TECHNICAL FIELD
[001] The subject matter described herein in general relates to the field of hair growth compositions, and in particular relates to interleukin inhibitor compositions for promoting hair growth. BACKGROUND OF INVENTION
[002] Anti-inflammatory cytokine, interleukin (IL)-4, has been shown to induce apoptosis in cultured follicular keratinocytes, but not in the dermal papilla cells, in dose- and time-dependent manner. This IL-4 mediated apoptosis may participate in regulating catagen formation in the hair follicle, acting selectively on cultured follicular keratinocytes. (Mandt N et al, 2002, Eur. J. Dermatol. 12(5): 432-8). Literature suggests that's that there is a correlation between biotin levels and the IL-4 levels in a human body. Biotin deficiency in humans causes pathological changes in skin and its appendages like hair and nail, some of which include exfoliative dermatitis, depigmentation and alopecia. At molecular level, biotin supplementation improves cytokeratin expression, glucokinase expression, sGC and PKG activation, and decreases expression of gene interleukin (TL)-4. Decrease in IL-4 expression may slower or inhibit the IL-4 mediated signaling pathway, thereby treating conditions such as, atopic dermatitis, autoimmune disorders, skin and disorders, that characterized by over expression of IL-4. [003] Several clinical studies also demonstrated improvement of hair and nail growth upon supplementation with biotin. For example, US4584191 discloses hair care compositions containing biotin ethyl ester in combination with a compatible carrier material. WO2013167927 discloses injectable composition for treating hair loss comprising biotin, minerals and oligo- elements, organic silicon, pentoxifylline, and procaine hydrochloride. WO2016122172 discloses a pharmaceutical composition containing melatonin, dex, panthenol, biotin and nicotinamide as active ingredients for hair health or hair growth promotion. [004] Although numerous compositions, derived from plant sources, have been described in the past, there still is a continuing interest in providing novel hair growth compositions which demonstrate efficacy in improving hair volume and stimulating hair growth.

SUMMARY OF THE INVENTION
[005] In an aspect of the present invention, there is provided a composition
comprising: a) naringenin; b) genistein; c) coenzyme Q10; and d) biotin, wherein
naringenin to genistein to coenzyme Q10 weight ratio in said composition is in a
range of 0.75-1.25: 0.75-1.25: 0.75-1.25.
[006] In another aspect of the present invention, there is provided a process for
preparing a composition comprising: a) naringenin; b) genistein; c) coenzyme Q10;
and d) biotin, wherein naringenin to genistein to coenzyme Q10 weight ratio in said
composition is in a range of 0.75-1.25: 0.75-1.25: 0.75-1.25; said process
comprising: i) obtaining naringenin; ii) obtaining genistein; iii) obtaining coenzyme
Q10; iv) obtaining biotin; and v) contacting naringenin, genistein, coenzyme Q10,
and biotin to obtain the composition.
[007] These and other features, aspects, and advantages of the present subject
matter will be better understood with reference to the following description and
appended claims. This summary is provided to introduce a selection of concepts in
a simplified form. This summary is not intended to identify key features or
essential features of the claimed subject matter, nor is it intended to be used to limit
the scope of the claimed subject matter.
BRIEF DESCRIPTION OF THE DRAWINGS
[008] The detailed description is described with reference to the accompanying
figures. The same numbers are used throughout the drawings to reference like
features and components.
[009] Figure 1 depicts the effect of biotin individually, and in combination with
actives (naringenin, genistein, and coenzyme Q10) at a defined w/w ratio, on
interleukin (IL)-4 gene expression, in accordance with an embodiment of the
present subject matter.
[0010] Figure 2 depicts the effect of composition comprising naringenin, genistein,
biotin, and coenzyme Q10 at varying w/w ratios on IL - 4 gene expressions, in
accordance with an embodiment of the present subject matter.
[0011] Figure 3 depicts gene expression analysis often genes on Sequencing Bead
Array (SB A), in accordance with an embodiment of the present subject matter.

[0012] Figure 4 depicts gene expression analysis of nine genes on SAB array, in
accordance with an embodiment of the present subject matter.
[0013] Figure 5 depicts the effect of composition of the present disclosure on
Bcl2/Bax gene ratio, in accordance with an embodiment of the present subject
matter.
[0014] Figure 6 depicts an in vitro hair growth assay, in accordance with an
embodiment of the present subject matter.
DETAILED DESCRIPTION OF THE INVENTION
[0015] 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 all combinations of any or more of such steps or features.
Definitions
[0016] 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.
[0017] 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.
[0018] 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".
[0019] 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.
[0020] The term "including" is used to mean "including but not limited to".
"Including" and "including but not limited to" are used interchangeably.
[0021] 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.
[0022] The term "at least one" is used to mean one or more and thus includes
individual components as well as mixtures/combinations.
[0023] For the purposes of the present disclosure, the term "transparent" refers to
allowing light to pass through so that objects behind can be distinctly seen.
[0024] For the purposes of the present disclosure, the terms "thickener",
"humectant", "emulsifier", "hair oil", "neutralizer", "soothing agent",
"preservative", "revitalizing agent", "conditioning agent", "moisturizing agent",
"antidandruff agent", "hair cell stimulator", "diluent", "silicone oil", "antioxidant",
refer to the generally known components used in the art. The specific components
of the above-described categories have been mentioned in the present disclosure
wherever applicable. Wherever not mentioned, it can be construed that any
component falling under the categories can be used as part of the composition.
[0025] 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.
[0026] 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. [0027] Hair follicles cycle through three successive stages termed, anagen, catagen and telogen. Anagen, the growing stage of scalp hair follicle lasts about 2-7 years followed by catagen, the regression phase and telogen, the resting phase. At catagen stage, hair follicle detaches from hair bulb (dermal papilla) and this stage lasts for 2-4 weeks. Telogen is the resting phase and at this stage the detached hair (during catagen) falls off and the hair follicle unit rests for about 3 months. In general, on a healthy scalp, about 85-90% of hair follicles will be in anagen stage, while 10-15% remain in telogen stage. Generally, hair loss can be due to several factors including, internal factors like body physiology, hormonal changes, alopecia, androgenetic alopecia, diseases and stress, and external factors like lifestyle, excessive abrasion of scalp and pollution, to name a few. While, some low hair loss is common and part of a healthy life, excessive hair loss is not healthy. Promoting hair growth and minimizing hair loss are of paramount importance both for health and economic reasons.
[0028] Coordinated action of various biological pathways and molecules orchestrate the hair follicle cycle (Alonso and Fuchs, 2005, J. Cell Sci. 2006 119: 391-393; Rishikaysh et al., 2014, Int. J. Mol. Sci. 15: 1647-1670), and dysregulation of these pathways leads to abnormalities. Prominent pathways involved in hair biology include WNT, hedgehog, notch and bone morphogenetic protein (BMP) signaling. Proper positioning and placing of hair follicles is mediated by ectodysplasin A receptor (EDAR)-BMP signaling and their transcriptional interactions (Mou et al., 2006. Proc. Natl. Acad. Sci. 103: 9075-9080). Vascular endothelial growth factor (VEGF)-mediated angiogenesis controls hair follicle size and growth (Yano et al., J. Clin. Invest. 2001, 107(4): 409-417). Sonic hedgehog signaling (Callahan et al., 2004, Genes Dev. 18(22): 2724-2729; Mill et al., 2003, Genes Dev. 17: 282-294; St-Jacques et al., 1998, Curr. Biol. 8(19): 1058-1068) is essential for anagen initiation. Few other molecules required for maintenance of anagen include SGK3 and MSX2 (Alonso et al., 2005, J. Cell Biol. 170(4): 559-570; Ma et al., 2003, Development. 130: 379-389). Some growth

factors essential for anagen include insulin-like growth factor (IGF), epidermal growth factor (EGF), fibroblast growth factor (FGF) and platelet derived growth factor (PDGF) (Sten and Pauss, 2001. Physiol. Rev. 81: 449-494). BMP signaling is essential in hair follicle differentiation (Botchkarev et al., 1999, Nat. Cell Biol. 1: 158-164; Kulessa et al., 2000, EMBO J. 19: 6664-6674), hair follicle morphogenesis, postnatal regeneration, modulating hair follicle cycling, hair matrix precursor cell proliferation and differentiation (Botchkare and Kishimoto, 2003. J. Investig. Dermatol. Symp. Proc. 8:46-55). Noggin is an inhibitor of BMPs and expressed by the mesenchyme. It is involved in hair follicle morphogenesis in embryos and promotes hair growth postnatally (Jamora et al., 2003. Nature. 422: 317-322; Kobielak et al., 2003. J. Cell Biol. 163: 609-623). Enhanced BMP signal activation or targeted inactivation of Noggin (BMP antagonist) results in significantly retarded hair follicle induction and progressive baldness (Botchkarev et al., 1999. Nature Cell Biol. 1: 158-164). Signaling by WNT-beta catenin proteins (Gat et al., 1998, Cell. 95: 605-614; Huelsken et al., 2001, Cell. 105: 533-545; Lo Celso et al., 2004, Development. 131: 1787-1799; Lowry et al., 2005, Genes Dev. 19: 1596-1611; Van Mater et al., 2003, Genes Dev. 17: 1219-1224; Zhang et al.,2009, Dev. Cell. 17: 49-61); Rabbani et al., 2011, Cell. 145: 941-955) and WNT proteins including WNT3a, WNT5a, WNTlOa, WNTlOb, frizzled7, disheveled 2, GSK3P, P-catenin and LEF1 are known to be associated in hair follicle development (Kishimoto et al., 2000, Genes Dev. 14: 1181-1185). The PDGFRA gene encodes platelet-derived growth factor receptor alpha (PDGFRA), which belongs to the family of receptor tyrosine kinases. The signaling pathway stimulated by PDGFRA controls many important cellular processes such as cell growth and division and cell survival. During hair follicle induction, to counteract the BMP inhibition, epithelial PDGF activates mesenchymal Platelet derived growth factor receptor alpha (PDGFRa). This, in combination with Sonic hedgehog (SUH) signaling activates Noggin secretion by mesenchymal (dermal) cells, which in turn inhibits BMP signaling to promote induction, organogenesis and cellular differentiation (Gao et al., 2008, Genes Dev. 22: 2111-2124).

[0029] Transition from anagen to catagen stage is mediated by growth factors like FGF5 and EGF, neurotrophins like BDNF and TFG beta family proteins like TFGP and BMPRIa (Andl et al., 2004, Development. 131: 2257-2268; Foitzik et al.,
2000, FASEB J. 14: 752-760; Hansen et al., 1997, Am. J. Pathol. 150: 1959-1975;
Hebert et al., 1994, Cell. 78: 1017-1025; Schmidt-Ullrich and Paus, 2005,
Bioessays. 27: 247-261). During quiescence (catagen and telogen), hair follicle
stem cells reside in hair bulge (Cotsarelis et al., 1990, Cell. 61: 1329-1337) and
actively proliferate during transition from catagen to anagen stage. Several genes
currently used as biomarkers of stem cell proliferation and differentiation are also
essential in hair biology. CK19 is expressed during hair follicle budding in fetal
and adult hair follicles (Schirren et al., 1997. Am. J. Dermatopathol. 19(4): 335-
40). Recently it has been shown that the stem cells contribute to balding. The bald
scalp although retains hair follicle stem cells, lacks CD200-rich and CD34-rich hair
follicle progenitor cells (Garza et al., 2011, J. Clin. Invest. 121(2): 613-22).
[0030] The telogen to anagen transition is facilitated by dermal papilla and hair
follicle cell cross talk and interplay between WNT pathway, and BMP inhibitory
factors (Kulessa et al., 2000. EMBO J. 19: 6664-6674; Greco et al., 2009. Cell
Stem Cell. 4: 155-169; Rabbani et al., 2011, Cell. 145: 941-955; Botchkarev et al.,
2001. FASEB J. 15: 2205-2214; Zhang et al., 2006, Stem Cells. 24: 2826-2839;
Enshell-Sejiffers et al., 2010, Dev. Cell. 18: 633-642). The hair follicle biology is
complex interplay between various pathways and many of these molecules can be
used as biomarkers in hair growth, and hair care product development. The effect
of some of the most important genes on hair growth and their function in hair
follicle cycle is herewith provided below in Table 1.

[0031] Conventional methods to stimulate hair growth include laser-treatments that involve tedious procedures which are expensive, and cumbersome. Certain other conventional methods include administration of drugs such as minoxidil which are associated with several side effects. Certain other conventional methods involve the use of soy protein isolates or powdered protein isolates that are known to have adverse effects on hair growth. Dietary supplements, vitamins, and plant source extracts for healthy growth of hair and nails are ineffective once the end user stops consumption of these supplements. Therefore, there still exists a need to develop

novel compositions that overcome the drawbacks associated with prior art. Accordingly, the composition of the present disclosure is to develop a cost-effective hair growth composition derived from plant sources that can effectively promote hair volume and growth. Accordingly, the present disclosure provides for a composition comprising naringenin, genistein, biotin, and coenzyme Q10, which when used in defined w/w ratios is effective in inhibiting IL-4 production, and consequently lower the induction of apoptosis in follicular keratinocytes that responsible for hair and nail growth.
[0032] Naringenin is a flavanone found mainly in variety of herbs and fruits, predominantly in grape fruit. It is known to have anti-inflammatory and analgesic effects. In addition, it has been shown to induce cell proliferation, protect against oxidative damage, induce vascular endothelial growth factor in hair follicle dermal papilla cells, and human keratinocytes (Kumar and Pandey, 2013, The Scientific World Journal. Article No. 162750).
[0033] Genistein is a phytoestrogen belonging to the subgroup of isoflavones. It is commonly found in several plants like, lupin, favabeans, soyabeans, kudzu, psoralea, coffee, and two species of shrubs, Flemingia vestita and Fleminga macrophylla. Genistein is a potent inhibitor of protein-tyrosine kinase and topoisomerase-II and used as antineoplastic and antitumor active. [0034] Ubiquinone-50, also referred as coenzyme Q10 is a well-known cosmetic agent especially in skin care mainly due to its antioxidant potential. In cultured hair follicle keratinocytes, coenzyme Q10 stimulates hair keratin genes that are down-regulated during anti-aging process of hair follicles. In placebo-controlled clinical study in human volunteers of over 40 years, shampoo and tonic enriched with CoQIO enhanced the hair keratin gene expression (Giesen et al., 2009, Int. J. Cosmetic Sci. 31(2): 154-155) showing its potential as a hair growth active. [0035] Biotin, also termed as vitamin B7, is a water-soluble vitamin. It has multiple roles in fat, carbohydrate metabolism, cell growth and protein synthesis in body. Of late, several formulations either cosmetic or food include vitamin B7 with a focus on hair and nail health. Although research on direct effect of biotin on hair growth is limited, several reports of clinical success do exist, which show

improvement in hair and nail health upon biotin supplementation in individuals with hair and nail pathology, like uncombable hair and brittle nail (Patel et al., 2017, Skin Appendage Disorder. Review. 3(3): 166-169).
[0036] In an embodiment of the present disclosure, there is provided a composition comprising: a) naringenin; b) genistein; c) coenzyme Q10; and d) biotin, wherein naringenin to genistein to coenzyme Q10 weight ratio in said composition is in a range of 0.75-1.25: 0.75-1.25: 0.75-1.25. In another embodiment of the present disclosure, the naringenin to genistein to coenzyme Q10 weight ratio in said composition is in the range of 0.9-1.1:0.9:1.1:0.9-1.1. In yet another embodiment of the present disclosure, the naringenin to genistein to coenzyme Q10 weight ratio in said composition is 1:1:1.
[0037] In an embodiment of the present disclosure, there is provided a composition as described herein, wherein naringenin to genistein to coenzyme Q10 to biotin weight ratio in said composition is in a range of 0.75-1.25: 0.75-1.25: 0.75-1.25: 0.002-0.3. In another embodiment of the present disclosure, naringenin to genistein to coenzyme Q10 to biotin weight ratio in said composition is in the range of 0.9-1.1:0.9:1.1:0.9-1.1:0.0022:0.1 In yet another embodiment of the present disclosure, naringenin to genistein to coenzyme Q10 to biotin weight ratio in said composition is 1:1:1:0.0022. In yet another embodiment of the present disclosure, naringenin to genistein to coenzyme Q10 to biotin weight ratio in said composition is 1:1:1:0.1. [0038] In an embodiment of the present disclosure, there is provided a composition comprising: a) naringenin; b) genistein; c) coenzyme Q10; and d) biotin, wherein naringenin to genistein to coenzyme Q10 to biotin weight ratio in said composition is in a range of 0.75-1.25: 0.75-1.25: 0.75-1.25: 0.002-0.3.
[0039] In another embodiment of the present disclosure, there is provided a composition as described herein, wherein naringenin has a weight percentage in a range of 0.3%-0.6% with respect to the composition, genistein has a weight percentage in a range of 0.3%-0.6% with respect to the composition, coenzyme Q10 has weight percentage in the range of 0.3%-0.6% with respect to the composition, and biotin has a weight percentage in a range of 0.0007%-0.1% with respect to the composition. In another embodiment of the present disclosure,

naringenin has a weight percentage in the range of 0.4 - 0.5% with respect to the composition, genistein has a weight percentage in the range of 0.4 - 0.5% with respect to the composition, coenzyme Q10 has a weight percentage in the range of 0.4 - 0.5%) with respect to the composition, and biotin has a weight percentage in the range of 0.0022 - 0.1%> with respect to the composition. In yet another embodiment of the present disclosure, naringenin has a weight percentage of 0.45% with respect to the composition, genistein has a weight percentage of 0.45% with respect to the composition, coenzyme Q10 has a weight percentage of 0.45% with respect to the composition, and biotin has a weight percentage of 0.001% with respect to the composition.
[0040] In another embodiment of the present disclosure, there is provided a composition comprising: a) naringenin; b) genistein; c) coenzyme Q10; and d) biotin, wherein naringenin to genistein to coenzyme Q10 weight ratio in said composition is in a range of 0.75-1.25: 0.75-1.25: 0.75-1.25; and wherein naringenin has a weight percentage in a range of 0.3%-0.6% with respect to the composition, genistein has a weight percentage in a range of 0.3%-0.6% with respect to the composition, coenzyme Q10 has weight percentage in the range of 0.3%-0.6%with respect to the composition, and biotin has a weight percentage in a range of 0.0007%-0.1% with respect to the composition.
[0041] In another embodiment of the present disclosure, there is provided a composition comprising: a) naringenin; b) genistein; c) coenzyme Q10; and d) biotin, wherein naringenin to genistein to coenzyme Q10 to biotin weight ratio in said composition is in a range of 0.75-1.25: 0.75-1.25: 0.75-1.25: 0.002-0.3; and wherein naringenin has a weight percentage in a range of 0.3%-0.6% with respect to the composition, genistein has a weight percentage in a range of 0.3%-0.6% with respect to the composition, coenzyme Q10 has weight percentage in the range of 0.3%-0.6% with respect to the composition, and biotin has a weight percentage in a range of 0.0007%-0.1% with respect to the composition.
[0042] In another embodiment of the present disclosure, there is provided a composition comprising: a) naringenin; b) genistein; c) coenzyme Q10; and d) biotin, wherein naringenin to genistein to coenzyme Q10 to biotin weight ratio in

said composition is 1:1:1:0.002; and wherein naringenin has a weight percentage of 0.45% with respect to the composition, genistein has a weight percentage of 0.45% with respect to the composition, coenzyme Q10 has a weight percentage of 0.45% with respect to the composition, and biotin has a weight percentage of 0.001% with respect to the composition.
[0043] In another embodiment of the present disclosure, there is provided a composition as described herein, wherein the composition further comprises at least one carrier selected from a group consisting of thickener, humectant, emulsifier, hair oil, neutralizer, soothing agent, preservative, revitalizing agent, conditioning agent, the moisturizing agent, antidandruff agent, hair cell stimulator, diluent, silicone oil, antioxidant, and combinations thereof. In an embodiment, the thickener is a carbomer; the humectant is glycerine; the emulsifier is at least one of polysorbate - 20, microcrystalline wax, ceteareth-20, cetearyl alcohol, and combinations thereof; the hair oil is coconut oil; the silicone oil is polydimethyl siloxane polymer; the antioxidant is at least one of naringenin, genistein, coenzyme Q10, and combinations thereof; the neutralizer is triethanolamine; the soothing agent is allantoin; the preservative is phenoxyethanol, methylparaben, ethylparaben, n-butylparaben, isobutylparaben, and combinations thereof; the antidandruff agent is climbazole; the conditioning agent is PEG - 12 dimethicone; the revitalizing agent is magnesium aspartate, zinc gluconate, copper gluconate; the hair cell stimulator is caffeine, biotin, and combinations thereof; the moisturizing agent is D-panthenol; and the diluent is water.
[0044] In an embodiment of the present disclosure, there is provided a composition comprising: a) naringenin; b) genistein; c) coenzyme Q10; and d) biotin, wherein naringenin to genistein to coenzyme Q10 weight ratio in said composition is in a range of 0.75-1.25: 0.75-1.25: 0.75-1.25; and wherein the composition further comprises at least one carrier selected from a group consisting of thickener, humectant, emulsifier, hair oil, neutralizer, soothing agent, preservative, revitalizing agent, conditioning agent, the moisturizing agent, antidandruff agent, hair cell stimulator, diluent, and combinations thereof.

[0045] In an embodiment of the present disclosure, there is provided a composition comprising: a) naringenin; b) genistein; c) coenzyme Q10; and d) biotin, wherein naringenin to genistein to coenzyme Q10 to biotin weight ratio in said composition is in a range of 0.75-1.25: 0.75-1.25: 0.75-1.25: 0.002-0.3; and wherein the composition further comprises at least one carrier selected from a group consisting of thickener, humectant, emulsifier, hair oil, neutralizer, soothing agent, preservative, revitalizing agent, conditioning agent, the moisturizing agent, antidandruff agent, hair cell stimulator, diluent, and combinations thereof. [0046] In an embodiment of the present disclosure, there is provided a composition comprising: a) naringenin; b) genistein; c) coenzyme Q10; and d) biotin, wherein naringenin to genistein to coenzyme Q10 weight ratio in said composition is 1:1:1; and wherein the composition further comprises at least one carrier selected from a group consisting of thickener, humectant, emulsifier, hair oil, neutralizer, soothing agent, preservative, revitalizing agent, conditioning agent, the moisturizing agent, antidandruff agent, hair cell stimulator, diluent, and combinations thereof. [0047] In an embodiment of the present disclosure, there is provided a composition as described herein, wherein the composition further comprises at least one carrier selected from a group consisting of thickener, humectant, emulsifier, hair oil, neutralizer, soothing agent, preservative, revitalizing agent, conditioning agent, the moisturizing agent, antidandruff agent, hair cell stimulator, diluent, and combinations thereof, and wherein the thickener has a weight percentage in a range of 0.1-0.2% with respect to the composition, the humectant has a weight percentage in a range of 0.5-2% with respect to the composition, the emulsifier has a weight percentage in a range of 4-8% with respect to the composition, the hair oil has a weight percentage in a range of 8-12% with respect to the composition, the silicone oil has a weight percentage in a range of 4 - 6%> with respect to the composition; the antioxidants have a weight percentage of 1 - 2% with respect to the composition; the neutralizer has a weight percentage in a range of 0.05-0.2%) with respect to the composition, the soothing agent has a weight percentage in a range of 0.05-0.2%) with respect to the composition, the preservative has a weight percentage in a range of 0.3-1% with respect to the composition, the revitalizing

agent has a weight percentage in a range of 0.05-0.2% with respect to the composition, the conditioning agent has a weight percentage in a range of 3-10% with respect to the composition, the antidandruff agent has a weight percentage in a range of 0.3-1% with respect to the composition, the hair cell stimulator has a weight percentage in a range of 0.5-2% with respect to the composition, the moisturizing agent has a weight percentage in a range of 0.05-0.2%) with respect to the composition, and the diluent has a weight percentage in a range of 65-75%> with respect to the composition. In another embodiment of the present disclosure, thickener has a weight percentage in a range of 0.14-0.16%) with respect to the composition, the humectant has a weight percentage in a range of 0.75-1.25%) with respect to the composition, the emulsifier has a weight percentage in a range of 5-7%o with respect to the composition, the hair oil has a weight percentage in a range of 9-ll%o with respect to the composition, the silicone oil has a weight percentage in a range of 4 - 6%> with respect to the composition; the antioxidants have a weight percentage of 1.3 - 1.5% with respect to the composition; the neutralizer has a weight percentage in a range of 0.75-0.2%) with respect to the composition, the soothing agent has a weight percentage in a range of 0.75-0.2%) with respect to the composition, the preservative has a weight percentage in a range of 0.4-0.6%) with respect to the composition, the revitalizing agent has a weight percentage in a range of 0.05-0.15%) with respect to the composition, the conditioning agent has a weight percentage in a range of 4-6%> with respect to the composition, the antidandruff agent has a weight percentage in a range of 0.4-0.6%) with respect to the composition, the hair cell stimulator has a weight percentage in a range of 0.5-1.5% with respect to the composition, the moisturizing agent has a weight percentage in a range of 0.09-0.15%) with respect to the composition, and the diluent has a weight percentage in a range of 68-72%> with respect to the composition.
[0048] In an embodiment of the present disclosure, there is provided a composition comprising: a) naringenin; b) genistein; c) coenzyme Q10; d) biotin; and e) at least one carrier selected from a group consisting of thickener, humectant, emulsifier, hair oil, neutralizer, soothing agent, preservative, revitalizing agent, conditioning

agent, the moisturizing agent, antidandruff agent, hair cell stimulator, diluent, and combinations thereof, wherein naringenin to genistein to coenzyme Q10 weight ratio in said composition is 0.75-1.25: 0.75-1.25: 0.75-1.25; and wherein naringenin has a weight percentage in a range of 0.3%-0.6% with respect to the composition, genistein has a weight percentage in a range of 0.3%-0.6% with respect to the composition, coenzyme Q10 has weight percentage in the range of 0.3%-0.6% with respect to the composition, and biotin has a weight percentage in a range of 0.0007%-0.1% with respect to the composition; and wherein the thickener has a weight percentage in a range of 0.1-0.2% with respect to the composition, the humectant has a weight percentage in a range of 0.5-2% with respect to the composition, the emulsifier has a weight percentage in a range of 4-8% with respect to the composition, the hair oil has a weight percentage in a range of 8-12% with respect to the composition, the silicone oil has a weight percentage in a range of 4 - 6%> with respect to the composition; the antioxidants have a weight percentage of 1 - 2% with respect to the composition; the neutralizer has a weight percentage in a range of 0.05-0.2%) with respect to the composition, the soothing agent has a weight percentage in a range of 0.05-0.2%) with respect to the composition, the preservative has a weight percentage in a range of 0.3-1% with respect to the composition, the revitalizing agent has a weight percentage in a range of 0.05-0.2%) with respect to the composition, the conditioning agent has a weight percentage in a range of 3-10% with respect to the composition, the antidandruff agent has a weight percentage in a range of 0.3-1% with respect to the composition, the hair cell stimulator has a weight percentage in a range of 0.5-2% with respect to the composition, the moisturizing agent has a weight percentage in a range of 0.05-0.2%) with respect to the composition, and the diluent has a weight percentage in a range of 65-75%> with respect to the composition.
[0049] In an embodiment of the present disclosure, there is provided a composition comprising: a) naringenin; b) genistein; c) coenzyme Q10; and d) biotin, wherein naringenin to genistein to coenzyme Q10 to biotin weight ratio in said composition is in a range of 0.75-1.25: 0.75-1.25: 0.75-1.25: 0.002-0.3; and wherein naringenin has a weight percentage in a range of 0.3%-0.6% with respect to the composition,

genistein has a weight percentage in a range of 0.3%-0.6% with respect to the composition, coenzyme Q10 has weight percentage in the range of 0.3%-0.6% with respect to the composition, and biotin has a weight percentage in a range of 0.0007%-0.1% with respect to the composition; and wherein the thickener has a weight percentage in a range of 0.1-0.2% with respect to the composition, the humectant has a weight percentage in a range of 0.5-2% with respect to the composition, the emulsifier has a weight percentage in a range of 4-8% with respect to the composition, the hair oil has a weight percentage in a range of 8-12% with respect to the composition, the silicone oil has a weight percentage in a range of 4 - 6%> with respect to the composition; the antioxidants have a weight percentage of 1 - 2% with respect to the composition; the neutralizer has a weight percentage in a range of 0.05-0.2%) with respect to the composition, the soothing agent has a weight percentage in a range of 0.05-0.2%) with respect to the composition, the preservative has a weight percentage in a range of 0.3-1% with respect to the composition, the revitalizing agent has a weight percentage in a range of 0.05-0.2%) with respect to the composition, the conditioning agent has a weight percentage in a range of 3-10% with respect to the composition, the antidandruff agent has a weight percentage in a range of 0.3-1% with respect to the composition, the hair cell stimulator has a weight percentage in a range of 0.5-2% with respect to the composition, the moisturizing agent has a weight percentage in a range of 0.05-0.2%) with respect to the composition, and the diluent has a weight percentage in a range of 65-75%> with respect to the composition.
[0050] In an embodiment of the present disclosure, there is provided a process for preparing a composition comprising: a) naringenin; b) genistein; c) coenzyme Q10; and d) biotin, wherein naringenin to genistein to coenzyme Q10 weight ratio in said composition is in a range of 0.75-1.25: 0.75-1.25: 0.75-1.25; said process comprising: i) obtaining naringenin; ii) obtaining genistein; iii) obtaining coenzyme Q10; iv) obtaining biotin; and v) contacting naringenin, genistein, coenzyme Q10, and biotin to obtain the composition.
[0051] In an embodiment of the present disclosure, there is provided a process for preparing a composition comprising: a) naringenin; b) genistein; c) coenzyme Q10;

and d) biotin, naringenin to genistein to coenzyme Q10 to biotin weight ratio in said composition is in a range of 0.75-1.25: 0.75-1.25: 0.75-1.25: 0.002-0.3; said process comprising: i) obtaining naringenin; ii) obtaining genistein; iii) obtaining coenzyme Q10; iv) obtaining biotin; and v) contacting naringenin, genistein, coenzyme Q10, and biotin to obtain the composition.
[0052] In an embodiment of the present disclosure, there is provided a process for preparing a composition comprising: a) naringenin; b) genistein; c) coenzyme Q10; and d) biotin, wherein naringenin to genistein to coenzyme Q10 to biotin weight ratio in said composition is in a range of 0.75-1.25: 0.75-1.25: 0.75-1.25: 0.002-0.3; and wherein naringenin has a weight percentage in a range of 0.3%-0.6% with respect to the composition, genistein has a weight percentage in a range of 0.3%-0.6% with respect to the composition, coenzyme Q10 has weight percentage in the range of 0.3%-0.6% with respect to the composition, and biotin has a weight percentage in a range of 0.0007%-0.1% with respect to the composition; and wherein the thickener has a weight percentage in a range of 0.1-0.2%) with respect to the composition, the humectant has a weight percentage in a range of 0.5-2% with respect to the composition, the emulsifier has a weight percentage in a range of 4-8%) with respect to the composition, the hair oil has a weight percentage in a range of 8-12% with respect to the composition, the silicone oil has a weight percentage in a range of 4 - 6%> with respect to the composition; the antioxidants have a weight percentage of 1 - 2% with respect to the composition; the neutralizer has a weight percentage in a range of 0.05-0.2%) with respect to the composition, the soothing agent has a weight percentage in a range of 0.05-0.2%) with respect to the composition, the preservative has a weight percentage in a range of 0.3-1% with respect to the composition, the revitalizing agent has a weight percentage in a range of 0.05-0.2%) with respect to the composition, the conditioning agent has a weight percentage in a range of 3-10% with respect to the composition, the antidandruff agent has a weight percentage in a range of 0.3-1% with respect to the composition, the hair cell stimulator has a weight percentage in a range of 0.5-2% with respect to the composition, the moisturizing agent has a weight percentage in a range of 0.05-0.2%) with respect to the composition, and the diluent has a weight

percentage in a range of 65-75% with respect to the composition; said process comprising: i) obtaining naringenin; ii) obtaining genistein; iii) obtaining coenzyme Q10; iv) obtaining biotin; and v) contacting naringenin, genistein, coenzyme Q10, and biotin to obtain the composition.
[0053] In an embodiment of the present disclosure, there is provided a process for preparing a composition comprising: a) naringenin; b) genistein; c) coenzyme Q10; d) biotin; and e) at least one carrier, wherein naringenin to genistein to coenzyme Q10 weight ratio in said composition is in a range of 0.75-1.25: 0.75-1.25: 0.75-1.25; said process comprising: i) obtaining naringenin; ii) obtaining genistein; iii) obtaining coenzyme Q10; iv) obtaining biotin; v) obtaining at least one carrier; and vi) contacting naringenin, genistein, coenzyme Q10, biotin; and the at least one carrier to obtain the composition.
[0054] In an embodiment of the present disclosure, there is provided a process for preparing a composition comprising: a) naringenin; b) genistein; c) coenzyme Q10; d) biotin; and e) at least one carrier, wherein naringenin to genistein to coenzyme Q10 weight ratio in said composition is in a range of 0.75-1.25: 0.75-1.25: 0.75-1.25: 0.002-0.3; said process comprising: i) obtaining naringenin; ii) obtaining genistein; iii) obtaining coenzyme Q10; iv) obtaining biotin; v) obtaining at least one carrier; and vi) contacting naringenin, genistein, coenzyme Q10, biotin; and the at least one carrier to obtain the composition.
[0055] In an embodiment of the present disclosure, there is provided a process for preparing a composition comprising: a) naringenin; b) genistein; c) coenzyme Q10; d) biotin; and e) at least one carrier selected from a group consisting of thickener, humectant, emulsifier, hair oil, neutralizer, soothing agent, preservative, revitalizing agent, conditioning agent, the moisturizing agent, antidandruff agent, hair cell stimulator, diluent, and combinations thereof, wherein naringenin to genistein to coenzyme Q10 to biotin weight ratio in said composition is in a range of 0.75-1.25: 0.75-1.25: 0.75-1.25: 0.002-0.3, and wherein naringenin has a weight percentage in a range of 0.3%-0.6% with respect to the composition, genistein has a weight percentage in a range of 0.3%-0.6% with respect to the composition, coenzyme Q10 has weight percentage in the range of 0.3%-0.6%with respect to the

composition, and biotin has a weight percentage in a range of 0.0007%-0.1% with respect to the composition; and wherein the thickener has a weight percentage in a range of 0.1-0.2% with respect to the composition, the humectant has a weight percentage in a range of 0.5-2% with respect to the composition, the emulsifier has a weight percentage in a range of 4-8% with respect to the composition, the hair oil has a weight percentage in a range of 8-12% with respect to the composition, the silicone oil has a weight percentage in a range of 4 - 6%> with respect to the composition; the antioxidants have a weight percentage of 1 - 2% with respect to the composition; the neutralizer has a weight percentage in a range of 0.05-0.2%) with respect to the composition, the soothing agent has a weight percentage in a range of 0.05-0.2%) with respect to the composition, the preservative has a weight percentage in a range of 0.3-1% with respect to the composition, the revitalizing agent has a weight percentage in a range of 0.05-0.2%) with respect to the composition, the conditioning agent has a weight percentage in a range of 3-10% with respect to the composition, the antidandruff agent has a weight percentage in a range of 0.3-1% with respect to the composition, the hair cell stimulator has a weight percentage in a range of 0.5-2% with respect to the composition, the moisturizing agent has a weight percentage in a range of 0.05-0.2%) with respect to the composition, and the diluent has a weight percentage in a range of 65-75%> with respect to the composition; said process comprising: i) obtaining naringenin; ii) obtaining genistein; iii) obtaining coenzyme Q10; iv) obtaining biotin; v) obtaining at least one carrier; and vi) contacting naringenin, genistein, coenzyme Q10, biotin; and the at least one carrier to obtain the composition.
[0056] In an embodiment of the present disclosure, there is provided a composition as descried herein, wherein the composition inhibits IL-4 expression. [0057] In an embodiment of the present disclosure, there is provided a composition as descried herein, wherein the composition leads to hair growth. [0058] In an embodiment of the present disclosure, there is provided a composition as descried herein, wherein the composition is in a form of serum. [0059] In an embodiment of the present disclosure, there is provided a composition as descried herein, wherein the composition is in a form of oil.

[0060] In an embodiment of the present disclosure, there is provided a composition as descried herein, wherein the composition is in a form of cream. [0061] 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
[0062] 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. [0063] The working examples described herein clearly depict the effect of the composition of the present disclosure on interleukin (TL) - 4 gene expression. The present disclosure is directed to a composition comprising naringenin, genistein, biotin, and coenzyme Q10, which when used in defined w/w ratio's is effective in inhibiting IL-4 production, and consequently lower the induction of apoptosis in follicular keratinocytes that responsible for hair and nail growth. Materials and Methods
[0064] The ingredients naringenin, genistein, and coenzyme Q10 were procured from Biogen Idee Biotech, Pvt. Ltd. India. Biotin was procured from Sigma. Example 1: RNA extraction and Real-time PCR

[0065] For this purpose, HaCaaT cells were seeded onto a 12-well plate at a density of 1 x 105 cells/ well and incubated at 37°C with 5% C02, for about 24 hours (till 70-80% confluency is reached). The cells were then treated with actives in at individual concentration as well as in combinations of different w/w ratios. The cells were simultaneously treated with different combinations of both the actives and incubated at 37°C, with 5% CO2 for 24 hours. Post incubation, the media from the wells were discarded, and the cells were washed with 1ml of lx phosphate buffer saline (PBS) followed by addition of 1 ml of trizol reagent (Ambion, Life Technologies, USA) in each well. The plate was incubated at -80°C overnight and RNA isolation was performed next day in the same trizol reagent. The steps followed for the RNA isolation were as per the manufacturer's protocol (Ambion, Life Technologies, USA). The resulting RNA was quantified using TECAN, Infinite M200 Pro, USA, a multimode microplate reader. cDNA was synthesized from the RNA, using High Capacity cDNA reverse transcription kit 200 reactions (Applied Biosystems, USA). The expression levels of target gene, IL-4 was determined by real time PCR using ABI7500 Real Time PCR system from Applied Biosystems USA. GAPDH was used as endogenous control for the present study. The sequences of the primers are given in table 2 below:
The PCR program was as follows: (a) preheating for 2 minutes at 50°C and heating for 10 minutes at 95°C (b) 40 cycles of denaturation, annealing and extension at 95°C for 15 seconds and 60°C for 1 minute (c) melting curve analysis at 95°C for 15 seconds, 60°C for 1 minute, 95 °C for 30 seconds and 60 °C for 15 seconds. The expression levels of IL-4 genes were normalized to GAPDH gene expression in each sample. Example 2: Formulation

[0066] Two different formulations were prepared in which all the ingredients, were combined in different fractions, as provided below in Table 3.
Example 3: Process of preparation of the formulation
[0067] The formulations Al and A2 as disclosed in example 2, were prepared by
mixing all the constituents as disclosed in Example 4, namely naringenin,

genistein, coenzyme Q10, biotin, and obtaining carriers comprising carbomer, glycerine, polysorbate 20, coconut oil, microcrystalline wax, polydimethyl siloxane polymer, ceteareth-20, cetearyl alcohol, triethanolamine, allantoin, phenoxyethanol, methylparaben, ethyl paraben, n-butylparaben, isobutyl paraben, magnesium aspartate, zinc gluconate, copper gluconate, PEG-12 dimethicone, climbazole, caffeine, D-panthenol, and water, at a temperature range of 25 - 27 °C to obtain the composition
RESULTS AND DISCUSSION
Evaluating the effect of the composition on Interleukin (IL)-4 gene expression [0068] To evaluate the effect of the biotin in the composition on IL-4 gene expression, compositions with and without biotin at defined w/w ratio was exposed to HaCaat cells. The experiment was carried out as per the procedure detailed in Example 1. The results of this study are presented in Figure 1. DMSO was used as a control. The term 'N', 'G', 'C and 'B' used in the figures correspond to naringenin, genistein, coenzyme Q10 and biotin, respectively. The percentage reduction in IL-4 gene expression was found to be around 10% with 0.001% of biotin; whereas 60% reduction was observed with a combination of actives (naringenin, genistein, and coenzyme Q10 at w/w ratio 1:1:1). However, unexpectedly and surprisingly, the percentage reduction in IL-4 was found to be around 71% when a combination of naringenin, genistein, coenzyme Q10 and biotin at w/w ratio of 1:1:1:0.001 was used, which is greater than the percentage reduction with biotin alone or with a combination of naringenin, genistein, and coenzyme Q10 alone. This suggests that naringenin, genistein, coenzyme Q10 and biotin at w/w ratio of 1:1:1:0.001 shows a synergistic inhibition of IL-4. In other words, the IL-4 level analysis shows that there is reduced IL-4 expression with naringenin, genistein, coenzyme Q10 and biotin at w/w ratio 1:1:1:0.001, suggesting that the apoptosis induction is lower compared to that induced by a combination of naringenin, genistein, and coenzyme Q10 at w/w ratio of 1:1:1. For the experimentation purpose, composition comprising naringenin, genistein, coenzyme Q10, and/or biotin (as per the study) was used. The carrier components were not used for the experimentation aspect.

[0069] Based on the results observed in Figure 1, the experiment was repeated at varying w/w ratios and their effect of percentage reduction in IL-4 was observed. The results are herewith presented below in Table 4, and Figure 2.
[0070] As can be seen in Table 4, and Figure 2, for the various w/w ratios of naringenin, genistein, coenzyme Q10, and biotin tested, it can be observed that a synergistic inhibition in IL-4 expression levels in found to be at w/w ratio 1:1:1:0.001. The IL-4 expression level was found to be higher for all the other ratios tested. This data suggests that the particular w/w ratio 1:1:1:0.001 has the least potential to induce apoptosis, and consequently offer great benefits for hair growth applications.
Advantages of the present disclosure:
[0071] The present disclosure reveals a composition comprising a) naringenin; b) genistein; c) coenzyme Q10; and d) biotin, wherein naringenin to genistein to coenzyme Q10 weight ratio in said composition is in a range of 0.75-1.25: 0.75-1.25: 0.75-1.25. The composition of the present disclosure can be effectively deployed in the cosmetic industry as it reduces interleukin (IL)-4 gene expression; and consequently, lower the induction of apoptosis in follicular keratinocytes, thereby promoting hair and nail growth. Further, the compositions used are safe for application, and the actives being non-synthetic components, the chances of any side effects is also minimized.

I/We Claim:
1. A composition comprising:
(a) naringenin;
(b) genistein;
(c) coenzyme Q10; and
(d) biotin,
wherein naringenin to genistein to coenzyme Q10 weight ratio in said composition is in a range of 0.75-1.25: 0.75-1.25: 0.75-1.25.
2. The composition as claimed in claim 1, wherein naringenin to genistein to coenzyme Q10 to biotin weight ratio in said composition is in a range of 0.75-1.25: 0.75-1.25: 0.75-1.25: 0.002-0.3.
3. The composition as claimed in claim 1, wherein naringenin to genistein to coenzyme Q weight ratio in said composition is 1:1:1.
4. The composition as claimed in claim 1, wherein naringenin has a weight percentage in a range of 0.3%-0.6% with respect to the composition, genistein has a weight percentage in a range of 0.3%-0.6% with respect to the composition, coenzyme Q10 has weight percentage in the range of 0.3-0.6% with respect to the composition, and biotin has a weight percentage in a range of 0.0007%-0.1% with respect to the composition.
5. The composition as claimed in claim 4, wherein naringenin has a weight percentage of 0.45% with respect to the composition, genistein has a weight percentage of 0.45% with respect to the composition, coenzyme Q10 has a weight percentage of 0.45% with respect to the composition, and biotin has a weight percentage of 0.001% with respect to the composition.
6. The composition as claimed in any one of the claims 1-5, wherein the composition further comprises at least one carrier selected from a group consisting of thickener, humectant, emulsifier, hair oil, neutralizer, soothing agent, preservative, revitalizing agent, conditioning agent, silicone oil, antioxidant, moisturizing agent, antidandruff agent, hair cell stimulator, diluent, and combinations thereof.

7. The composition as claimed in claim 6, wherein the thickener has a weight percentage in a range of 0.1-0.2% with respect to the composition, the humectant has a weight percentage in a range of 0.5-2% with respect to the composition, the emulsifier has a weight percentage in a range of 4-8% with respect to the composition, the hair oil has a weight percentage in a range of 8-12%) with respect to the composition, the silicone oil having a weight percentage in a range of 4-6%> with respect to the composition; the antioxidant having a weight percentage in a range of 1 - 2% with respect to the composition; the neutralizer has a weight percentage in a range of 0.05-0.2%) with respect to the composition, the soothing agent has a weight percentage in a range of 0.05-0.2%) with respect to the composition, the preservative has a weight percentage in a range of 0.3-1 % with respect to the composition, the revitalizing agent has a weight percentage in a range of 0.05-0.2%) with respect to the composition, the conditioning agent has a weight percentage in a range of 3-10% with respect to the composition, the antidandruff agent has a weight percentage in a range of 0.3-1% with respect to the composition, the hair cell stimulator has a weight percentage in a range of 0.5-2%) with respect to the composition, the moisturizing agent has a weight percentage in a range of 0.05-0.2%) with respect to the composition, and the diluent has a weight percentage in a range of 65-75%> with respect to the composition.
8. A method to prepare the composition as claimed in claim 1, said method comprising:

(a) obtaining naringenin;
(b) obtaining geni stein;
(c) obtaining coenzyme Q10;
(d) obtaining biotin; and
(e) contacting naringenin, genistein, coenzyme Q10, and biotin to obtain the composition.
9. A method to prepare the composition as claimed in claim 6, said method
comprising:

(a) obtaining naringenin;
(b) obtaining geni stein;
(c) obtaining coenzyme Q10;
(d) obtaining biotin;
(e) obtaining the at least one carrier; and
(f) contacting naringenin, genistein, coenzyme Q10, biotin, and the at least one carrier to obtain the composition.
10. The composition as claimed in any one of the claims 1-7, wherein the composition inhibits IL-4 expression.