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A Composition To Reduce Skin Pigmentation

Abstract: The present disclosure relates to a composition comprising dihydrooxyresveratrol and glycyrrhizic acid which at specific ratios and concentrations can be used for the treatment of skin problems such as skin aging and skin pigmentation. Also provided are methods of preparation and uses of the said composition.

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Patent Information

Application #
Filing Date
29 March 2017
Publication Number
40/2018
Publication Type
INA
Invention Field
CHEMICAL
Status
Email
iprdel@lakshmisri.com
Parent Application
Patent Number
Legal Status
Grant Date
2022-06-29
Renewal Date

Applicants

ITC LIMITED
ITC LIFE SCIENCES & TECHNOLOGY CENTRE #3. 1st Main, Peenya Industrial Area, Phase-1, Bangalore 560 058, India

Inventors

1. MUTHAIYAH, Balu
ITC LIFE SCIENCES & TECHNOLOGY CENTRE #3. 1st Main, Peenya Industrial Area, Phase-1, Bangalore 560 058, India
2. BANDYOPADHYAY, Balaji
ITC LIFE SCIENCES & TECHNOLOGY CENTRE #3. 1st Main, Peenya Industrial Area, Phase-1, Bangalore 560 058, India
3. CHANDRASEKHARAN, Lakshmanan Chittur
ITC LIFE SCIENCES & TECHNOLOGY CENTRE #3. 1st Main, Peenya Industrial Area, Phase-1, Bangalore 560 058, India

Specification

FIELD OF THE INVENTION
[001] The present disclosure relates to the field of cosmetic formulations in general and compositions for the inhibition of skin pigmentation in particular. There is provided a composition to address the problem of skin pigmentation.
BACKGROUND OF THE INVENTION
[002] Skin pigmentation has been of concern to human beings for ages. In
particular, a uniform complexion free from hyperpigmentation, such as age spots,
freckles or aging skin is the desire of individuals.
[003] Skin colour is primarily determined by the amount and type of melanin
present in the skin. Melanin’s compose a class of compounds that serve
predominantly as a pigment. These pigments are derivatives of the amino acid
tyrosine. There are at least three types of naturally occurring melanins: eumelanin,
pheomelanin, and neuromelanin. Lower amounts of melanin results in lighter skin
color while higher amounts result in darker skin color.
[004] Several factors contribute to skin pigmentation. Among the major extrinsic
factors influencing skin pigmentation is the exposure to the sun for long time, which
can induce many biochemical reactions in the skin, leading to sunburn and tanning of
the skin. These changes can result in the developments of skin spots and creating an
uneven, mottled skin tone.
[005] An uneven skin tone and the pigmentation of skin is considered an undesired
cosmetic feature among people, and therefore efforts are underway to find ways to
reduce skin pigmentation. Research has focused on the agents that inhibit the activity
of melanin production. For example, a variety of tyrosinase inhibitors, such as
hydroquinone, vitamin C, cysteine, kojic acid, arbutin and glutathione among others
have been proposed in topical formulations.
[006] However, many of these formulations contain harsh chemicals such as
peroxides, acids or formaldehyde, or thiolated materials. Less stringent therapies have

other disadvantages. Topical retinoid and topical corticosteroids have been suggested as hypo-pigmenting agents, but these fall short of desirable results.
[007] It would thus be highly desirable to have alternative preparations that do not have the drawbacks of those described in the prior art.
SUMMARY OF THE INVENTION
[008] In an aspect of the present disclosure, there is provided a composition to
reduce skin pigmentation comprising: (a) dihydrooxyresveratrol; and (b) glycyrrhizic
acid and salts thereof, wherein the dihydrooxyresveratrol to the glycyrrhizic acid and
salts thereof w/w ratio in said composition is in the range of 1:2 – 1:4.
[009] In an aspect of the present disclosure, there is provided a method of preparing
a composition to reduce skin pigmentation comprising: (a) dihydrooxyresveratrol;
and (b) glycyrrhizic acid and salts thereof, wherein the dihydrooxyresveratrol to the
glycyrrhizic acid and salts thereof w/w ratio in said composition is in the range of 1:2
– 1:4, said method comprising: (i) obtaining dihydrooxyresveratrol; (ii) obtaining
glycyrrhizic acid and salts thereof; and (iii) contacting dihydrooxyresveratrol,
glycyrrhizic acid and salts thereof to obtain said composition.
[010] In an aspect of the present disclosure, there is provided a method of reducing
skin pigmentation, said method comprising: (a) obtaining a composition comprising:
(i) dihydrooxyresveratrol; and (ii) glycyrrhizic acid and salts thereof, wherein the
dihydrooxyresveratrol to the glycyrrhizic acid and salts thereof w/w ratio in said
composition is in the range of 1:2 – 1:4; and (b) contacting said composition with
skin, wherein said composition reduces skin pigmentation.
[011] 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 ACCOMPANYING DRAWINGS
[012] The following drawings form 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.
[013] Figure 1 depicts the effect of various concentrations of dihydrooxyresveratrol
on the viability of Human Adult Primary Melanocytes (HEMa), in accordance with
an embodiment of present disclosure.
[014] Figure 2 depicts the effect of various concentrations of glycyrrhizic acid on
the viability of Human Adult Primary Melanocytes (HEMa), in accordance with an
embodiment of the present disclosure.
[015] Figure 3 depicts the effects of a combination of dihydrooxyresveratrol and
glycyrrhizic acid on the inhibition of melanocytes, in accordance with an embodiment
of present disclosure.
DETAILED DESCRIPTION OF THE INVENTION
[016] 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
[017] 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.
[018] 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.
[019] 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”.
[020] 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.
[021] The term “including” is used to mean “including but not limited to”.
“Including” and “including but not limited to” are used interchangeably.
[022] Carriers are substances that serve as mechanisms to improve the delivery and
the effectiveness of drugs.
[023] A diluent (also referred to as filler, dilutant, or thinner) is a diluting agent.
[024] An excipient is an inactive substance that serve as the vehicle or medium for a
drug or other active substance. Excipients include colouring agents, humectants,
preservatives, emollients, and combinations thereof.
[025] 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.
[026] Skin pigmentation is one of the prime concerns of the people nowadays. Skin
lightening compositions have been widely expanded but unfortunately many of the

commercially available products in today’s market are either only marginally effective, or contain active agents that are unstable and lose their potency when incorporated into a final formula. In order to combat disorders related to abnormal pigment or to lighten skin tone, various compounds which, when applied topically to the skin, are capable of reducing tyrosinase activity and consequently limiting melanin production, have thus been proposed. Unfortunately, the treatments currently available are not entirely satisfactory, in particular in terms of the side effects which are frequently associated with, such as irritant side effects with certain topical agents. It would thus be highly desirable to have alternative preparations that do not have the drawbacks of those described in the prior art. In particular, it would be highly desirable to develop cosmetic compositions to be administered via topical that have improved stability and efficacy to promote an evenness skin tone or to lighten skin tone. There also remains a need to active agents that are effective for treating and/or preventing skin pigmentation disorders, in particular those due to environmental factors or aging. The present disclosure provides herein, a composition comprising dihydrooxyresveratrol and a salt of glycyrrhizic acid that helps in preventing skin pigmentation, which overcomes the limitations of the given prior arts.
[027] 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.
[028] In an embodiment of the present disclosure, there is provided a composition to reduce skin pigmentation comprising: (a) dihydrooxyresveratrol; and (b) glycyrrhizic acid and salts thereof, wherein the dihydrooxyresveratrol to the glycyrrhizic acid and salts thereof w/w ratio in said composition is in the range of 1:2 - 1:4.
[029] In an embodiment of the present disclosure, there is provided a composition to reduce skin pigmentation comprising: (a) dihydrooxyresveratrol; and (b) glycyrrhizic acid and salts thereof, wherein the dihydrooxyresveratrol to the glycyrrhizic acid and salts thereof w/w ratio in said composition is 1:3.2.

[030] In an embodiment of the present disclosure, there is provided a composition to reduce skin pigmentation comprising: (a) dihydrooxyresveratrol; and (b) glycyrrhizic acid and salts thereof, wherein said glycyrrhizic acid salts comprise organic salts and inorganic salts, and the dihydrooxyresveratrol to the glycyrrhizic acid and salts thereof w/w ratio in said composition is in the range of 1:2- 1:4.
[031] In an embodiment of the present disclosure, there is provided a composition to reduce skin pigmentation comprising: (a) dihydrooxyresveratrol; and (b) glycyrrhizic acid and salts thereof, wherein said glycyrrhizic acid salt comprises organic salts and inorganic salts, and the dihydrooxyresveratrol to the glycyrrhizic acid and salts thereof w/w ratio in said composition is 1:3.2.
[032] In an embodiment of the present disclosure, there is provided a composition to reduce skin pigmentation comprising: (a) dihydrooxyresveratrol; and (b) glycyrrhizic acid and salts thereof, wherein said glycyrrhizic acid salt comprises ammonium salt of glycyrrhizic acid, and the dihydrooxyresveratrol to the glycyrrhizic acid and salts thereof w/w ratio in said composition is in the range of 1:2 - 1:4.
[033] In an embodiment of the present disclosure, there is provided a composition to reduce skin pigmentation comprising: (a) dihydrooxyresveratrol; and (b) glycyrrhizic acid and salts thereof, wherein said glycyrrhizic acid salt comprises ammonium salt of glycyrrhizic acid and the dihydrooxyresveratrol to the glycyrrhizic acid and salts thereof w/w ratio in said composition is 1:3.2.
[034] In an embodiment of the present disclosure, there is provided a composition comprising: (a) dihydrooxyresveratrol having weight percentage in said composition in the range of 0.0005% - 0.0009%; and (b) glycyrrhizic acid having weight percentage in said composition in the range of 0.001%- 0.003%, wherein the dihydrooxyresveratrol to the glycyrrhizic acid and salts thereof w/w ratio in said composition is in the range of 1:2 - 1:4.
[035] In an embodiment of the present disclosure, there is provided a composition comprising: (a) dihydrooxyresveratrol having weight percentage in said composition of 0.000615%; and (b) glycyrrhizic acid salt having weight percentage in said

composition of 0.002%, wherein the dihydrooxyresveratrol to the glycyrrhizic acid and salts thereof w/w ratio in said composition is in the range of 1:2- 1:4. [036] In an embodiment of the present disclosure, there is provided a composition comprising: (a) dihydrooxyresveratrol having weight percentage in said composition of 0.000615%; and (b) glycyrrhizic acid salt having weight percentage in said composition of 0.002%, wherein the dihydrooxyresveratrol to the glycyrrhizic acid and salts thereof w/w ratio in said composition is 1:3.2.
[037] In an embodiment of the present disclosure, there is provided a composition comprising: (a) dihydrooxyresveratrol having weight percentage in said composition in the range of 0.0005%- 0.0009%; and (b) glycyrrhizic acid salt having weight percentage in said composition in the range of 0.001% - 0.003%, wherein said glycyrrhizic acid salt is an ammonium salt and the dihydrooxyresveratrol to the glycyrrhizic acid and salts thereof w/w ratio in said composition is in the range of 1:2- 1:4.
[038] In an embodiment of the present disclosure, there is provided a composition comprising: (a) dihydrooxyresveratrol having weight percentage in said composition in the range of 0.0005% - 0.0009%; and (b) glycyrrhizic acid salt having weight percentage in said composition in the range of 0.001% - 0.003%, wherein said glycyrrhizic salt is an ammonium salt and the dihydrooxyresveratrol to the glycyrrhizic acid and salts thereof w/w ratio in said composition is 1:3.2.
[039] In an embodiment of the present disclosure, there is provided a composition comprising: (a) dihydrooxyresveratrol having weight percentage in said composition of 0.000615%; and (b) glycyrrhizic acid salt having weight percentage in said composition of 0.002%, wherein said glycyrrhizic acid salt is an ammonium salt and the dihydrooxyresveratrol to the glycyrrhizic acid and salts thereof w/w ratio in said composition is in the range of 1:2 - 1:4.
[040] In an embodiment of the present disclosure, there is provided a composition comprising: (a) dihydrooxyresveratrol having weight percentage in said composition of 0.000615%; and (b) glycyrrhizic acid salt having weight percentage in said

composition of 0.002%, wherein said glycyrrhizic acid salt is an ammonium salt and the dihydrooxyresveratrol to the glycyrrhizic acid and salts thereof w/w ratio in said composition is 1:3.2.
[041] In an embodiment of the present disclosure, there is provided a composition to reduce skin pigmentation comprising: (a) dihydrooxyresveratrol; (b) glycyrrhizic acid and salts thereof; (c) at least one carrier; (d) at least one diluent; and (e) at least one excipients, wherein the dihydrooxyresveratrol to the glycyrrhizic acid and salts thereof w/w ratio in said composition is in the range of 1:2- 1:4.
[042] In an embodiment of the present disclosure, there is provided a composition to reduce skin pigmentation comprising: (a) dihydrooxyresveratrol; (b) glycyrrhizic acid and salts thereof; (c) at least one carrier; (d) at least one diluent; and (e) at least one excipient, wherein the dihydrooxyresveratrol to the glycyrrhizic acid and salts thereof w/w ratio in said composition is 1:3.2.
[043] In an embodiment of the present disclosure, there is provided a composition to reduce skin pigmentation comprising: (a) dihydrooxyresveratrol; (b) glycyrrhizic acid and salts thereof; (c) at least one carrier; (d) at least one diluent; and (e) at least one excipient, wherein said glycyrrhizic acid salt comprises organic salts and inorganic salts, and the dihydrooxyresveratrol to the glycyrrhizic acid and salts thereof w/w ratio in said composition is in the range of 1:2- 1:4.
[044] In an embodiment of the present disclosure, there is provided a composition to reduce skin pigmentation comprising: (a) dihydrooxyresveratrol; (b) glycyrrhizic acid and salts thereof; (c) at least one carriers; (d) at least one diluent; and (e) at least one excipient, wherein said glycyrrhizic acid salt comprises organic salts and inorganic salts, and the dihydrooxyresveratrol to the glycyrrhizic acid and salts thereof w/w ratio in said composition is 1:3.2.
[045] In an embodiment of the present disclosure, there is provided a composition to reduce skin pigmentation comprising: (a) dihydrooxyresveratrol; (b) glycyrrhizic acid and salts thereof; (c) at least one carrier; (d) at least one diluent; and (e) at least one excipient, wherein said glycyrrhizic acid salt comprises an ammonium salt of

glycyrrhizic acid, and the dihydrooxyresveratrol to the glycyrrhizic acid and salts thereof w/w ratio in said composition is in the range of 1:2- 1:4.
[046] In an embodiment of the present disclosure, there is provided a composition to reduce skin pigmentation comprising: (a) dihydrooxyresveratrol; (b) glycyrrhizic acid and salts thereof, (c) at least one carrier; (d) at least one diluent; and (e) at least one excipient, wherein said glycyrrhizic acid salt comprises an ammonium salt of glycyrrhizic acid and the dihydrooxyresveratrol to the glycyrrhizic acid and salts thereof w/w ratio in said composition is 1:3.2.
[047] In an embodiment of the present disclosure, there is provided a composition comprising: (a) dihydrooxyresveratrol having weight percentage in said composition in the range of 0.0005%- 0.0009%; (b) glycyrrhizic acid salt having weight percentage in said composition in the range of 0.001%- 0.003%; (c) at least one carrier; (d) at least one diluent; and (e) at least one excipient, wherein dihydrooxyresveratrol to glycyrrhizic acid and salts thereof w/w ratio in said composition is in the range of 1:2- 1:4.
[048] In an embodiment of the present disclosure, there is provided a composition comprising: (a) dihydrooxyresveratrol having weight percentage in said composition in the range of 0.0005% - 0.0009%; (b) glycyrrhizic acid salt having weight percentage in said composition in the range of 0.001% - 0.003%; (c) at least one carrier; (d) at least one diluent; and (e) at least one excipient, wherein the dihydrooxyresveratrol to the glycyrrhizic acid and salts thereof w/w ratio in said composition is 1:3.2.
[049] In an embodiment of the present disclosure, there is provided a composition comprising: (a) dihydrooxyresveratrol having weight percentage in said composition in the range of 0.0005% - 0.0009%; (b) glycyrrhizic acid salt having weight percentage in said composition in the range of 0.001% - 0.003%; (c) at least one carrier; (d) at least one diluent; and (e) at least one excipient, wherein said glycyrrhizic acid salt is an ammonium salt and the dihydrooxyresveratrol to the

glycyrrhizic acid and salts thereof w/w ratio in said composition is in the range of 1:2 - 1:4.
[050] In an embodiment of the present disclosure, there is provided a composition comprising: (a) dihydrooxyresveratrol having weight percentage in said composition in the range of 0.0005% - 0.0009%; (b) glycyrrhizic acid salt having weight percentage in said composition in the range of 0.001% - 0.003%; (c) at least one carrier; (d) at least one diluent; and (e) at least one excipient, wherein said glycyrrhizic acid salt is an ammonium salt and the dihydrooxyresveratrol to the glycyrrhizic acid and salts thereof w/w ratio in said composition is 1:3.2.
[051] In an embodiment of the present disclosure, there is provided a method of
preparing a composition comprising: (a) obtaining dihydrooxyresveratrol; (b)
obtaining glycyrrhizic acid and salts thereof; and (c) contacting
dihydrooxyresveratrol, glycyrrhizic acid and salts thereof to obtain said composition, wherein the dihydrooxyresveratrol to the glycyrrhizic acid and salts thereof w/w ratio in said composition is in the range of 1:2 - 1:4.
[052] In an embodiment of the present disclosure, there is provided a method of
preparing a composition comprising: (a) obtaining dihydrooxyresveratrol; (b)
obtaining glycyrrhizic acid and salts thereof; and (c) contacting
dihydrooxyresveratrol, glycyrrhizic acid and salts thereof to obtain said composition, wherein said glycyrrhizic acid salts comprises organic salts and inorganic salts, and the dihydrooxyresveratrol to the glycyrrhizic acid and salts thereof w/w ratio in said composition is in the range of 1:2 - 1:4.
[053] In an embodiment of the present disclosure, there is provided a method of
preparing a composition comprising: (a) obtaining dihydrooxyresveratrol; (b)
obtaining glycyrrhizic acid and salts thereof; and (c) contacting
dihydrooxyresveratrol, glycyrrhizic acid and salts thereof to obtain said composition, wherein said glycyrrhizic acid salt is an ammonium salt of glycyrrhizic acid, and the dihydrooxyresveratrol to the glycyrrhizic acid and salts thereof w/w ratio in said composition is in the range of 1:2 - 1:4.

[054] In an embodiment of the present disclosure, there is provided a method for preparing a composition comprising: (a) obtaining dihydrooxyresveratrol having weight percentage in the range of 0.0005 % - 0.0009 % in said composition; (b) obtaining glycyrrhizic acid salt having weight percentage in the range of 0.001 % -0.003 % in said composition; and (c) contacting dihydrooxyresveratrol and glycyrrhizic acid to obtain said composition, wherein the dihydrooxyresveratrol to the glycyrrhizic acid and salts thereof w/w ratio in said composition is in the range of 1:2 - 1:4.
[055] In an embodiment of the present disclosure, there is provided a method of preparing a composition comprising: (a) obtaining dihydrooxyresveratrol having weight percentage of 0.000615 % in said composition; (b) obtaining glycyrrhizic acid salt having weight percentage of 0.002 % in said composition; and (c) contacting dihydrooxyresveratrol, glycyrrhizic acid and salts thereof to obtain said composition, wherein the dihydrooxyresveratrol to the glycyrrhizic acid and salts thereof w/w ratio in said composition is in the range of 1:2 - 1:4.
[056] In an embodiment of the present disclosure, there is provided a method for preparing a composition comprising: (a) obtaining dihydrooxyresveratrol having weight percentage in the range of 0.0005 % - 0.0009 % in said composition; (b) obtaining glycyrrhizic acid salt having weight percentage in the range of 0.001 % -0.003 % in said composition; and (c) contacting dihydrooxyresveratrol and glycyrrhizic acid to obtain said composition, wherein said glycyrrhizic salt is an ammonium salt and the dihydrooxyresveratrol to the glycyrrhizic acid and salts thereof w/w ratio in said composition is in the range of 1:2- 1:4.
[057] In an embodiment of the present disclosure, there is provided a method of preparing a composition comprising: (a) obtaining dihydrooxyresveratrol having weight percentage of 0.000615 % in said composition; (b) obtaining glycyrrhizic acid salt having weight percentage of 0.002 % in said composition; and (c) contacting dihydrooxyresveratrol, glycyrrhizic acid and salts thereof to obtain said composition, wherein said glycyrrhizic acid salt is an ammonium salt and the

dihydrooxyresveratrol to the glycyrrhizic acid and salts thereof w/w ratio in said composition is in the range of 1:2 - 1:4.
[058] In an embodiment of the present disclosure, there is provided a method of
preparing a composition comprising: (a) obtaining dihydrooxyresveratrol; (b)
obtaining glycyrrhizic acid and salts thereof; and (c) contacting
dihydrooxyresveratrol, glycyrrhizic acid and salts thereof to obtain said composition, wherein the dihydrooxyresveratrol to the glycyrrhizic acid and salts thereof w/w ratio in said composition is 1:3.2.
[059] In an embodiment of the present disclosure, there is provided a method of
preparing a composition comprising: (a) obtaining dihydrooxyresveratrol; (b)
obtaining glycyrrhizic acid and salts thereof; and (c) contacting
dihydrooxyresveratrol, glycyrrhizic acid and salts thereof to obtain said composition, wherein said glycyrrhizic acid salts comprise organic salts and inorganic salts, and the dihydrooxyresveratrol to the glycyrrhizic acid and salts thereof w/w ratio in said composition is 1:3.2.
[060] In an embodiment of the present disclosure, there is provided a method of
preparing a composition comprising: (a) obtaining dihydrooxyresveratrol; (b)
obtaining glycyrrhizic acid and salts thereof; and (c) contacting
dihydrooxyresveratrol, glycyrrhizic acid and salts thereof to obtain said composition, wherein said glycyrrhizic acid salt is an ammonium salt of glycyrrhizic acid, and the dihydrooxyresveratrol to the glycyrrhizic acid and salts thereof w/w ratio in said composition is 1:3.2.
[061] In an embodiment of the present disclosure, there is provided a method for preparing a composition comprising: (a) obtaining dihydrooxyresveratrol having weight percentage in the range of 0.0005 % - 0.0009 % in said composition; (b) obtaining glycyrrhizic acid salt having weight percentage in the range of 0.001 % -0.003 % in said composition; and (c) contacting dihydrooxyresveratrol and glycyrrhizic acid to obtain said composition, wherein the dihydrooxyresveratrol to the glycyrrhizic acid and salts thereof w/w ratio in said composition is 1:3.2.

[062] In an embodiment of the present disclosure, there is provided a method of preparing a composition comprising: (a) obtaining dihydrooxyresveratrol having weight percentage of 0.000615 % in said composition; (b) obtaining glycyrrhizic acid salt having weight percentage of 0.002 % in said composition; and (c) contacting dihydrooxyresveratrol, glycyrrhizic acid and salts thereof to obtain said composition, wherein the dihydrooxyresveratrol to the glycyrrhizic acid and salts thereof w/w ratio in said composition is 1:3.2.
[063] In an embodiment of the present disclosure, there is provided a method for preparing a composition comprising: (a) obtaining dihydrooxyresveratrol having weight percentage in the range of 0.0005 % - 0.0009 % in said composition; (b) obtaining glycyrrhizic acid salt having weight percentage in the range of 0.001 % -0.003 % in said composition; and (c) contacting dihydrooxyresveratrol and glycyrrhizic acid to obtain said composition, wherein said glycyrrhizic acid salt is an ammonium salt and the dihydrooxyresveratrol to the glycyrrhizic acid and salts thereof w/w ratio in said composition is 1:3.2.
[064] In an embodiment of the present disclosure, there is provided a method of preparing a composition comprising: (a) obtaining dihydrooxyresveratrol having weight percentage of 0.000615 % in said composition; (b) obtaining glycyrrhizic acid salt having weight percentage of 0.002 % in said composition; and (c) contacting dihydrooxyresveratrol, glycyrrhizic acid and salts thereof to obtain said composition, wherein said glycyrrhizic acid salt is an ammonium salt and the dihydrooxyresveratrol to the glycyrrhizic acid and salts thereof w/w ratio in said composition is 1:3.2.
[065] In an embodiment of the present disclosure, there is provided a method of preparing a composition comprising: (a) obtaining dihydrooxyresveratrol; (b) obtaining glycyrrhizic acid and salts thereof; (c) obtaining at least one carrier; (d) obtaining at least one diluent; (e) obtaining at least one excipient; and (f) contacting dihydrooxyresveratrol, glycyrrhizic acid and salts thereof, at least one carrier, at least one diluent, and at least one excipient to obtain said composition, wherein the

dihydrooxyresveratrol to the glycyrrhizic acid and salts thereof w/w ratio in said composition is in the range of 1:2 - 1:4.
[066] In an embodiment of the present disclosure, there is provided a method of preparing a composition comprising: (a) obtaining dihydrooxyresveratrol; (b) obtaining glycyrrhizic acid and salts thereof; (c) obtaining at least one carrier; (d) obtaining at least one diluent; and (e) obtaining at least one excipient; and (f) contacting dihydrooxyresveratrol, glycyrrhizic acid and salts thereof, at least one carrier, at least one diluent and at least one excipient to obtain said composition, wherein said glycyrrhizic acid salts comprise organic salts and inorganic salts, and the dihydrooxyresveratrol to the glycyrrhizic acid and salts thereof w/w ratio in said composition is in the range of 1:2 - 1:4.
[067] In an embodiment of the present disclosure, there is provided a method of preparing a composition comprising: (a) obtaining dihydrooxyresveratrol; (b) obtaining glycyrrhizic acid and salts thereof; (c) obtaining at least one carrier; (d) at least one diluent (e) at least one excipient; and (f) contacting dihydrooxyresveratrol, glycyrrhizic acid and salts thereof, at least one carrier, at least one diluent and at least one excipient- to obtain said composition, wherein said glycyrrhizic acid salt is an ammonium salt of glycyrrhizic acid, and the dihydrooxyresveratrol to the glycyrrhizic acid and salts thereof w/w ratio in said composition is in the range of 1:2- 1:4. [068] In an embodiment of the present disclosure, there is provided a method for preparing a composition comprising: (a) obtaining dihydrooxyresveratrol; (b) obtaining glycyrrhizic acid; (c) obtaining at least one carrier; (d) obtaining at least one diluent; (e) obtaining at least one excipient; and (f) contacting dihydrooxyresveratrol, glycyrrhizic acid, at least one carrier, at least one diluent and at least one excipients to obtain said composition, wherein dihydrooxyresveratrol weight percentage in said composition is in the range of 0.0005% - 0.0009%, glycyrrhizic acid weight percentage in said composition is in the range of 0.001% -0.003%, and the dihydrooxyresveratrol to the glycyrrhizic acid and salts thereof w/w ratio in said composition is in the range of 1:2 - 1:4.

[069] In an embodiment of the present disclosure, there is provided a method of preparing a composition comprising: (a) obtaining dihydrooxyresveratrol having weight percentage of 0.000615 %; (b) obtaining glycyrrhizic acid salt having weight percentage of 0.002 %; (c) obtaining suitable carriers, diluents, and excipients; and (f) contacting dihydrooxyresveratrol, glycyrrhizic acid and salts thereof, at least one carrier, at least one diluent and at least one excipient to obtain said composition, wherein the dihydrooxyresveratrol to the glycyrrhizic acid and salts thereof w/w ratio in said composition is in the range of 1:2 - 1:4.
[070] In an embodiment of the present disclosure, there is provided a method for preparing a composition comprising: (a) obtaining dihydrooxyresveratrol; (b) obtaining glycyrrhizic acid; (c) obtaining at least one carrier; (d) obtaining at least one diluent; (e) obtaining at least one excipient; and (f) contacting dihydrooxyresveratrol, glycyrrhizic acid, at least one carrier, at least one diluent and at least one excipient to obtain a composition, wherein dihydrooxyresveratrol weight percentage in said composition is in the range of 0.0005 % - 0.0009 %, glycyrrhizic acid weight percentage in said composition is in the range of 0.001 % - 0.003 %, wherein said glycyrrhizic acid salt is an ammonium salt, and the dihydrooxyresveratrol to the glycyrrhizic acid and salts thereof w/w ratio in said composition is in the range of 1:2 - 1:4.
[071] In an embodiment of the present disclosure, there is provided a method of preparing a composition comprising: (a) obtaining dihydrooxyresveratrol having weight percentage of 0.000615 %; (b) obtaining glycyrrhizic acid salt having weight percentage of 0.002 %; (c) obtaining at least one carrier; (d) obtaining at least one diluent; (e) obtaining at least one excipient; and (f) contacting dihydrooxyresveratrol, glycyrrhizic acid and salts thereof, at least one carrier, at least one diluent and at least one excipient to obtain said composition, wherein said glycyrrhizic acid salt is an ammonium salt, and the dihydrooxyresveratrol to the glycyrrhizic acid and salts thereof w/w ratio in said composition is in the range of 1:2 - 1:4.

[072] In an embodiment of the present disclosure, there is provided a method of preparing a composition comprising: (a) obtaining dihydrooxyresveratrol; (b) obtaining glycyrrhizic acid and salts thereof; (c) obtaining at least one carrier; (d) obtaining at least one diluent; (e) obtaining at least one excipient; and (f) contacting dihydrooxyresveratrol, glycyrrhizic acid and salts thereof, at least one carrier, at least one diluent and at least one excipient to obtain said composition, wherein the dihydrooxyresveratrol to the glycyrrhizic acid and salts thereof w/w ratio in said composition is 1:3.2.
[073] In an embodiment of the present disclosure, there is provided a method of
preparing a composition comprising: (a) obtaining dihydrooxyresveratrol; (b)
obtaining glycyrrhizic acid and salts thereof; (c) obtaining at least one carrier; (d)
obtaining at least one diluent (e) obtaining at least one excipient; and (f) contacting
dihydrooxyresveratrol, glycyrrhizic acid and salts thereof, at least on carrier, at least
one diluent and at least one excipient to obtain said composition, wherein said
glycyrrhizic acid salts comprise organic salts and inorganic salts, and the
dihydrooxyresveratrol to the glycyrrhizic acid and salts thereof w/w ratio in said composition is 1:3.2.
[074] In an embodiment of the present disclosure, there is provided a method of preparing a composition comprising: (a) obtaining dihydrooxyresveratrol; (b) obtaining glycyrrhizic acid and salts thereof; (c) obtaining at least one carrier; (d) obtaining at least one diluent; (e) obtaining at least one excipient; and (e) contacting dihydrooxyresveratrol, glycyrrhizic acid and salts thereof, at least one carrier, at least one diluent and at least one excipient to obtain said composition, wherein said glycyrrhizic acid salt is an ammonium salt of glycyrrhizic acid, and the dihydrooxyresveratrol to the glycyrrhizic acid and salts thereof w/w ratio in said composition is 1:3.2.
[075] In an embodiment of the present disclosure, there is provided a method for preparing a composition comprising: (a) obtaining dihydrooxyresveratrol; (b) obtaining glycyrrhizic acid; (c) obtaining at least one carrier; (d) obtaining at least

one diluent (e) obtaining at least one excipient; and (f) contacting dihydrooxyresveratrol, glycyrrhizic acid, at least one carrier, at least one diluent and at least one excipient to obtain a composition, wherein dihydrooxyresveratrol weight percentage in said composition is in the range of 0.0005 % - 0.0009 %, glycyrrhizic acid weight percentage in said composition is in the range of 0.001 % - 0.003 %, and the dihydrooxyresveratrol to the glycyrrhizic acid and salts thereof w/w ratio in said composition is 1:3.2.
[076] In an embodiment of the present disclosure, there is provided a method of preparing a composition comprising: (a) obtaining dihydrooxyresveratrol; (b) obtaining glycyrrhizic acid; (c) obtaining at least one carrier; (d) obtaining at least one diluent; (e) at least one excipient; and (f) contacting dihydrooxyresveratrol, glycyrrhizic acid and salts thereof, at least one carrier, at least one diluent and at least one excipient to obtain said composition, wherein dihydrooxyresveratrol weight percentage in said composition is 0.000615 %, glycyrrhizic acid weight percentage in said composition is 0.002 %, and the dihydrooxyresveratrol to the glycyrrhizic acid and salts thereof w/w ratio in said composition is 1:3.2.
[077] In an embodiment of the present disclosure, there is provided a method for preparing a composition comprising: (a) obtaining dihydrooxyresveratrol; (b) obtaining glycyrrhizic acid; (c) obtaining at least one carrier; (d) obtaining at least one diluent; (e) obtaining at least one excipient; and (f) contacting dihydrooxyresveratrol, glycyrrhizic acid, at least one carrier, at least one diluent and at least one excipient to obtain said composition, wherein dihydrooxyresveratrol weight percentage in said composition is in the range of 0.0005 % - 0.0009 %, glycyrrhizic acid weight percentage in said composition is in the range of 0.001 % -0.003 %, wherein said glycyrrhizic acid salt is an ammonium salt of glycyrrhizic acid, and dihydrooxyresveratrol to glycyrrhizic acid and salts thereof w/w ratio in said composition is 1:3.2.
[078] In an embodiment of the present disclosure, there is provided a method of preparing a composition comprising: (a) obtaining dihydrooxyresveratrol; (b)

obtaining glycyrrhizic acid; (c) obtaining the at least one carrier; (d) obtaining the at least one diluent; (e) at least one excipient; and (f) contacting dihydrooxyresveratrol, glycyrrhizic acid and salts thereof, at least one carrier, at least one diluent, and at least one excipient to obtain said composition, wherein said glycyrrhizic acid salt is an ammonium salt of glycyrrhizic acid, and dihydrooxyresveratrol weight percentage in said composition is 0.000615%, glycyrrhizic acid weight percentage in said composition is 0.002%, and the dihydrooxyresveratrol to the glycyrrhizic acid and salts thereof w/w ratio in said composition is 1:3.2.
[079] In an embodiment of the present disclosure, there is provided a method of reducing skin pigmentation, said method comprising: (a) obtaining a composition comprising: (i) dihydrooxyresveratrol; and (ii) glycyrrhizic acid and salts thereof, wherein the dihydrooxyresveratrol to the glycyrrhizic acid and salts thereof w/w ratio in said composition is in the range of 1:2- 1:4; and (b) contacting said composition with skin, wherein said composition inhibits skin pigmentation.
[080] In an embodiment of the present disclosure, there is provided a method of reducing skin pigmentation, said method comprising: (a) obtaining a composition comprising: (i) dihydrooxyresveratrol; and (ii) glycyrrhizic acid and salts thereof; and (b) contacting said composition with skin, wherein said glycyrrhizic acid salts in said composition comprise organic salts and inorganic salts, the dihydrooxyresveratrol to the glycyrrhizic acid and salts thereof w/w ratio in said composition is in the range of 1:2- 1:4, and said composition inhibits skin pigmentation.
[081] In an embodiment of the present disclosure, there is provided a method of reducing skin pigmentation, said method comprising: (a) obtaining a composition comprising: (i) dihydrooxyresveratrol; and (ii) glycyrrhizic acid and salts thereof; and (b) contacting said composition with skin, wherein said glycyrrhizic acid salt is an ammonium salt of glycyrrhizic acid, the dihydrooxyresveratrol to the glycyrrhizic acid and salts thereof w/w ratio in said composition is in the range of 1:2 - 1:4, and said composition reduces skin pigmentation.

[082] In an embodiment of the present disclosure, there is provided a method of reducing skin pigmentation, said method comprising: (a) obtaining a composition comprising: (i) dihydrooxyresveratrol having weight percentage in the range of 0.0005 % - 0.0009 % in said composition; and (ii) glycyrrhizic acid salt having weight percentage of 0.002 % in said composition; and (b) contacting said composition with skin, wherein said composition reduces skin pigmentation, and the dihydrooxyresveratrol to the glycyrrhizic acid and salts thereof w/w ratio in said composition is in the range of 1:2 - 1:4.
[083] In an embodiment of the present disclosure, there is provided a method of reducing skin pigmentation, said method comprising: (a) obtaining a composition comprising: (i) dihydrooxyresveratrol having weight percentage in the range of 0.0005 % - 0.0009 % in said composition; and (ii) glycyrrhizic acid salt having weight percentage of 0.002 % in said composition; and (b) contacting said composition with skin, wherein said composition reduces skin pigmentation, said glycyrrhizic acid salt is an ammonium salt and dihydrooxyresveratrol to glycyrrhizic acid and salts thereof w/w ratio in said composition in the range of 1:2 - 1:4. [084] In an embodiment of the present disclosure, there is provided a method of reducing skin pigmentation, said method comprising: (a) obtaining a composition comprising: (i) dihydrooxyresveratrol; and (ii) glycyrrhizic acid and salts thereof, wherein the dihydrooxyresveratrol to the glycyrrhizic acid and salts thereof w/w ratio in said composition is 1:3.2; and (b) contacting said composition with skin, wherein said composition reduces skin pigmentation.
[085] In an embodiment of the present disclosure, there is provided a method of reducing skin pigmentation, said method comprising: (a) obtaining a composition comprising: (i) dihydrooxyresveratrol; and (ii) glycyrrhizic acid and salts thereof; and (b) contacting said composition with skin, wherein said glycyrrhizic acid salts comprise organic salts and inorganic salts, the dihydrooxyresveratrol to the glycyrrhizic acid and salts thereof w/w ratio in said composition is 1:3.2, and said composition reduces skin pigmentation.

[086] In an embodiment of the present disclosure, there is provided a method of reducing skin pigmentation, said method comprising: (a) obtaining a composition comprising: (i) dihydrooxyresveratrol; and (ii) glycyrrhizic acid and salts thereof; and (b) contacting said composition with skin, wherein said glycyrrhizic acid salt is an ammonium salt of glycyrrhizic acid, the dihydrooxyresveratrol to the glycyrrhizic acid and salts thereof w/w ratio in said composition is 1:3.2, and said composition reduces skin pigmentation.
[087] In an embodiment of the present disclosure, there is provided a method of reducing skin pigmentation, said method comprising: (a) obtaining a composition comprising: (i) dihydrooxyresveratrol having weight percentage in the range of 0.0005 % - 0.0009 % in said composition; and (ii) glycyrrhizic acid salt having weight percentage of 0.002 % in said composition; and (b) contacting said composition with skin, wherein said composition reduces skin pigmentation, and the dihydrooxyresveratrol to the glycyrrhizic acid and salts thereof w/w ratio in said composition is 1:3.2.
[088] In an embodiment of the present disclosure, there is provided a method of reducing skin pigmentation, said method comprising: (a) obtaining a composition comprising: (i) dihydrooxyresveratrol having weight percentage in the range of 0.0005 % - 0.0009 % in said composition; and (ii) glycyrrhizic acid salt having weight percentage of 0.002 % in said composition; and (b) contacting said composition with skin, wherein said composition reduces skin pigmentation, said glycyrrhizic acid salt is an ammonium salt and the dihydrooxyresveratrol to the glycyrrhizic acid and salts thereof w/w ratio in said composition is 1:3.2.
[089] In an embodiment of the present disclosure, there is provided a method of reducing skin pigmentation, said method comprising: (a) obtaining a composition comprising: (i) dihydrooxyresveratrol; (ii) glycyrrhizic acid and salts thereof; (iii) at least one carrier, (iv) at least one diluent; and (v) excipients, wherein the dihydrooxyresveratrol to the glycyrrhizic acid and salts thereof w/w ratio in said

composition is in the range of 1:2- 1:4; and (b) contacting said composition with skin, wherein said composition reduces skin pigmentation.
[090] In an embodiment of the present disclosure, there is provided a method of reducing skin pigmentation, said method comprising: (a) obtaining a composition comprising: (i) dihydrooxyresveratrol; (ii) glycyrrhizic acid and salts thereof; (iii) at least one carrier; (iv) at least one diluent; and (v) at least one excipient; and (b) contacting said composition with skin, wherein said glycyrrhizic acid salts comprise organic salts and inorganic salts, the dihydrooxyresveratrol to the glycyrrhizic acid and salts thereof w/w ratio in said composition is in the range of 1:2- 1:4, and said composition reduces skin pigmentation.
[091] In an embodiment of the present disclosure, there is provided a method of reducing skin pigmentation, said method comprising: (a) obtaining a composition comprising: (i) dihydrooxyresveratrol; (ii) glycyrrhizic acid and salts thereof; (iii) at least one carrier; (iv) at least one diluent; and (v) at least one excipient; and (b) contacting said composition with skin, wherein said glycyrrhizic acid salt is an ammonium salt of glycyrrhizic acid, the dihydrooxyresveratrol to the glycyrrhizic acid and salts thereof w/w ratio in said composition is in the range of 1:2- 1:4, and said composition reduces skin pigmentation.
[092] In an embodiment of the present disclosure, there is provided a method of reducing skin pigmentation, said method comprising: (a) obtaining a composition comprising: (i) dihydrooxyresveratrol having weight percentage in the range of 0.0005% - 0.0009% in said composition; (ii) glycyrrhizic acid having weight percentage in the range of 0.002% - 0.003% in said composition; (iii) at least one carrier; (iv) at least one diluent and (v) at least one excipient; and (b) contacting said composition with skin, wherein said composition reduces skin pigmentation, and the dihydrooxyresveratrol to the glycyrrhizic acid and salts thereof w/w ratio in said composition is in the range of 1:2- 1:4.
[093] In an embodiment of the present disclosure, there is provided a method of reducing skin pigmentation, said method comprising: (a) obtaining a composition

comprising: (i) dihydrooxyresveratrol having weight percentage in the range of 0.0005% - 0.0009% in said composition; (ii) glycyrrhizic acid having weight percentage in the range of 0.002% - 0.003% in said composition; (iii) at least one carrier; (iv) at least one diluent; and (v) at least one excipient; and (b) contacting said composition with skin, wherein said composition reduces skin pigmentation, said glycyrrhizic acid salt is an ammonium salt of glycyrrhizic acid, and the dihydrooxyresveratrol to the glycyrrhizic acid and salts thereof w/w ratio in said composition is in the range of 1:2 - 1:4.
[094] In an embodiment of the present disclosure, there is provided a method of reducing skin pigmentation, said method comprising: (a) obtaining a composition comprising: (i) dihydrooxyresveratrol; (ii) glycyrrhizic acid and salts thereof; (iii) at least one carrier; (iv) at least one diluent; and (v) at least one excipient; and (b) contacting said composition with skin, wherein the dihydrooxyresveratrol to the glycyrrhizic acid and salts thereof w/w ratio in said composition is 1:3.2, and said composition reduces skin pigmentation.
[095] In an embodiment of the present disclosure, there is provided a method of reducing skin pigmentation, said method comprising: (a) obtaining a composition comprising: (i) dihydrooxyresveratrol; (ii) glycyrrhizic acid and salts thereof; (iii) at least one carrier; (iv) at least one diluent; and (v) at least one excipient; and (b) contacting said composition with skin, wherein said glycyrrhizic acid salts comprise organic salts and inorganic salts, the dihydrooxyresveratrol to the glycyrrhizic acid and salts thereof w/w ratio in said composition is 1:3.2, and said composition reduces skin pigmentation.
[096] In an embodiment of the present disclosure, there is provided a method of reducing skin pigmentation, said method comprising: (a) obtaining a composition comprising: (i) dihydrooxyresveratrol; (ii) glycyrrhizic acid and salts thereof; (iii) at least one carrier; (iv) at least one diluent; and (v) at least one excipient; and (b) contacting said composition with skin, wherein said glycyrrhizic acid salt is an ammonium salt of glycyrrhizic acid, the dihydrooxyresveratrol to the glycyrrhizic

acid and salts thereof w/w ratio in said composition is 1:3.2, and said composition reduces skin pigmentation.
[097] In an embodiment of the present disclosure, there is provided a method of reducing skin pigmentation, said method comprising: (a) obtaining a composition comprising: (i) dihydrooxyresveratrol having weight percentage in the range of 0.0005% - 0.0009% in said composition; (ii) glycyrrhizic acid having weight percentage in the range of 0.001% - 0.003% in said composition; (iii) at least one carrier; (iv) at least one diluent; and (v) at least one excipient; and (b) contacting said composition with skin, wherein said composition reduces skin pigmentation, and the dihydrooxyresveratrol to the glycyrrhizic acid and salts thereof w/w ratio in said composition is 1:3.2.
[098] In an embodiment of the present disclosure, there is provided a method of
reducing skin pigmentation, said method comprising: (a) obtaining a composition
comprising: (i) dihydrooxyresveratrol having weight percentage in the range of
0.0005% - 0.0009% in said composition; (ii) glycyrrhizic acid having weight
percentage in the range of 0.001% - 0.003% in said composition; (iii) at least one
carrier; (iv) at least one diluent; and (e) at least one excipient; and (b) contacting said
composition with skin, wherein said composition reduces skin pigmentation, said
glycyrrhizic acid salt is an ammonium salt of glycyrrhizic acid, and the
dihydrooxyresveratrol to the glycyrrhizic acid and salts thereof w/w ratio in said composition is 1:3.2.
[099] In an embodiment of the present disclosure, there is provided a composition comprising: (a) dihydrooxyresveratrol; and (b) glycyrrhizic acid and salts thereof, wherein said composition reduces skin pigmentation by reducing melanin production and the dihydrooxyresveratrol to the glycyrrhizic acid and salts thereof w/w ratio in said composition is in the range of 1:2 - 1:4.
[100] In an embodiment of the present disclosure, there is provided a composition comprising: (a) dihydrooxyresveratrol; and (b) glycyrrhizic acid and salts thereof, wherein said composition reduces skin pigmentation by reducing melanin production

and the dihydrooxyresveratrol to the glycyrrhizic acid and salts thereof w/w ratio in said composition is 1:3.2.
[101] In an embodiment of the present disclosure, there is provided a composition comprising: (a) dihydrooxyresveratrol; and (b) glycyrrhizic acid and salts thereof, wherein said composition reduces skin pigmentation by reducing melanin production, said glycyrrhizic acid salts comprise organic salts and inorganic salts and the dihydrooxyresveratrol to the glycyrrhizic acid and salts thereof w/w ratio in said composition is in the range of 1:2 - 1:4.
[102] In an embodiment of the present disclosure, there is provided a composition comprising: (a) dihydrooxyresveratrol; and (b) glycyrrhizic acid and salts thereof, wherein said composition reduces skin pigmentation by reducing melanin production, said glycyrrhizic acid salts comprise organic salts and inorganic salts, and the dihydrooxyresveratrol to the glycyrrhizic acid and salts thereof w/w ratio in said composition is 1:3.2.
[103] In an embodiment of the present disclosure, there is provided a composition comprising: (a) dihydrooxyresveratrol; and (b) glycyrrhizic acid and salts thereof, wherein said composition reduces skin pigmentation by reducing melanin production, said glycyrrhizic acid salt comprises an ammonium salt of glycyrrhizic acid, and the dihydrooxyresveratrol to the glycyrrhizic acid and salts thereof w/w ratio in said composition is in the range of 1:2 - 1:4.
[104] In an embodiment of the present disclosure, there is provided a composition comprising: (a) dihydrooxyresveratrol; and (b) glycyrrhizic acid and salts thereof, wherein said composition reduces skin pigmentation by reducing melanin production, said glycyrrhizic acid salt comprises an ammonium salt of glycyrrhizic acid, and the dihydrooxyresveratrol to the glycyrrhizic acid and salts thereof w/w ratio in said composition is 1:3.2.
[105] In an embodiment of the present disclosure, there is provided a composition comprising: (a) dihydrooxyresveratrol having weight percentage in said composition in the range of 0.0005%- 0.0009%; and (b) glycyrrhizic acid salt having weight

percentage in said composition in the range of 0.001%- 0.003%, wherein said composition reduces skin pigmentation by reducing melanin production, and the dihydrooxyresveratrol to the glycyrrhizic acid and salts thereof w/w ratio in said composition is in the range of 1:2- 1:4.
[106] In an embodiment of the present disclosure, there is provided a composition comprising: (a) dihydrooxyresveratrol having weight percentage in said composition in the range of 0.0005%- 0.0009%; and (b) glycyrrhizic acid salt having weight percentage in said composition in the range of 0.001%- 0.003%, wherein said composition reduces skin pigmentation by reducing melanin production, and the dihydrooxyresveratrol to the glycyrrhizic acid and salts thereof w/w ratio in said composition is 1:3.2.
[107] In an embodiment of the present disclosure, there is provided a composition comprising: (a) dihydrooxyresveratrol; (b) glycyrrhizic acid and salts thereof; (c) at least one carrier; (d) at least one diluent; and (e) at least one excipient, wherein said composition reduces skin pigmentation by reducing melanin production, and the dihydrooxyresveratrol to the glycyrrhizic acid and salts thereof w/w ratio in said composition is in the range of 1:2- 1:4.
[108] In an embodiment of the present disclosure, there is provided a composition comprising: (a) dihydrooxyresveratrol; (b) glycyrrhizic acid and salts thereof; (c) at least one carrier; (d) at least one diluent; and (e) at least one excipient, wherein said composition reduces skin pigmentation by reducing melanin production, and the dihydrooxyresveratrol to the glycyrrhizic acid and salts thereof w/w ratio in said composition is 1:3.2.
[109] In an embodiment of the present disclosure, there is provided a composition comprising: (a) dihydrooxyresveratrol; (b) glycyrrhizic acid and salts thereof; (c) at least one carrier; (d) at least one diluent; and (e) at least one excipient, wherein said composition reduces skin pigmentation by reducing melanin production, said glycyrrhizic acid salts comprise organic salts and inorganic salts, and the

dihydrooxyresveratrol to the glycyrrhizic acid and salts thereof w/w ratio in said composition is in the range of 1:2 - 1:4.
[110] In an embodiment of the present disclosure, there is provided a composition comprising: (a) dihydrooxyresveratrol; (b) glycyrrhizic acid and salts thereof; (c) at least one carrier; (d) at least one diluent; and (e) at least one excipient, wherein said composition reduces skin pigmentation by reducing melanin production, said glycyrrhizic acid salts comprise organic salts and inorganic salts and the dihydrooxyresveratrol to the glycyrrhizic acid and salts thereof w/w ratio in said composition is 1:3.2.
[111] In an embodiment of the present disclosure, there is provided a composition comprising: (a) dihydrooxyresveratrol; (b) glycyrrhizic acid and salts thereof; (c) at least one carrier; (d) at least one diluent; and (e) at least one excipient, wherein said composition reduces skin pigmentation by reducing melanin production, said glycyrrhizic acid salt comprises an ammonium salt of glycyrrhizic acid, and dihydrooxyresveratrol to glycyrrhizic acid and salts thereof w/w ratio in said composition is in the range of 1:2- 1:4.
[112] In an embodiment of the present disclosure, there is provided a composition comprising: (a) dihydrooxyresveratrol; (b) glycyrrhizic acid and salts thereof; (c) at least one carrier; (d) at least one diluent and (e) at least one excipient, wherein said composition reduces skin pigmentation by reducing melanin production, said glycyrrhizic acid salt comprises an ammonium salt of glycyrrhizic acid, and the dihydrooxyresveratrol to the glycyrrhizic acid and salts thereof w/w ratio in said composition is 1:3.2.
[113] In an embodiment of the present disclosure, there is provided a composition comprising: (a) dihydrooxyresveratrol having weight percentage in said composition in the range of 0.0005%- 0.0009%; (b) glycyrrhizic acid salt having weight percentage in said composition in the range of 0.001%- 0.003%; (c) at least one carrier; (d) at least one diluent; and (e) at least one excipient, wherein said composition reduces skin pigmentation by reducing melanin production, and the

dihydrooxyresveratrol to the glycyrrhizic acid and salts thereof w/w ratio in said composition is in the range of 1:2- 1:4.
[114] In an embodiment of the present disclosure, there is provided a composition comprising: (a) dihydrooxyresveratrol having weight percentage in said composition in the range of 0.0005%- 0.0009%; (b) glycyrrhizic acid having weight percentage in said composition in the range of 0.001%- 0.003%; (c) at least one carrier; (d) at least one diluents and (e) at least one excipient, wherein said composition reduces skin pigmentation by reducing melanin production, and the dihydrooxyresveratrol to the glycyrrhizic acid and salts thereof w/w ratio in said composition is 1:3.2.
[115] In an embodiment of the present disclosure, there is provided a composition comprising: (a) dihydrooxyresveratrol having weight percentage in said composition in the range of 0.0005%- 0.0009%; (b) glycyrrhizic acid salt having weight percentage in said composition in the range of 0.001%- 0.003%; (c) at least one carrier, (d) at least one diluent; and (e) at least one excipient, wherein said composition reduces skin pigmentation by reducing melanin production, said glycyrrhizic acid salt is an ammonium salt and dihydrooxyresveratrol to glycyrrhizic acid and salts thereof w/w ratio in said composition is in the range of 1:2- 1:4. [116] In an embodiment of the present disclosure, there is provided a composition comprising: (a) dihydrooxyresveratrol having weight percentage in said composition in the range of 0.0005%- 0.0009%; (b) glycyrrhizic acid having weight percentage in said composition in the range of 0.001%- 0.003%; (c) at least one carrier, (d) at least one diluent; and (e) at least one excipient, wherein said composition reduces skin pigmentation by reducing melanin production, said glycyrrhizic acid salt is an ammonium salt, and the dihydrooxyresveratrol to the glycyrrhizic acid and salts thereof w/w ratio in said composition is 1:3.2.
[117] 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
[118] 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 vary.
Example 1
Materials and methods
[119] Dihydrooxyresveratrol was procured from Sami labs, glycyrrhizic acid or
liquorice root extract from sigma, human adult primary melanocytes (HEMa) from
LONZA, and cellular viability kit from Invitrogen.
[120] Method of preparation of a composition comprising dihydrooxyresveratrol
and glycyrrhizic acid: Dihydrooxyresveratrol and glycyrrhizic acid at particular
concentrations were dissolved in a DMSO (dimethyl sulfoxide). Further, the
composition may comprise additives, but not limited to, emollients, pH adjusters,
preservatives, and any other cosmetically suitable ingredient in order to formulate
various recipes for topical application and/or delivery. Such methodologies are
known to a person of ordinary skill in the art.

Example 2
Cytotoxicity analysis of the actives
[121] To determine the concentration ranges appropriate for analysis of actives on cellular functions, cytotoxicity experiments were conducted with both the actives.The cell viability was determined using an MTT assay. The cells were seeded in to 96 well plate at density of 2.5x 103 ell per well. After 24 hr of incubation, the culture medium was removed and a new medium containing the test substance (incubated with different concentrations of dihydrooxyresveratrol (0.000615, 0.0012, 0.0024 and 0.0048 %), glycyrrhizic acid (0.002, 0.004, 0.008, 0.016 %) added to each well in quintuplicate, after 3 days of incubation, the cell viability of was assayed using an MTT solutions. The percentage of viability cells in each well were calculated relative to the optical density (OD) value of living cells. The cell viability was determined using an MTT assay. The cells were seeded in to 96 well plate at density of 2.5x 103 ell per well. After 24 hr of incubation, the culture medium was removed and a new medium containing the test substance (incubated with different concentrations of dihydrooxyresveratrol (0.000615, 0.0012, 0.0024 and 0.0048 %), glycyrrhizic acid (0.002, 0.004, 0.008, 0.016 %) added to each well in quintuplicate, after 3 days of incubation, the cell viability of was assayed using an MTT solutions. The percentage of viability cells in each well were calculated relative to the optical density (OD) value of living cells in the control group (100%). he control group (100%). [122] Figure 1 depicts the effect of dihydrooxyresveratrol on the viability of HEMa cells, cytotoxicity assay showed that overall, dihydrooxyresveratrol was non-toxic at most of the concentrations tested with average viability 102 %. Based on these results, a non-toxic range of 0.000615% - 0.0024% was chosen for further analysis. [123] Figure 2 depicts the effect of glycyrrhizic acid on the viability of HEMa cells, cytotoxicity assay showed that overall, glycyrrhizic acid was non-toxic at most of the concentrations tested with average viability 104 %. Based on these results, a non-toxic range of 0.002% - 0.008% was chosen for further analysis.
Example 3

Evaluation of a combination of dihydrooxyresveratrol and glycyrrhizic acid on percent inhibition of melanin
[124] Following the observations obtained with the cytotoxicity data, different w/w ratios of dihydrooxyresveratrol to glycyrrhizic acid were analysed for the effect of this combination on percent inhibition of melanin. Unexpectedly and surprisingly, a higher percent inhibition of melanin was obtained at a w/w ratio of 1:3.2 of dihydrooxyresveratrol to glycyrrhizic acid (Figure 3). This combination resulted in approximately 45 % inhibition of melanocytes, which is approximately four fold higher than the dihydrooxyresveratrol alone with same concentration (10 % inhibition) and approximately three fold higher than glycyrrhizic acid alone (15 % inhibition). The combinatorial effect of the actives as compared to that of the actives alone, showed significantly higher. Thus, distinct synergism is apparent in the combination of dihydrooxyresveratrol and glycyrrhizic acid.
[125] Additionally, synergism is only observed at the unique w/w ratio of 1:3.2 of dihydrooxyresveratrol to glycyrrhizic acid, at the weight percentage of 0.000615% dihydrooxyresveratrol and 0.002% glycyrrhizic acid. As seen in Figure 3, the combination of the two at a 1:3.33 w/w ratio of dihydrooxyresveratrol to glycyrrhizic acid, at the weight percentages of 0.0012% dihydrooxyresveratrol and 0.004% glycyrrhizic acid does not show the same effect.
[126] Overall, the present disclosure provides a novel composition of dihydrooxyresveratrol and glycyrrhizic acid, which exhibits a surprising and unexpected synergistic effect on inhibition of melanin within a w/w range of 1:2- 1:4 of dihydrooxyresveratrol to glycyrrhizic acid, and more specifically at a 1: 3.2 w/w ratio of dihydrooxyresveratrol to glycyrrhizic acid. Thus, the combination of dihydrooxyresveratrol and glycyrrhizic acid shows synergism in inhibiting melanin and thus can be used for the management skin problems like skin aging and pigmentation. Further, the identification of this novel combination for the management of skin problems functions only at specific concentrations and ratios and

thus cannot be arrived at without undue experimentation, and is thus not obvious to a person skilled in the art.

I/We claim:
1. A composition to reduce skin pigmentation comprising:
(a) dihydrooxyresveratrol; and
(b) glycyrrhizic acid and salts thereof,
wherein dihydrooxyresveratrol to glycyrrhizic acid and salts thereof w/w ratio in said composition is in the range of 1:2- 1:4.
2. The composition as claimed in claim 1, wherein said salts of glycyrrhizic acid comprise organic salts and inorganic salts.
3. The composition as claimed in claim 1, wherein said glycyrrhizic acid salt is an ammonium salt of glycyrrhizic acid.
4. The composition as claimed in claim 1-3, wherein dihydrooxyresveratrol weight percentage in said composition is in the range of 0.0005%- 0.0009%, and glycyrrhizic acid weight percentage in said composition is in the range of 0.001%- 0.003%.
5. The composition as claimed in claim 4, wherein dihydrooxyresveratrol weight percentage in said composition is 0.000615%, and glycyrrhizic acid weight percentage in said composition is 0.002%.
6. The composition as claimed in claim 1, further comprising at least one carrier, at least one diluent, and at least one excipient.
7. A method of preparing a composition as claimed in any of the claims 1-5, said method comprising:

(a) obtaining dihydrooxyresveratrol;
(b) obtaining glycyrrhizic acid and salts thereof; and
(c) contacting dihydrooxyresveratrol, glycyrrhizic acid and salts thereof to obtain said
composition.
8. A method of preparing a composition as claimed in claim 6, said method
comprising:
(a) obtaining dihydrooxyresveratrol;
(b) obtaining glycyrrhizic acid and salts thereof;
(c) obtaining at least one carrier;

(d) obtaining at least one diluent;
(e) obtaining at least one excipient; and
(d) contacting dihydrooxyresveratrol, glycyrrhizic acid and salts thereof, the at least one carrier, at least one diluent, and at least one excipient, to obtain said composition.
9. A method of reducing skin pigmentation, said method comprising:
(a) obtaining a composition as claimed in any of the claims 1-6; and
(b) contacting said composition with skin,
wherein said composition reduces skin pigmentation.
10. The composition as claimed in any of claims 1-6, wherein said composition
reduces skin pigmentation by reducing melanin production.

Documents

Application Documents

# Name Date
1 Form 5 [29-03-2017(online)].pdf 2017-03-29
2 Form 3 [29-03-2017(online)].pdf 2017-03-29
3 Drawing [29-03-2017(online)].pdf 2017-03-29
4 Description(Complete) [29-03-2017(online)].pdf_171.pdf 2017-03-29
5 Description(Complete) [29-03-2017(online)].pdf 2017-03-29
6 Other Patent Document [16-05-2017(online)].pdf 2017-05-16
7 Form 26 [16-05-2017(online)].pdf 2017-05-16
8 Correspondence by Agent_Power Of Attorney_18-05-2017.pdf 2017-05-18
9 Correspondence by Agent_Form1_18-05-2017.pdf 2017-05-18
10 201741011249-FORM 18 [24-03-2021(online)].pdf 2021-03-24
11 201741011249-FER.pdf 2021-10-17
12 201741011249-OTHERS [29-11-2021(online)].pdf 2021-11-29
13 201741011249-FER_SER_REPLY [29-11-2021(online)].pdf 2021-11-29
14 201741011249-DRAWING [29-11-2021(online)].pdf 2021-11-29
15 201741011249-ABSTRACT [29-11-2021(online)].pdf 2021-11-29
16 201741011249-FORM 3 [30-11-2021(online)].pdf 2021-11-30
17 201741011249-US(14)-HearingNotice-(HearingDate-05-05-2022).pdf 2022-04-19
18 201741011249-Correspondence to notify the Controller [03-05-2022(online)].pdf 2022-05-03
19 201741011249-Written submissions and relevant documents [18-05-2022(online)].pdf 2022-05-18
20 201741011249-PatentCertificate29-06-2022.pdf 2022-06-29
21 201741011249-IntimationOfGrant29-06-2022.pdf 2022-06-29

Search Strategy

1 201741011249searchreportE_30-03-2021.pdf

ERegister / Renewals

3rd: 02 Aug 2022

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4th: 02 Aug 2022

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5th: 02 Aug 2022

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6th: 02 Aug 2022

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7th: 02 Aug 2022

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8th: 10 Feb 2024

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9th: 03 Feb 2025

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