long-term improvement in the appearance of skin. The composition includes, as required ingredients, at least a suspension of a powder of an aliphatic polyester copolymer, a cross-linked silicone elastomer, and one or more components that are hydrolyzates and/or acylated short chain peptides. [007] WO2009088109A1 discloses a skin-whitening composition, characterized by comprising diosgenin as an active ingredient. The composition comprising diosgenin can be safely used without side effects, and suppress melanin synthesis to inhibit pigmentation, thereby being used for improving melasma or freckles, and whitening skin.
[008] Although compositions for skin whitening and anti-ageing are known in the prior art, but there is a dearth of compositions that can target molecular mechanisms of both skin ageing and skin pigmentation, thereby effectively providing a fair and healthy skin.
SUMMARY OF THE INVENTION
[009] In an aspect of the present invention, there is provided a composition comprising: (a) oxyresveratrol; (b) dihydrooxyresveratrol; and (c) catechin, wherein oxyresveratrol, dihydrooxyresveratrol, and catechin w/w ratio is in the range of 1-2:1-2:1-2.
[0010] In an aspect of the present invention, there is provided a process for preparing the composition comprising: (a) oxyresveratrol; (b)
dihydrooxyresveratrol; and (c) catechin, wherein oxyresveratrol, dihydrooxyresveratrol, and catechin w/w ratio is in the range of 1-2:1-2:1-2, said process comprising: (i) obtaining oxyresveratrol; (ii) obtaining dihydrooxyresveratrol; (iii) obtaining catechin; and (iv) contacting oxyresveratrol, dihydrooxyresveratrol, and catechin to obtain the composition. [0011] 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 ACCOMPANYING DRAWINGS
[0012] The following drawings form a part of the present specification and are
included to further illustrate aspects of the present disclosure. The disclosure may
be better understood by reference to the drawings in combination with the detailed
description of the specific embodiments presented herein.
[0013] Figure 1 depicts the effect of oxyresveratrol, dihydrooxyresveratrol and
catechin and their composition on melanin inhibition assay in co culture of B16 and
HacaTs cells, in accordance with an embodiment of the present disclosure.
[0014] Figure 2 depicts the effect of oxyresveratrol, dihydrooxyresveratrol and
catechin and their composition on HSP-90 P protein expression identified using
orbitrap mass analyzer based on proteomics method, in accordance with an
embodiment of the present disclosure.
[0015] Figure 3 depicts the effect of oxyresveratrol, dihydrooxyresveratrol and
catechin and their composition on HSP-70 P protein expression identified using
orbitrap mass analyzer based on proteomics method, in accordance with an
embodiment of the present disclosure.
[0016] Figure 4 depicts the effect of oxyresveratrol, dihydrooxyresveratrol and
catechin and their composition on V-type proton ATase subunit El protein
expression in fold changes identified using orbitrap mass analyzer based on proteomics method, in accordance with an embodiment of the present disclosure. [0017] Figure 5 depicts the effect of oxyresveratrol dihydrooxyresveratrol and catechin and their composition on basigin (CD 147) protein expression in fold changes identified using orbitrap mass analyzer based on proteomics method, in accordance with an embodiment of the present disclosure.
[0018] Figure 6 depicts the effect of oxyresveratrol dihydrooxyresveratrol and catechin and their composition on annexin A5 protein expression in fold changes identified using orbitrap mass analyzer based on proteomics method, in accordance with an embodiment of the present disclosure.
[0019] Figure 7 depicts the effect of oxyresveratrol 6'7'4-trihydro-isoflavone and catechin and their composition on basigin (CD 147) protein expression in fold changes identified using orbitrap mass analyzer based on proteomics method, in accordance with an embodiment of the present disclosure.
DETAILED DESCRIPTION OF THE INVENTION
[0020] 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
[0021] 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.
[0022] 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.
[0023] 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".
[0024] 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.
[0025] The term "including" is used to mean "including but not limited to". "Including" and "including but not limited to" are used interchangeably. [0026] 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 ratio range of about 1-2:1-2:1-2 should be interpreted to include not only the explicitly recited limits of about 1 :-2:1-2:1-2, but also to include sub-ranges, such as, 1:2:1, 2:1:1, 1:1:2, 1:1:1, and so forth, as well as individual amounts, including fractional amounts, within the specified ranges, such as 1.33:1:1, 1:1.33:1, 1:1:1.33, 1.5:1:1, 1.67:1:1, for example.
[0027] For the purposes of the present document, polymers, gum base, chelating agents, emulsifiers, surfactants, humectants, solvents, antimicrobial agents, moisturizers, fragrance, as mentioned herein, can be selected from any of the respective components well known in the art.
[0028] As discussed in the background section, in order to be effective, a composition should be able to act at molecular levels. Primary aim of this disclosure is to arrive at a composition that can intervene with molecular mechanisms to provide anti-ageing and skin-whitening benefits.
[0029] In order to target molecular mechanisms of ageing and pigmentation, a wide range of targets need to be identified and tested. A proteomics study from other group showed that the chaperone HSP-90 P is also present within melanosomes and studies revealed that Hsp-90 p positively regulates melanogenesis and melanosome development by facilitating tyrosinase trafficking and enzymatic function via chaperoning the Wnt canonical pathway. Hsp70 family proteins generally function as molecular chaperones for the post-translational modification of target proteins and to prevent aggregate formation, promoting maintenance of cellular homeostasis following cellular stresses. In addition to promoting optimal protein folding, Hsp70 proteins also function in a variety of cellular biological processes such as melanogenesis.
[0030] The V-ATPase is a proton pump that creates an acidic medium, necessary for lysosome function and vesicular traffic. It is also essential for several developmental processes. Many enzymes, like the V-ATPase, are assemblies of multiple subunits, in which each one performs a specific function required to achieve full activity. The V-ATPase complex is oriented in the membrane in such a way that it pumps protons from the cytoplasm out of the cell or to the interior of certain organelles. V-ATPase function must be essential for melanosome biogenesis, the lack of such organelles cause the pigment dilution phenotype and may also induce melanocyte degradation, which is observed in the form of melanin spots in the zebra fish pigment dilution mutants.
[0031] Basigin (BSG), also called CD147 or EMMPRIN, is a transmembrane glycoprotein that belongs to the immunoglobulin superfamily. Basigin, also referred to in the art as extracellular matrix metalloproteinase inducer ("EMMPRIN") and designated cluster of differentiation 147 (CD 147), is a cell surface glycoprotein expressed by tumor and many other cell types and is involved in intercellular recognition. Basigin is a type I integral membrane receptor that belongs to the immunoglobulin superfamily and has numerous ligands, including the cyclophilin (CyP) proteins Cyp-A and CyP-B and certain integrins. BSG has a variety of functions, including inducing matrix metalloproteinase production and regulating spermatogenesis, monocarboxylate transporter expression, the
responsiveness of lymphocytes, embryo implantation, neural network formation, and tumor progression. Basigin is important for growth, survival and invasion of tumour cells, anti- basigin reagents, such as anti- basigin antibodies, peptide fragments of basigin and siRNAs directed to basigin are being explored as antitumor therapeutics.
[0032] Annexin 5 is a phospholipase A2 and protein kinase C inhibitory protein with calcium channel activity and a potential role in cellular signal transduction, inflammation, growth and differentiation. This protein belongs to the annexin family of calcium-dependent phospholipid binding proteins some of which have been implicated in membrane-related events along exocytotic and endocytotic pathways. ANX5 is also observed in aged human skin where exclusively detected in DNA damage foci-positive/Ki-67-negative cells.
[0033] The aim of the present disclosure is to offer a new composition to protect
skin ageing and to offer anti melanogenesis activity. The working hypothesis for
this study is that skin aging results from the dysregulation of key regulatory
proteins (i.e., protein signatures) which in turn, interacting and overlapping
networks and intracellular pathways. Dysregulation of protein functions leads to
physiological aging of tissues, cells and subcellular components. The present study
provides information that will guide future research and suggest new therapies for
preventing, mitigating or treating skin pathologies related to aging.
[0034] The present disclosure provides a composition comprising oxyresveratrol,
dihydrooxyresveratrol, and catechin, wherein oxyresveratrol,
dihydrooxyresveratrol, and catechin w/w ratio is in the range of 1-2:1-2:1-2. The effect of the present composition in providing anti-ageing and skin-whitening benefits have been shown by providing working examples in the present disclosure. [0035] Oxyresveratrol is a stilbenoid described as a powerful inhibitor of tyrosinase and proposed as skin-whitening and anti-browning agent. [0036] Dihydrooxyresveratrol also known as 2, 3', 4, 5'-Tetrahydroxystilbene, is a new derivative of oxyresveratrol having a more potent tyrosinase inhibition activity than oxyresveratrol.
[0037] Catechin is a naturally occurring flavanol or flavan-3-ol and a well-demonstrated antioxidant phytochemical. Catechin is a constituent of several medicinal plants found throughout.
[0038] The present disclosure discloses synergistic effect of the composition comprising three actives as mentioned in the above paragraphs, in providing anti-ageing and skin-whitening benefits. The first aspect of the present disclosure relates to a composition which is capable of modulating the activity or expression of heat shock protein 90 beta, HSP -70 and V-type proton ATPase. The second aspect of the present disclosure is to display the modulation of the expression of Basigin and Annexin A5 by the composition as described herein. [0039] 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. [0040] 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. [0041] In an embodiment of the present disclosure, there is provided a composition comprising: (a) oxyresveratrol; (b) dihydrooxyresveratrol; and (c) catechin, wherein oxyresveratrol, dihydrooxyresveratrol, and catechin w/w/w ratio is in the range of 1-2:1-2:1-2.
[0042] In an embodiment of the present disclosure, there is provided a composition comprising: (a) oxyresveratrol; (b) dihydrooxyresveratrol; and (c) catechin, wherein oxyresveratrol, dihydrooxyresveratrol, and catechin w/w/w ratio is in the range of 1.33:1:1.
[0043] In an embodiment of the present disclosure, there is provided a composition comprising: (a) oxyresveratrol; (b) dihydrooxyresveratrol; and (c) catechin, wherein oxyresveratrol, dihydrooxyresveratrol, and catechin w/w/w ratio is in the
range of 1-1.5:1-1.5:1-1.5. In another embodiment of the present disclosure, oxyresveratrol, dihydrooxyresveratrol, and catechin w/w/w ratio is in the range of 1-1.4:1-1.4:1-1.4. In yet another embodiment of the present disclosure, oxyresveratrol, dihydrooxyresveratrol, and catechin w/w/w ratio is in the range of 1.1-1.35:1.1-1.35:1.1-1.35.
[0044] In an embodiment of the present disclosure, there is provided a composition comprising: (a) oxyresveratrol; (b) dihydrooxyresveratrol; and (c) catechin, wherein oxyresveratrol, dihydrooxyresveratrol, and catechin w/w ratio is in the range of 1.55-2:1.55-2:1.55-2. In another embodiment of the present disclosure, oxyresveratrol, dihydrooxyresveratrol, and catechin w/w/w ratio is in the range of 1.65-1.90:1.65-1.90:1.65-1.90. In yet another embodiment of the present disclosure, oxyresveratrol, dihydrooxyresveratrol, and catechin w/w/w ratio is in the range of 1.75-1.85:1.75-1.85:1.75-1.85.
[0045] In an embodiment of the present disclosure, there is provided a composition comprising: (a) oxyresveratrol; (b) dihydrooxyresveratrol; and (c) catechin, wherein oxyresveratrol, dihydrooxyresveratrol, and catechin w/w/w ratio is in the range of 1:1:2. In another embodiment of the present disclosure, oxyresveratrol, dihydrooxyresveratrol, and catechin w/w/w ratio is in the range of 1:2:1. In yet another embodiment of the present disclosure, oxyresveratrol, dihydrooxyresveratrol, and catechin w/w/w ratio is in the range of 2:1:1. [0046] In an embodiment of the present disclosure, there is provided a composition comprising: (a) oxyresveratrol; (b) dihydrooxyresveratrol; and (c) catechin, wherein oxyresveratrol, dihydrooxyresveratrol, and catechin w/w ratio is in the range of 1.33:1:1. In another embodiment of the present disclosure, oxyresveratrol, dihydrooxyresveratrol, and catechin w/w/w ratio is in the range of 1:1.33:1. In yet another embodiment of the present disclosure, oxyresveratrol, dihydrooxyresveratrol, and catechin w/w/w ratio is in the range of 1:1:1.33. [0047] In an embodiment of the present disclosure, there is provided a composition comprising: (a) oxyresveratrol; (b) dihydrooxyresveratrol; and (c) catechin, wherein oxyresveratrol, dihydrooxyresveratrol, and catechin w/w/w ratio is in the range of 1-2:1-2:1-2, and wherein oxyresveratrol has a weight percentage in the
range of 0.30% - 0.50% with respect to the composition. In another embodiment of the present disclosure, oxyresveratrol has a weight percentage in the range of 0.35%) - 0.45%) with respect to the composition. In yet another embodiment of the present disclosure, oxyresveratrol has a weight percentage in the range of 0.38%> -0.42%o with respect to the composition.
[0048] In an embodiment of the present disclosure, there is provided a composition comprising: (a) oxyresveratrol; (b) dihydrooxyresveratrol; and (c) catechin, wherein oxyresveratrol, dihydrooxyresveratrol, and catechin w/w/w ratio is in the range of 1-1.66:1-2:1-2, and wherein oxyresveratrol has a weight percentage in the range of 0.30%> - 0.50% with respect to the composition. In another embodiment of the present disclosure, oxyresveratrol has a weight percentage in the range of 0.35%o - 0.45%) with respect to the composition. In yet another embodiment of the present disclosure, oxyresveratrol has a weight percentage in the range of 0.38%> -0.42%o with respect to the composition.
[0049] In an embodiment of the present disclosure, there is provided a composition comprising: (a) oxyresveratrol; (b) dihydrooxyresveratrol; and (c) catechin, wherein oxyresveratrol, dihydrooxyresveratrol, and catechin w/w/w ratio is 1.33:1:1, and wherein oxyresveratrol has a weight percentage in the range of 0.30%> - 0.50%) with respect to the composition. In another embodiment of the present disclosure, oxyresveratrol has a weight percentage in the range of 0.35% - 0.45% with respect to the composition. In yet another embodiment of the present disclosure, oxyresveratrol has a weight percentage in the range of 0.38%> - 0.42% with respect to the composition.
[0050] In an embodiment of the present disclosure, there is provided a composition comprising: (a) oxyresveratrol; (b) dihydrooxyresveratrol; and (c) catechin, wherein oxyresveratrol, dihydrooxyresveratrol, and catechin w/w/w ratio is in the range of 1-2:1-2:1-2, and wherein dihydrooxyresveratrol has a weight percentage in the range of 0.20% - 0.40% with respect to the composition. In another embodiment of the present disclosure, dihydrooxyresveratrol has a weight percentage in the range of 0.25% - 0.35% with respect to the composition. In yet
another embodiment of the present disclosure, dihydrooxyresveratrol has a weight percentage in the range of 0.28% - 0.32% with respect to the composition. [0051] In an embodiment of the present disclosure, there is provided a composition comprising: (a) oxyresveratrol; (b) dihydrooxyresveratrol; and (c) catechin, wherein oxyresveratrol, dihydrooxyresveratrol, and catechin w/w/w ratio is in the range of 1-1.66:1-2:1-2, and wherein dihydrooxyresveratrol has a weight percentage in the range of 0.20% - 0.40% with respect to the composition. In another embodiment of the present disclosure, dihydrooxyresveratrol has a weight percentage in the range of 0.25% - 0.35% with respect to the composition. In yet another embodiment of the present disclosure, dihydrooxyresveratrol has a weight percentage in the range of 0.28% - 0.32% with respect to the composition. [0052] In an embodiment of the present disclosure, there is provided a composition comprising: (a) oxyresveratrol; (b) dihydrooxyresveratrol; and (c) catechin, wherein oxyresveratrol, dihydrooxyresveratrol, and catechin w/w/w ratio is in the range of 1.33:1:1, and wherein dihydrooxyresveratrol has a weight percentage in the range of 0.20% - 0.40% with respect to the composition.
[0053] In an embodiment of the present disclosure, there is provided a composition comprising: (a) oxyresveratrol; (b) dihydrooxyresveratrol; and (c) catechin, wherein oxyresveratrol, dihydrooxyresveratrol, and catechin w/w/w ratio is in the range of 1-2:1-2:1-2, and wherein oxyresveratrol has a weight percentage in the range of 0.30% - 0.50% with respect to the composition, and dihydrooxyresveratrol has a weight percentage in the range of 0.20% - 0.40% with respect to the composition. In another embodiment of the present disclosure, oxyresveratrol has a weight percentage in the range of 0.35% - 0.45% with respect to the composition, and dihydrooxyresveratrol has a weight percentage in the range of 0.25%) - 0.35%) with respect to the composition. In yet another embodiment of the present disclosure, oxyresveratrol has a weight percentage in the range of 0.38%) - 0.42%) with respect to the composition, and dihydrooxyresveratrol has a weight percentage in the range of 0.28% - 0.32% with respect to the composition. [0054] In an embodiment of the present disclosure, there is provided a composition comprising: (a) oxyresveratrol; (b) dihydrooxyresveratrol; and (c) catechin,
wherein oxyresveratrol, dihydrooxyresveratrol, and catechin w/w/w ratio is in the range of 1-2:1-2:1-2, and wherein catechin has a weight percentage in the range of 0.20% - 0.40% with respect to the composition. In another embodiment of the present disclosure, catechin has a weight percentage in the range of 0.25% - 0.35% with respect to the composition. In yet another embodiment of the present disclosure, catechin has a weight percentage in the range of 0.28% - 0.32% with respect to the composition.
[0055] In an embodiment of the present disclosure, there is provided a composition comprising: (a) oxyresveratrol; (b) dihydrooxyresveratrol; and (c) catechin, wherein oxyresveratrol, dihydrooxyresveratrol, and catechin w/w/w ratio is in the range of 1-2:1-2:1-2, and wherein oxyresveratrol has a weight percentage in the range of 0.30% - 0.50% with respect to the composition, and catechin has a weight percentage in the range of 0.20% - 0.40% with respect to the composition. In another embodiment of the present disclosure, oxyresveratrol has a weight percentage in the range of 0.35% - 0.45% with respect to the composition, and catechin has a weight percentage in the range of 0.25% - 0.35% with respect to the composition. In yet another embodiment of the present disclosure, oxyresveratrol has a weight percentage in the range of 0.38% - 0.42% with respect to the composition, and catechin has a weight percentage in the range of 0.28% - 0.32% with respect to the composition.
[0056] In an embodiment of the present disclosure, there is provided a composition comprising: (a) oxyresveratrol; (b) dihydrooxyresveratrol; and (c) catechin, wherein oxyresveratrol, dihydrooxyresveratrol, and catechin w/w/w ratio is in the range of 1-2:1-2:1-2, and wherein dihydrooxyresveratrol has a weight percentage in the range of 0.20% - 0.40% with respect to the composition, and catechin has a weight percentage in the range of 0.20% - 0.40% with respect to the composition. In another embodiment of the present disclosure, dihydrooxyresveratrol has a weight percentage in the range of 0.25% - 0.35% with respect to the composition, and catechin has a weight percentage in the range of 0.25% - 0.35% with respect to the composition. In yet another embodiment of the present disclosure, dihydrooxyresveratrol has a weight percentage in the range of 0.28% - 0.32% with
respect to the composition, and catechin has a weight percentage in the range of 0.28% - 0.32% with respect to the composition.
[0057] In an embodiment of the present disclosure, there is provided a composition comprising: (a) oxyresveratrol; (b) dihydrooxyresveratrol; and (c) catechin, wherein oxyresveratrol, dihydrooxyresveratrol, and catechin w/w/w ratio is in the range of 1-2:1-2:1-2, and wherein oxyresveratrol has a weight percentage in the range of 0.30% - 0.50% with respect to the composition, dihydrooxyresveratrol oxyresveratrol has a weight percentage in the range of 0.20% - 0.40% with respect to the composition, and catechin has a weight percentage in the range of 0.20% -0.40%) with respect to the composition. In another embodiment of the present disclosure, oxyresveratrol has a weight percentage in the range of 0.35% - 0.45% with respect to the composition, dihydrooxyresveratrol oxyresveratrol has a weight percentage in the range of 0.25% - 0.35% with respect to the composition, and catechin has a weight percentage in the range of 0.25% - 0.35% with respect to the composition. In yet another embodiment of the present disclosure, oxyresveratrol has a weight percentage in the range of 0.38% - 0.42% with respect to the composition, dihydrooxyresveratrol oxyresveratrol has a weight percentage in the range of 0.28% - 0.32% with respect to the composition, and catechin has a weight percentage in the range of 0.28% - 0.32% with respect to the composition. [0058] In an embodiment of the present disclosure, there is provided a composition comprising: (a) oxyresveratrol; (b) dihydrooxyresveratrol; and (c) catechin, wherein oxyresveratrol, dihydrooxyresveratrol, and catechin w/w/w ratio is in the range of 1-1.66:1-2:1-2, and wherein oxyresveratrol has a weight percentage in the range of 0.30% - 0.50% with respect to the composition, dihydrooxyresveratrol oxyresveratrol has a weight percentage in the range of 0.20% - 0.40% with respect to the composition, and catechin has a weight percentage in the range of 0.20% -0.40%) with respect to the composition. In another embodiment of the present disclosure, oxyresveratrol has a weight percentage in the range of 0.35% - 0.45% with respect to the composition, dihydrooxyresveratrol oxyresveratrol has a weight percentage in the range of 0.25% - 0.35% with respect to the composition, and catechin has a weight percentage in the range of 0.25% - 0.35% with respect to the
composition. In yet another embodiment of the present disclosure, oxyresveratrol has a weight percentage in the range of 0.38% - 0.42% with respect to the composition, dihydrooxyresveratrol oxyresveratrol has a weight percentage in the range of 0.28% - 0.32% with respect to the composition, and catechin has a weight percentage in the range of 0.28% - 0.32% with respect to the composition. [0059] In an embodiment of the present disclosure, there is provided a composition comprising: (a) oxyresveratrol; (b) dihydrooxyresveratrol; and (c) catechin, wherein oxyresveratrol, dihydrooxyresveratrol, and catechin w/w/w ratio is 1.33:1:1, and wherein oxyresveratrol has a weight percentage of 0.40% with respect to the composition, dihydrooxyresveratrol oxyresveratrol has a weight percentage of 0.30% with respect to the composition, and catechin has a weight percentage of 0.30% with respect to the composition.
[0060] In an embodiment of the present disclosure, there is provided a composition comprising: (a) oxyresveratrol; (b) dihydrooxyresveratrol; (c) catechin; and (d) at least one excipient, wherein oxyresveratrol, dihydrooxyresveratrol, and catechin w/w/w ratio is in the range of 1-2:1-2:1-2, and the at least one excipient is selected from the group consisting of polymer, gum base, chelating agent, emulsifier, surfactant, humectant, solvent, antimicrobial agent, moisturizer, water, fragrance, dimethyl sulfoxide (DMSO), bulking agent, and combinations thereof. [0061] In an embodiment of the present disclosure, there is provided a composition comprising: (a) oxyresveratrol; (b) dihydrooxyresveratrol; (c) catechin; and (d) at least one excipient, wherein oxyresveratrol, dihydrooxyresveratrol, and catechin w/w/w ratio is 1.33:1:1, and the at least one excipient is selected from the group consisting of polymer, gum base, chelating agent, emulsifier, surfactant, humectant, solvent, antimicrobial agent, moisturizer, water, fragrance, DMSO, bulking agent, and combinations thereof.
[0062] In an embodiment of the present disclosure, there is provided a composition comprising: (a) oxyresveratrol; (b) dihydrooxyresveratrol; (c) catechin; and (d) at least one excipient, wherein oxyresveratrol, dihydrooxyresveratrol, and catechin w/w/w ratio is in the range of 1-2:1-2:1-2, and the at least one excipient is selected from the group consisting of polymer, gum base, chelating agent, emulsifier,
surfactant, humectant, solvent, antimicrobial agent, moisturizer, water, fragrance, DMSO, bulking agent, and combinations thereof, and wherein oxyresveratrol has a weight percentage in the range of 0.30% - 0.50% with respect to the composition. [0063] In an embodiment of the present disclosure, there is provided a composition comprising: (a) oxyresveratrol; (b) dihydrooxyresveratrol; (c) catechin; and (d) at least one excipient, wherein oxyresveratrol, dihydrooxyresveratrol, and catechin w/w/w ratio is in the range of 1-2:1-2:1-2, and the at least one excipient is selected from the group consisting of polymer, gum base, chelating agent, emulsifier, surfactant, humectant, solvent, antimicrobial agent, moisturizer, water, fragrance, DMSO, bulking agent, and combinations thereof, and wherein dihydrooxyresveratrol has a weight percentage in the range of 0.20% - 0.40% with respect to the composition.
[0064] In an embodiment of the present disclosure, there is provided a composition comprising: (a) oxyresveratrol; (b) dihydrooxyresveratrol; (c) catechin; and (d) at least one excipient, wherein oxyresveratrol, dihydrooxyresveratrol, and catechin w/w/w ratio is in the range of 1-2:1-2:1-2, and the at least one excipient is selected from the group consisting of polymer, gum base, chelating agent, emulsifier, surfactant, humectant, solvent, antimicrobial agent, moisturizer, water, fragrance, DMSO, bulking agent, and combinations thereof, and wherein catechin has a weight percentage in the range of 0.20% - 0.40% with respect to the composition. [0065] In an embodiment of the present disclosure, there is provided a composition comprising: (a) oxyresveratrol; (b) dihydrooxyresveratrol; (c) catechin; and (d) at least one excipient, wherein oxyresveratrol, dihydrooxyresveratrol, and catechin w/w/w ratio is in the range of 1-2:1-2:1-2, and the at least one excipient is selected from the group consisting of polymer, gum base, chelating agent, emulsifier, surfactant, humectant, solvent, antimicrobial agent, moisturizer, water, fragrance, DMSO, and combinations thereof, and wherein oxyresveratrol has a weight percentage in the range of 0.30% - 0.50% with respect to the composition, and dihydrooxyresveratrol has a weight percentage in the range of 0.20% - 0.40% with respect to the composition, and catechin has a weight percentage in the range of 0.20%) - 0.40%) with respect to the composition.
[0066] In an embodiment of the present disclosure, there is provided a composition comprising: (a) oxyresveratrol; (b) dihydrooxyresveratrol; (c) catechin; and (d) at least one excipient, wherein oxyresveratrol, dihydrooxyresveratrol, and catechin w/w/w ratio is 1.33:1:1, and the at least one excipient is selected from the group consisting of polymer, gum base, chelating agent, emulsifier, surfactant, humectant, solvent, antimicrobial agent, moisturizer, water, fragrance, DMSO, and combinations thereof, and wherein oxyresveratrol has a weight percentage in the range of 0.30% - 0.50% with respect to the composition, and dihydrooxyresveratrol has a weight percentage in the range of 0.20% - 0.40% with respect to the composition, and catechin has a weight percentage in the range of 0.20%) - 0.40%) with respect to the composition.
[0067] In an embodiment of the present disclosure, there is provided a composition comprising: (a) oxyresveratrol having a weight percentage in the range of 0.30%> -0.50%) with respect to the composition; (b) dihydrooxyresveratrol having a weight percentage in the range of 0.20% - 0.40% with respect to the composition; (c) catechin having weight percentage in the range of 0.20% - 0.40% with respect to the composition; (d) polymers having a weight percentage in the range of 0.2 -0.5%) with respect to the composition; (e) gum base having a weight percentage in the range of 0.1 - 0.5% with respect to the composition; (f) chelating agents having a weight percentage in the range of 0.05 - 0.2% with respect to the composition; (g) emulsifiers having a weight percentage in the range of 1 - 5% with respect to the composition; (h) surfactants having a weight percentage in the range of 0.5 -3%> with respect to the composition; (i) humectants having a weight percentage in the range of 0.1 - 1% with respect to the composition; (j) solvents having a weight percentage in the range of 1 - 3% with respect to the composition; (k) antimicrobial agents having a weight percentage in the range of 0.1 - 1% with respect to the composition; (1) moisturizers having a weight percentage in the range of 2 - 3% with respect to the composition; and (m) bulking agent having a weight percentage in a range of 0.5% to 5% with respect to the composition, wherein oxyresveratrol, dihydrooxyresveratrol, and catechin w/w/w ratio is in the range of 1-2:1-2:1-2. In another embodiment of the present disclosure, oxyresveratrol,
dihydrooxyresveratrol, and catechin w/w/w ratio is in the range of 1-1.66:1-1.66:1-1.66. In yet another embodiment of the present disclosure, oxyresveratrol, dihydrooxyresveratrol, and catechin w/w/w ratio is 1.33:1:1.
[0068] In an embodiment of the present disclosure, there is provided a composition comprising: (a) oxyresveratrol having a weight percentage in the range of 0.35% -0.54% with respect to the composition; (b) dihydrooxyresveratrol having a weight percentage in the range of 0.25% - 0.35% with respect to the composition; (c) catechin having weight percentage in the range of 0.25% - 0.35% with respect to the composition; (d) polymers having a weight percentage in the range of 0.3 -0.4%) with respect to the composition; (e) gum base having a weight percentage in the range of 0.2 - 0.4% with respect to the composition; (f) chelating agents having a weight percentage in the range of 0.1 - 0.15% with respect to the composition; (g) emulsifiers having a weight percentage in the range of 2 - 4% with respect to the composition; (h) surfactants having a weight percentage in the range of 1 -2.5%) with respect to the composition; (i) humectants having a weight percentage in the range of 0.3 - 0.7% with respect to the composition; (j) solvents having a weight percentage in the range of 1.5 - 2.5% with respect to the composition; (k) antimicrobial agents having a weight percentage in the range of 0.3 - 0.7% with respect to the composition; and (1) moisturizers having a weight percentage in the range of 2.3 - 2.7% with respect to the composition, wherein oxyresveratrol, dihydrooxyresveratrol, and catechin w/w/w ratio is in the range of 1-2:1-2:1-2. In another embodiment of the present disclosure, oxyresveratrol, dihydrooxyresveratrol, and catechin w/w/w ratio is in the range of 1-1.66:1-1.66:1-1.66. In yet another embodiment of the present disclosure, oxyresveratrol, dihydrooxyresveratrol, and catechin w/w/w ratio is 1.33:1:1.
[0069] In an embodiment of the present disclosure, there is provided a composition comprising: (a) oxyresveratrol having a weight percentage in the range of 0.35% -0.54%) with respect to the composition; (b) dihydrooxyresveratrol having a weight percentage in the range of 0.25% - 0.35% with respect to the composition; (c) catechin having weight percentage in the range of 0.25% - 0.35% with respect to the composition; (d) polymers having a weight percentage in the range of 0.3 -
0.4% with respect to the composition, and is selected from the group consisting of ammonium acryloyl - dimethyltaurate, C10-30 alkyl acrylate crosspolymer, sodium acryloyldimethyl taurate copolymer (and) isohexadecane (and) polysorbate 60, pectin, and combinations thereof; (e) gum base having a weight percentage in the range of 0.2 - 0.4% with respect to the composition, and is selected from the group consisting of xanthan gum, guar gum, and combinations thereof; (f) chelating agents having a weight percentage in the range of 0.1 - 0.15% with respect to the composition, and is selected from the group consisting of disodium EDTA, tetrasodium EDTA, sodium phosphate, calcium disodium EDTA, and combinations thereof; (g) emulsifiers having a weight percentage in the range of 2 - 4% with respect to the composition, and is selected from the group consisting of potassium cetyl phosphate (and) hydrogenated palm glycerides, cetostearyl alcohol, magnesium isodecylbenzenesulfonate, glyceryl stearate (and) PEG-100 stearate, polysorbates, laureth-4, and potassium cetyl sulfate, and combinations thereof; (h) surfactants having a weight percentage in the range of 1 - 2.5% with respect to the composition, and is selected from the group consisting of triethanolamine, coconut oil, sodium laureth sulfate, and combinations thereof; (i) humectants having a weight percentage in the range of 0.3 - 0.7% with respect to the composition, and is selected from the group consisting of ethylhexyl glycerin, propylene glycol, glycerine, sorbitol, and combinations thereof; (j) solvents having a weight percentage in the range of 1.5 - 2.5% with respect to the composition, and is selected from the group consisting of propylene carbonate, stearate oil, mineral oil, and combinations thereof; (k) antimicrobial agents having a weight percentage in the range of 0.3 - 0.7% with respect to the composition, and is selected from the group consisting of phenoxyethanol, parabens, and combinations thereof; (1) moisturizers having a weight percentage in the range of 2.3 - 2.7% with respect to the composition, and is selected from the group consisting of C12-15 alkyl benzoate, hyaluronic acid, essential oils, and combinations thereof; and (m) bulking agent having a weight percentage in the range of 0.5-5% with respect to the composition, and is selected from the group consisting of magnesium sulfate, magnesium myristate, zinc oxide, silica, and combinations thereof, wherein oxyresveratrol,
dihydrooxyresveratrol, and catechin w/w/w ratio is in the range of 1-2:1-2:1-2. In another embodiment of the present disclosure, oxyresveratrol, dihydrooxyresveratrol, and catechin w/w/w ratio is in the range of 1-1.66:1-1.66:1-1.66. In yet another embodiment of the present disclosure, oxyresveratrol, dihydrooxyresveratrol, and catechin w/w/w ratio is 1.33:1:1.
[0070] In an embodiment of the present disclosure, there is provided a composition comprising: (a) oxyresveratrol having a weight percentage of 0.40% with respect to the composition; (b) dihydrooxyresveratrol having a weight percentage of 0.30% with respect to the composition; (c) catechin having weight percentage of 0.30% with respect to the composition; (d) ammonium acryloyl - dimethyltaurate having a weight percentage of 0.05% with respect to the composition; (e) C10-30 alkyl acrylate crosspolymer having a weight percentage of 0.17% with respect to the composition; (f) xanthan gum having a weight percentage of 0.10% with respect to the composition; (g) disodium EDTA having a weight percentage of 0.10% with respect to the composition; (h) magnesium sulfate having a weight percentage of 0.70%) with respect to the composition; (i) C12-15 alkyl benzoate having a weight percentage of 3% with respect to the composition; (j) potassium cetyl phosphate (and) hydrogenated palm glycerides having a weight percentage of 2% with respect to the composition; (k) cetostearyl alcohol having a weight percentage of 1.50% with respect to the composition; (1) glyceryl stearate (and) PEG-100 Stearate having a weight percentage of 2% with respect to the composition; (m) triethanolamine having a weight percentage of 0.2% with respect to the composition; (n) sodium acryloyldimethyl taurate copolymer (and) isohexadecane (and) polysorbate 60 having a weight percentage of 3% with respect to the composition; (o) phenoxyethanol having a weight percentage of 0.6% with respect to the composition; (p) ethylhexyl glycerin having a weight percentage of 0.5% with respect to the composition; and (q) fragrance having a weight percentage of 0.8%) with respect to the composition, wherein oxyresveratrol, dihydrooxyresveratrol, and catechin w/w/w ratio is in the range of 1-2:1-2:1-2. In another embodiment of the present disclosure, oxyresveratrol, dihydrooxyresveratrol, and catechin w/w/w ratio is 1.33:1:1.
[0071] In an embodiment of the present disclosure, there is provided a process for preparing the composition comprising: (a) oxyresveratrol; (b) dihydrooxyresveratrol; and (c) catechin, wherein oxyresveratrol, dihydrooxyresveratrol, and catechin w/w/w ratio is in the range of 1-2:1-2:1-2, said process comprising: (i) obtaining oxyresveratrol; (ii) obtaining dihydrooxyresveratrol; (iii) obtaining catechin; and (iv) contacting oxyresveratrol, dihydrooxyresveratrol, and catechin to obtain the composition. [0072] In an embodiment of the present disclosure, there is provided a process for preparing the composition comprising: (a) oxyresveratrol; (b) dihydrooxyresveratrol; and (c) catechin, wherein oxyresveratrol, dihydrooxyresveratrol, and catechin w/w/w ratio is 1.33:1:1, said process comprising: (i) obtaining oxyresveratrol; (ii) obtaining dihydrooxyresveratrol; (iii) obtaining catechin; and (iv) contacting oxyresveratrol, dihydrooxyresveratrol, and catechin to obtain the composition.
[0073] In an embodiment of the present disclosure, there is provided a process for preparing the composition comprising: (a) oxyresveratrol; (b) dihydrooxyresveratrol; and (c) catechin, wherein oxyresveratrol, dihydrooxyresveratrol, and catechin w/w/w ratio is in the range of 1-2:1-2:1-2, said process comprising: (i) obtaining oxyresveratrol; (ii) obtaining dihydrooxyresveratrol; (iii) obtaining catechin; and (iv) contacting oxyresveratrol, dihydrooxyresveratrol, and catechin to obtain the composition, wherein oxyresveratrol has a weight percentage in the range of 0.30% - 0.50% with respect to the composition. In another embodiment of the present disclosure, oxyresveratrol has a weight percentage in the range of 0.35% - 0.45% with respect to the composition. In yet another embodiment of the present disclosure, oxyresveratrol has a weight percentage in the range of 0.38% - 0.42% with respect to the composition.
[0074] In an embodiment of the present disclosure, there is provided a process for preparing the composition comprising: (a) oxyresveratrol; (b) dihydrooxyresveratrol; and (c) catechin, wherein oxyresveratrol, dihydrooxyresveratrol, and catechin w/w/w ratio is in the range of 1-2:1-2:1-2, said
process comprising: (i) obtaining oxyresveratrol; (ii) obtaining dihydrooxyresveratrol; (iii) obtaining catechin; and (iv) contacting oxyresveratrol, dihydrooxyresveratrol, and catechin to obtain the composition, wherein dihydrooxyresveratrol has a weight percentage in the range of 0.20% - 0.40% with respect to the composition. In another embodiment of the present disclosure, dihydrooxyresveratrol has a weight percentage in the range of 0.25% - 0.35% with respect to the composition. In yet another embodiment of the present disclosure, dihydrooxyresveratrol has a weight percentage in the range of 0.28% - 0.32% with respect to the composition.
[0075] In an embodiment of the present disclosure, there is provided a process for preparing the composition comprising: (a) oxyresveratrol; (b) dihydrooxyresveratrol; and (c) catechin, wherein oxyresveratrol, dihydrooxyresveratrol, and catechin w/w/w ratio is in the range of 1-2:1-2:1-2, said process comprising: (i) obtaining oxyresveratrol; (ii) obtaining dihydrooxyresveratrol; (iii) obtaining catechin; and (iv) contacting oxyresveratrol, dihydrooxyresveratrol, and catechin to obtain the composition, wherein catechin has a weight percentage in the range of 0.20% - 0.40% with respect to the composition. In another embodiment of the present disclosure, catechin has a weight percentage in the range of 0.25% - 0.35% with respect to the composition. In yet another embodiment of the present disclosure, catechin has a weight percentage in the range of 0.28% - 0.32% with respect to the composition. [0076] In an embodiment of the present disclosure, there is provided a process for preparing the composition comprising: (a) oxyresveratrol; (b) dihydrooxyresveratrol; and (c) catechin, wherein oxyresveratrol, dihydrooxyresveratrol, and catechin w/w/w ratio is in the range of 1-2:1-2:1-2, said process comprising: (i) obtaining oxyresveratrol; (ii) obtaining dihydrooxyresveratrol; (iii) obtaining catechin; and (iv) contacting oxyresveratrol, dihydrooxyresveratrol, and catechin to obtain the composition, wherein oxyresveratrol has a weight percentage in the range of 0.30% - 0.50% with respect to the composition, and dihydrooxyresveratrol has a weight percentage in the range
of 0.20% - 0.40% with respect to the composition, and catechin has a weight percentage in the range of 0.20% - 0.40% with respect to the composition. [0077] In an embodiment of the present disclosure, there is provided a process for preparing the composition comprising: (a) oxyresveratrol; (b) dihydrooxyresveratrol; (c) catechin; and (d) at least one excipient, wherein oxyresveratrol, dihydrooxyresveratrol, and catechin w/w/w ratio is in the range of 1-2:1-2:1-2, said process comprising: (i) obtaining oxyresveratrol; (ii) obtaining dihydrooxyresveratrol; (iii) obtaining catechin; (iv) obtaining the at least one excipient; and (v) contacting oxyresveratrol, dihydrooxyresveratrol, catechin and the at least one excipient, to obtain the composition, wherein the at least one excipient is selected from the group consisting of polymer, gum base, chelating agent, emulsifier, surfactant, humectant, solvent, antimicrobial agent, moisturizer, bulking agent, DMSO, and combinations thereof.
[0078] In an embodiment of the present disclosure, there is provided a process for preparing the composition comprising: (a) oxyresveratrol; (b) dihydrooxyresveratrol; (c) catechin; and (d) at least one excipient, wherein oxyresveratrol, dihydrooxyresveratrol, and catechin w/w/w ratio is 1.33:1:1, said process comprising: (i) obtaining oxyresveratrol; (ii) obtaining dihydrooxyresveratrol; (iii) obtaining catechin; (iv) obtaining the at least one excipient; and (v) contacting oxyresveratrol, dihydrooxyresveratrol, catechin and the at least one excipient, to obtain the composition, wherein the at least one excipient is selected from the group consisting of polymer, gum base, chelating agent, emulsifier, surfactant, humectant, solvent, antimicrobial agents, moisturizers, bulking agent, DMSO, and combinations thereof. [0079] In an embodiment of the present disclosure, there is provided a process for preparing the composition comprising: (a) oxyresveratrol; (b) dihydrooxyresveratrol; (c) catechin; and (d) at least one excipient, wherein oxyresveratrol, dihydrooxyresveratrol, and catechin w/w/w ratio is in the range of 1-2:1-2:1-2, said process comprising: (i) obtaining oxyresveratrol; (ii) obtaining dihydrooxyresveratrol; (iii) obtaining catechin; (iv) obtaining the at least one excipient; and (v) contacting oxyresveratrol, dihydrooxyresveratrol, catechin and
the at least one excipient, to obtain the composition, wherein the at least one excipient is selected from the group consisting of polymer, gum base, chelating agent, emulsifier, surfactant, humectant, solvent, antimicrobial agent, moisturizer, bulking agent, DMSO, and combinations thereof, and oxyresveratrol has a weight percentage in the range of 0.30% - 0.50% with respect to the composition. [0080] In an embodiment of the present disclosure, there is provided a process for preparing the composition comprising: (a) oxyresveratrol; (b) dihydrooxyresveratrol; (c) catechin; and (d) at least one excipient, wherein oxyresveratrol, dihydrooxyresveratrol, and catechin w/w/w ratio is in the range of 1-2:1-2:1-2, said process comprising: (i) obtaining oxyresveratrol; (ii) obtaining dihydrooxyresveratrol; (iii) obtaining catechin; (iv) obtaining the at least one excipient; and (v) contacting oxyresveratrol, dihydrooxyresveratrol, catechin and the at least one excipient, to obtain the composition, wherein the at least one excipient is selected from the group consisting of polymer, gum base, chelating agent, emulsifier, surfactant, humectant, solvent, antimicrobial agent, moisturizer, bulking agent, DMSO, and combinations thereof, and dihydrooxyresveratrol has a weight percentage in the range of 0.20% - 0.40% with respect to the composition. [0081] In an embodiment of the present disclosure, there is provided a process for preparing the composition comprising: (a) oxyresveratrol; (b) dihydrooxyresveratrol; (c) catechin; and (d) at least one excipient, wherein oxyresveratrol, dihydrooxyresveratrol, and catechin w/w/w ratio is in the range of 1-2:1-2:1-2, said process comprising: (i) obtaining oxyresveratrol; (ii) obtaining dihydrooxyresveratrol; (iii) obtaining catechin; (iv) obtaining the at least one excipient; and (v) contacting oxyresveratrol, dihydrooxyresveratrol, catechin and the at least one excipient, to obtain the composition, wherein the at least one excipient is selected from the group consisting of polymer, gum base, chelating agent, emulsifier, surfactant, humectant, solvent, antimicrobial agent, moisturizers, bulking agent, DMSO, and combinations thereof, and wherein catechin has a weight percentage in the range of 0.20% - 0.40% with respect to the composition. [0082] In an embodiment of the present disclosure, there is provided a process for preparing the composition comprising: (a) oxyresveratrol; (b)
dihydrooxyresveratrol; (c) catechin; and (d) at least one excipient, wherein
oxyresveratrol, dihydrooxyresveratrol, and catechin w/w/w ratio is in the range of
1-2:1-2:1-2, said process comprising: (i) obtaining oxyresveratrol; (ii) obtaining
dihydrooxyresveratrol; (iii) obtaining catechin; (iv) obtaining the at least one
excipient; and (v) contacting oxyresveratrol, dihydrooxyresveratrol, catechin and
the at least one excipient, to obtain the composition, wherein the at least one
excipient is selected from the group consisting of polymer, gum base, chelating
agent, emulsifier, surfactant, humectant, solvent, antimicrobial agent, moisturizer,
bulking agent, water, fragrance, DMSO, and combinations thereof, and
oxyresveratrol has a weight percentage in the range of 0.30% - 0.50% with respect
to the composition, dihydrooxyresveratrol has a weight percentage in the range of
0.20%) - 0.40%o with respect to the composition, and catechin has a weight
percentage in the range of 0.20% - 0.40% with respect to the composition.
[0083] In an embodiment of the present disclosure, there is provided a composition
as described herein, wherein the composition reduces skin pigmentation.
[0084] In an embodiment of the present disclosure, there is provided a composition
as described herein, wherein the composition reduces skin ageing.
[0085] In an embodiment of the present disclosure, there is provided a composition
as described herein, wherein the composition inhibits V-type ATPase subunit El
thereby inhibiting skin pigmentation.
[0086] In an embodiment of the present disclosure, there is provided a composition
as described herein, wherein the composition inhibits basigin and annexin thereby
inhibiting skin ageing.
[0087] In an embodiment of the present disclosure, there is provided a composition
as described herein, wherein the composition is formulated in form of lotion.
[0088] In an embodiment of the present disclosure, there is provided a composition
as described herein, wherein the composition is formulated in form of gels.
[0089] In an embodiment of the present disclosure, there is provided a composition
as described herein, wherein the composition is formulated in form of serum.
[0090] In an embodiment of the present disclosure, there is provided a composition
as described herein, wherein the composition is formulated in form of cream.
[0091] In an embodiment of the present disclosure, there is provided a composition
as described herein, wherein the composition is formulated in form of oil.
[0092] Although the subject matter has been described in considerable detail with
reference to certain examples and implementations thereof, other implementations
are possible.
EXAMPLES
[0093] 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.
[0094] The following section details various examples depicting the effect of the
composition as disclosed in the present disclosure on various molecular targets that
can intervene with skin pigmentation and skin ageing. Non-working example has
also been provided to support the use of the composition of the present disclosure.
Also, an example of a formulation using the composition of the present disclosure
has been depicted herewith.
Materials and Methods:
[0095] Oxyresveratrol was procured from Sami Labs., India, Stock prepared in
dimethylsulfoxide (DMSO).
[0096] Dihydrooxyresveratrol was procured from Sami Labs., India, Stock
prepared in DMSO.
[0097] Catechin purchased from Sigma, Stock prepared in DMSO.
[0098] Mouse melanoma cells (B16) and HaCats procured from ATCC, India.
[0099] Dulbecco modified eagle medium (DMEM) media purchased from Gibco,
USA.
Experiment Protocol for proteomics study: Experimentation procedure
consists of 4 days.
[00100] Day 1: B-16 Cells were seeded in T 25- flask and incubated in 5% C02
incubator at 37 °C
[00101] Day 2: B16 cells were exposed to 10 uM Forskolin for 72 hours, the
actives were treated simultaneously with Forskolin induction. Forskolin is a
melanin stimulating agent. Forskolin is commonly used as a tool in biochemistry to
raise levels of cyclic AMP (cAMP) in the study and Forskolin activates the enzyme
adenylyl cyclase and increases intracellular levels of cAMP. cAMP is an important
second messenger necessary for the proper biological response of cells to hormones
and other extracellular signals such as melanin synthesis. Day 5: Cells were lysed
and processed for proteomics analysis as per the following protocol
Melanin inhibition Assay
[00102] Co - culture of B16 cells and HaCats was used for this study. Human
keratinocyte cells and B16 Cells were seeded in appropriate culture medium
(DMEM) in the ratio of 2:5. The co-culture cells were treated with 10 uM of
Forskolin before treating with the test compositions. Cell Culture vessels were
incubated at 37 °C with a humidified 5 % CO2 atmosphere. Cell growth and
morphology was monitored on day 1, 3 and post-seeding. After 3 days of the
treatment of test compounds, the cells were collected for the total melanin assay.
The assay was performed as mentioned in the below protocol.
Melanin Determination
[00103] The assay for melanin determination consisted of following steps:
1. Cells were co-cultured (approximately 105 cells) in micro-centrifuge tubes.
2. Cells were solubilized in 1 ml of IN NaOH / 10% DMSO for 2 hours at 80°C
3. The cells were centrifuged at 12000 g for 10 min at RT, and supernatants were transferred to fresh tubes.
4. The absorbance of the supernatants was measured at 405 nm. Melanin content was determined by the absorbance/ug of protein in a cell extract.
5. The melanin content is expressed percentage of inhibition when compared to control.
Proteomics experimental protocols:
[00104] Proteomic analysis: 30 ug of total protein of each sample (untreated Human keratinocytes cell lines treated with oxyresveratrol (4 uM) dihydrooxyresveratrol 3(uM), catechin (3 uM) and forskolin (10 micromoles solution) was subjected to in solution digestion method described later. The peptide mixtures were separated using a reverse phase column nano-high performance liquid chromatography (HPLC) using pico-frit columns (Thermo) (0.075 mm x 150 mm, CI8). 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-urn 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).
[00105] In solution digestion method: In-solution protein digestion, is a proteomics protocol, where proteins are digested in solution. 100 ug of cell protein extract was resuspended in 47 ul of 6 M urea, 50 mM ammonium bicarbonate solution. One ul of 250 mM TCEP (tris (2 carboxyethyl) phosphine) was added in solution and the sample was incubated at 37°C for 30 minutes. Further 2 ul of 625 mM iodoacetamide was added and the sample was incubated in dark at room temperature (25±2°C) for 45 minutes. Finally, in-solution digestion was carried by addition of 450 ul 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).
[00106] Nano-HPLC & Mass Spectrometry
[00107] 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. Data Analysis:
[00108] Data analysis pipeline were set to carry out the results data produced by Proteome discoverer software version 1.4. An in-house Python based tool was used, for identifying the differentially expressed proteins across and among the samples. The data were searched against the mouse sequence 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. [00109] The studies using oxyresveratrol, dihydrooxyresveratrol and catechin on mouse melanoma cells (B16 Cells) were performed using in-solution LC MS/MS approach. A total of 2032 protein were identified (oxyresveratrol at 4 micro molar (4 uM) - 731 proteins , oxyresveratrol at 10 micro molar (10 uM) - 579 proteins, dihydrooxyresveratrol at 3 micro molar (3 uM) - 702 proteins, dihydrooxyresveratrol at 10 micro molar (10 uM) - 803 proteins and catechin at 3
micro molar (10 uM) 644 proteins and combination (oxyresveratrol at 4 micro molar (4 uM) + dihydrooxyresveratrol at 3 micro molar (3 uM) + catechin at 3 micro molar (10 uM) {ODC combo))- 604) proteins were identified across all eight samples tested. A total of 2032 unique protein were identified in the above set of samples and about 182 proteins were identified common across all the samples. [00110] Quantitative proteomic data analysis was performed after global data normalization. Proteins such as heat shock protein 90- beta, HSP -70 and V-type proton ATPase, are known to play key role in maintaining skin pigmentation and Basigin and Annexin A5 are known to play key role in maintaining skin aging. All the above proteins are deregulated in the various physiological conditions directly or indirectly.
Example 1
Effect of oxyresveratrol and dihydrooxyresveratrol and catechin and their
composition on Melanin inhibition assay in co culture of B16 and HacaTs
cells.
[00111] The effect of a composition comprising 4uM oxyresveratrol, 3uM dihydrooxyresveratrol, and 3uM catechin was checked on the melanin inhibition along with the individual controls orbitrap mass analyser with proteomics method as described previously.
[00112] Referring to Figure 1, it can be observed that in presence of 4uM oxyresveratrol around 33% of melanin inhibition can be observed. In the presence of 3uM dihydrooxyresveratrol and 3uM catechin individually an inhibition of 19.48% and 18.95%> can be observed. On the other hand, in the presence of a combination of three components (4uM oxyresveratrol + 3uM dihydrooxyresveratrol + 3uM catechin) an inhibition of 66.89% melanin can be observed. It can be inferred, that although the combination is not showing a synergistic inhibition of melanin but it is potentially showing an enhanced melanin inhibitory activity. Example 2
Effect of oxyresveratrol and dihydrooxyresveratrol and catechin and their composition on HSP 90- Beta protein expression in fold changes identified using orbitrap mass analyzer based on proteomics method [00113] The effect of a composition comprising 4uM oxyresveratrol, 3uM dihydrooxyresveratrol, and 3uM catechin was checked on HSP-90 P protein expression along with the individual controls using orbitrap mass analyser with proteomics method as described previously.
[00114] Figure 2 depicts the fold change of HSP-90 P protein expression in presence of 4uM oxyresveratrol (OXY4), 3uM dihydrooxyresveratrol (D3), 3uM catechin (C3), lOuM dihydrooxyresveratrol (D10), lOuM oxyresveratrol (OXY10), and a combination of 4uM oxyresveratrol + 3uM dihydrooxyresveratrol + 3uM catechin (ODC). It can be appreciated that although the combination is not displaying a synergistic decrease in expression of HSP-90 P protein expression but an enhanced effect in downregulation in presence of the combination can be observed. The results indicate that the oxyresveratrol, dihydrooxyresveratrol and catechin composition potentially decrease the HSP-90 p expression in B16 Mouse melanoma cells. HSP 90- p is a constitutively expressed heat shock protein in the endoplasmic reticulum whose expression is further up-regulated upon ultraviolet irradiation. A recent study suggested that HSP-90 P is a constituent of melanosomes (Basrur et al., Proteome Res. 2003 Jan-Feb;2(l):69-79). HSP-90 p is essential for melanin synthesis and that its function is critical to the normal distribution of tyrosinase to late melanosomes. Therefore, the composition assists in down-regulation of skin pigmentation.
Example 3
Effect of oxyresveratrol and dihydrooxyresveratrol and catechin and their
composition on HSP 70 protein expression
[00115] The effect of a composition comprising 4uM oxyresveratrol, 3uM
dihydrooxyresveratrol, and 3uM catechin was checked on HSP-70 protein
expression along with the individual controls using orbitrap mass analyser with
proteomics method as described previously.
[00116] Figure 3 depicts the fold change of HSP-70 protein expression in presence of 4uM oxyresveratrol (OXY4), 3uM dihydrooxyresveratrol (D3), 3uM catechin (C3), lOuM dihydrooxyresveratrol (D10), lOuM oxyresveratrol (OXY10), and a combination of 4uM oxyresveratrol + 3uM dihydrooxyresveratrol + 3uM catechin (ODC). It can be appreciated that although the combination is not displaying a synergistic decrease in expression of HSP-70 protein expression but an enhanced effect in downregulation in presence of the combination can be observed. The results indicate that the oxyresveratrol, dihydrooxyresveratrol and catechin composition potentially decrease the HSP-70 expression in B16 Mouse melanoma cells. Epidermal Hsp70 contributes to the diversity of skin color by regulating the amount of melanin synthesized in melanocytes and modulating autophagic melanosome degradation in keratinocytes. Thus, the present combination plays a role in decreasing skin pigmentation.
Example 4
Effect of oxyresveratrol and dihydrooxyresveratrol and catechin and their composition on V-type proton ATase subunit El protein expression [00117] The effect of a composition comprising 4uM oxyresveratrol, 3uM dihydrooxyresveratrol, and 3uM catechin was checked on V-type proton ATase subunit El protein expression along with the individual controls using orbitrap mass analyser with proteomics method as described previously. [00118] Figure 4 depicts the fold change of V-type proton ATPase subunit El protein expression in presence of 4uM oxyresveratrol (OXY4), 3uM dihydrooxyresveratrol (D3), 3uM catechin (C3), lOuM dihydrooxyresveratrol (D10), lOuM oxyresveratrol (OXY10), and a combination of 4uM oxyresveratrol + 3uM dihydrooxyresveratrol + 3uM catechin (ODC). It can be analysed that in the presence of 4uM oxyresveratrol no significant decrease in fold change of the protein was observed, in the presence of 3uM dihydrooxyresveratrol only 0.47-fold decrease in protein expression can be observed and in the presence of 3uM catechin no significant change in the protein expression can be observed. Surprisingly, in the presence of a composition comprising a combination of 4uM
oxyresveratrol + 3uM dihydrooxyresveratrol + 3uM catechin (ODC), 1.34-fold decrease in expression of the protein can be observed. It can be appreciated that the fold change in presence of the above-mentioned composition is more than the mere additive inhibition values in the presence of the three components in isolation. Therefore, a synergistic decrease in protein expression can be observed in presence of the composition as compared to the individual components. [00119] The melanosome, an organelle specialized for melanin synthesis, is one of the lysosome-related organelles. Its lumen is reported to be acidified by vacuolar-type H (+)-ATPase (V-ATPase). Melanosomal pH controls rate of melanogenesis, eumelanin/phaeomelanin ratio and melanosome maturation in melanocytes and melanoma cells. Thus, the present composition has the ability to display a decrease in pigmentation of skin.
Example 5
Effect of oxyresveratrol and dihydrooxyresveratrol and catechin and their
composition on basigin (CD147) protein expression
[00120] The effect of a composition comprising 4uM oxyresveratrol, 3uM
dihydrooxyresveratrol, and 3uM catechin was checked on basigin (CD 147) protein
expression along with the individual controls using orbitrap mass analyser with
proteomics method as described previously.
[00121] Figure 5 depicts the fold change of basigin (CD147) protein expression in
presence of 4uM oxyresveratrol (OXY4), 3uM dihydrooxyresveratrol (D3), 3uM
catechin (C3), lOuM dihydrooxyresveratrol (D10), lOuM oxyresveratrol (OXY10),
and a combination of 4uM oxyresveratrol + 3uM dihydrooxyresveratrol + 3uM
catechin (ODC). It can be analysed from Figure 5 that in the presence of 4uM
oxyresveratrol (OXY4), 3uM dihydrooxyresveratrol (D3), and 3uM catechin (C3)
in isolation, no significant decrease in fold expression of the protein is observed.
On the other hand, in the presence of the combination (ODC), a synergistic
decrease in the fold expression of the protein can be observed (3.04-fold).
[00122] Basigin, also called CD147 or EMMPRJN, is a transmembrane
glycoprotein that belongs to the immunoglobulin superfamily. Basigin, also
referred to in the art as extracellular matrix metalloproteinase inducer ("EMMPRIN"). Agents targeting basigin activity showed significant anti-inflammatory effects in experimental models, suggesting basigin interactions may be a good target for new anti-inflammatory therapeutics. Therefore, the present composition can have an anti-inflammatory effect on the skin and thus provide ant-ageing effect.
Example 6
Effect of oxyresveratrol and dihydrooxyresveratrol and catechin and their composition on Annexin A5 expression in fold changes
[00123] The effect of a composition comprising 4uM oxyresveratrol, 3uM dihydrooxyresveratrol, and 3uM catechin was checked on basigin (CD 147) protein expression along with the individual controls using orbitrap mass analyser with proteomics method as described previously.
[00124] Figure 6 depicts the fold change of annexin A5 protein expression in presence of 4uM oxyresveratrol (OXY4), 3uM dihydrooxyresveratrol (D3), 3uM catechin (C3), lOuM dihydrooxyresveratrol (D10), lOuM oxyresveratrol (OXY10), and a combination of 4uM oxyresveratrol + 3uM dihydrooxyresveratrol + 3uM catechin (ODC). It can be analysed from Figure 6 that in the presence of 4uM oxyresveratrol (OXY4), 3uM dihydrooxyresveratrol (D3), and 3uM catechin (C3) in isolation, no significant decrease in fold expression of the protein is observed. On the other hand, in the presence of the combination, a synergistic decrease in the fold expression of the protein can be observed (0.85-fold).
[00125] Annexin A5 has gained broad attention over the last decade because of its use as a molecular Imaging agent. Understanding the (patho) physiological significance of extracellular annexin A5 is of great importance in the light of these developments. Annexin A5 can play various roles in apoptosis, haemostasis and thrombosis, inflammation and immunology by shielding PS surfaces, inhibiting MPs formation and down-regulating cell surface-expression of receptors. Thus, the present composition help in rendering anti-inflammatory activity by targeting the molecular system of the cell.
Example 7
Effect of oxyresveratrol and 6'7'4-Trihydro isoflavone and catechin and their composition on melanin inhibition activity
[00126] The present example is intended to study the effect of a composition comprising a combination of 4uM oxyresveratrol + 3uM 6'7'4-Trihydro isoflavone + 3uM catechin on melanin inhibition activity.
[00127] Figure 7 depicts the effect of the following compositions: (a) 10 uM oxyresveratrol; (b) 5 uM oxyresveratrol + 5uM catechin; (c) 5uM catechin + 5uM 6'7'4-Trihydro isoflavone; (d) 5 uM dihydrooxyresveratrol + 5uM catechin; and (e) 4uM oxyresveratrol + 3uM 6'7'4-Trihydro isoflavone + 3uM catechin on melanin inhibition. It can be analysed from Figure 7, that the compositions (a), (b), (d), and (e) display around 60-61% of melanin inhibition. The composition (e) comprising 4uM oxyresveratrol + 3uM 6'7'4-Trihydro isoflavone + 3uM catechin does not display any significant increase nor does it display a synergistic increase over other compositions. Thus, it can be inferred that the composition of the present disclosure (oxyresveratrol, dihydrooxyresveratrol, catechin) is arrived upon after significant experimentation and replacing a single component with another one does not display the desirable result.
Example 8
A Formulation comprising the composition of the present disclosure [00128] The present example depicts a formulation comprising the combination of oxyresveratrol, dihydrooxyresveratrol, and catechin. The formulation as depicted in Table 1 is only one of such formulations that can be made using the present composition. It can be contemplated that many such formulations are possible depending on the type of excipients and additives being added in the formulation. Table 1: Formulation comprising the present composition
[00129] Process for preparation of the formulation: The formulation as disclosed herein was prepared by adding all the excipients and the actives (catechin, oxyresveratrol and dihydrooxyresveratrol) and mixing them properly under ambient conditions.
[00130] It can be contemplated that the formulation can be prepared by adding all the components in the disclosed weight percentages. The order of adding the components can be varied as per the process followed.
[00131] Overall, it can be summarised that Examples 1-4 depict the role of the present composition in decreasing skin pigmentation by targeting the melanogenesis system of the cell. Although, no synergistic effect was observed in the inhibition of melanin inhibition, HSP-90 down-regulation, and HSP-70 down-regulation but enhanced effect was observed which play a role in decreasing skin pigmentation. On the other hand, synergistic effect was observed in decreasing the expression of V-type proton ATPase subunit El which play a role in melanogenesis. Thus, considering the overall effect on controlling the melanogenesis rate, the present composition targets multiple molecular system. Examples 5 and 6 depict the effect of the present composition in synergistically decreasing the fold expression of basigin and annexin protein. Since, both the proteins are known to play a role in inflammation and skin ageing, the composition as disclosed in the present disclosure also plays a role in reducing skin inflammation and skin ageing apart from reducing skin pigmentation. Example 7 provides a non-working example in which a component was replaced with another component. Example 8 provides one example of a formulation that can be arrived upon by using the composition of the present disclosure.
[00132] Although, the effect of composition comprising oxyresveratrol, dihydrooxyresveratrol, catechin in a weight ratio of 1.33:1:1 has been depicted by means of various examples, but it can be contemplated that other possible combinations within a range of weight ratio 1-2:1-2:1-2 of oxyresveratrol, dihydrooxyresveratrol, and catechin shall display similar beneficial effects. Advantages of the present disclosure
[00133] The composition of the present disclosure comprises a combination of oxyresveratrol, dihydrooxyresveratrol, and catechin. Specifically, it comprises a combination of 4uM oxyresveratrol, 3uM dihydrooxyresveratrol, and 3uM catechin. The composition intervenes with multiple targets to reduce skin pigmentation, inflammation, and decrease skin ageing. Therefore, the present composition is beneficial to the skin in multiple ways and ensures the maintenance of overall health of the skin. Thus, it can be considered as a single solution to multiple skin related problems.
I/We Claim:
1. A composition comprising:
a) oxyresveratrol;
b) dihydrooxyresveratrol; and
c) catechin,
wherein oxyresveratrol, dihydrooxyresveratrol, and catechin w/w/w ratio is in the range of 1-2:1-2:1-2.
2. The composition as claimed in claim 1, wherein oxyresveratrol, dihydrooxyresveratrol, and catechin w/w/w ratio is 1.33:1:1.
3. The composition as claimed in claim 1, wherein oxyresveratrol has a weight percentage in the range of 0.30% - 0.50% with respect to the composition.
4. The composition as claimed in claim 1, wherein dihydrooxyresveratrol has
a weight percentage in the range of 0.20% - 0.40% with respect to the
composition.
5. The composition as claimed in claim 1, wherein catechin has a weight percentage in the range of 0.20% - 0.40% with respect to the composition.
6. The composition as claimed in claim 1, wherein the composition further comprises at least one excipient selected from the group consisting of polymer, gum base, chelating agent, emulsifier, surfactant, humectant, solvent, antimicrobial agent, moisturizer, water, fragrance, dimethyl sulfoxide (DMSO), bulking agent, and combinations thereof.
7. The composition as claimed in any of the claims 1-6, wherein the composition reduces skin pigmentation.
8. The composition as claimed in any of the claims 1-6, wherein the composition reduces skin ageing.
9. A process for preparing the composition as claimed in any of the claims 1-5, said process comprising:
a) obtaining oxyresveratrol;
b) obtaining dihydrooxyresveratrol;
c) obtaining catechin; and
d) contacting oxyresveratrol, dihydrooxyresveratrol, and catechin to obtain the composition. 10. A process for preparing the composition as claimed in claim 6, said process comprising:
a) obtaining oxyresveratrol;
b) obtaining dihydrooxyresveratrol;
c) obtaining catechin;
d) obtaining the at least one excipient; and
e) contacting oxyresveratrol, dihydrooxyresveratrol, catechin, and the at least one excipient to obtain the composition.
| # | Name | Date |
|---|---|---|
| 1 | 201841012151-STATEMENT OF UNDERTAKING (FORM 3) [30-03-2018(online)].pdf | 2018-03-30 |
| 2 | 201841012151-FORM 1 [30-03-2018(online)].pdf | 2018-03-30 |
| 3 | 201841012151-DRAWINGS [30-03-2018(online)].pdf | 2018-03-30 |
| 4 | 201841012151-DECLARATION OF INVENTORSHIP (FORM 5) [30-03-2018(online)].pdf | 2018-03-30 |
| 5 | 201841012151-COMPLETE SPECIFICATION [30-03-2018(online)].pdf | 2018-03-30 |
| 6 | 201841012151-Proof of Right (MANDATORY) [08-05-2018(online)].pdf | 2018-05-08 |
| 7 | 201841012151-FORM-26 [08-05-2018(online)].pdf | 2018-05-08 |
| 8 | Correspondence by Agent_Form1, Power of Attorney_10-05-2018.pdf | 2018-05-10 |
| 9 | 201841012151-FORM 18 [17-12-2021(online)].pdf | 2021-12-17 |
| 10 | 201841012151-FER.pdf | 2022-02-02 |
| 11 | 201841012151-FER_SER_REPLY [02-08-2022(online)].pdf | 2022-08-02 |
| 12 | 201841012151-PatentCertificate23-11-2023.pdf | 2023-11-23 |
| 13 | 201841012151-IntimationOfGrant23-11-2023.pdf | 2023-11-23 |
| 1 | search02022022E_02-02-2022.pdf |