DESC:FIELD OF INVENTION
[0001] The present disclosure relates to the field of pharmaceutical compositions. In particular, the present disclosure relates to a safe and optimized pharmaceutical composition that may find utility in treatment, prevention and amelioration of hirsutism. It further relates to a process of preparing the pharmaceutical composition.

BACKGROUND OF THE INVENTION
[0002] Background description includes information that may be useful in understanding the present invention. It is not an admission that any of the information provided herein is prior art or relevant to the present invention, or that any publication specifically or implicitly referenced is prior art.
[0003] Hirsutism is a condition in women characterized by existence of excessive growth of coarse hair that follows a male-like pattern in androgen-dependent areas in females. These androgen-dependent areas include the chin, upper lip, chest, lower abdomen, thighs or back. It affects 5-15% women with the presence of large, coarse, facial terminal hairs. The underlying cause of hirsutism includes an increased level of male hormone (androgens), primarily testosterone. Testosterone is converted into the more active form called Dihydrotestosterone (DHT) which is mediated by the enzyme 5-alphareductase. Testosterone when readily converted into DHT, acts on the hair follicles to produce terminal hair. Thus, in hirsutism, it is the active intermediary-DHT which triggers excessive terminal hair growth with prolonged anagen phase (growing phase), wherein the cells at the root of hair multiply at a rapid rate. It is also characterized by increase in hair follicle size, hair follicle diameter and sebum secretion.
[0004] Treatments are available in the market for hirsutism including cosmetic treatments and/or medications. Cosmetic treatment includes waxing, shaving, depilation and laser hair reduction. These are not permanent solutions and need to be performed repeatedly. Medications for the treatment include anti-androgenic compounds, oral contraceptives, or receptor agonists like Eflornithine (Vaniqa). Significant efforts have been put forward towards finding new and improved compositions, however, none of the current approaches/treatments seems to satisfy the existing needs, and are either proved ineffective or lead to serious long term side-effects.
[0005] There is, therefore, an unmet need in the art to develop a new and improved pharmaceutical composition for effectively treating hirsutism without causing any side-effects. The present disclosure fulfils the existing needs, at least in part, and alleviates one or more shortcomings of the conventional compositions.

OBJECTS OF THE INVENTION
[0006] An object of the present disclosure is to provide a pharmaceutical composition for effective management of hirsutism comprising natural components.
[0007] It is an object of the present disclosure to provide a composition that is substantially devoid of any side-effects.
[0008] It is an object of the invention to provide a composition that exhibits superior storage stability and synergistic activity /functional reciprocity.
[0009] It is an object of the invention to provide a composition that is easy to prepare and economical.
[00010] It is an object of the present disclosure to provide a composition that decreases the proliferation of human dermal papilla cells (HFDPCs).
[00011] It is an object of the present disclosure to provide a process of preparing a pharmaceutical composition for management of hirsutism.
[00012] Other objects of the present disclosure will be apparent from the description of the invention herein below.

SUMMARY
[00013] This summary is provided to introduce a selection of concepts in a simplified form that are further described below in detailed description section. This summary is not intended to identify key features or essential features of the subject matter, nor is it intended to be used as an aid in determining the scope of the subject matter.
[00014] The present disclosure relates to the field of pharmaceutical composition. In particular, the present disclosure relates to a safe and optimized pharmaceutical composition that may find utility in treatment, prevention and amelioration of hirsutism. It further relates to a process of preparing the pharmaceutical composition.
[00015] In an aspect, the present disclosure provides a pharmaceutical composition for management of hirsutism comprising curcumin in a range of about 0.01% w/w to about 5% w/w, Cyperus rotundus in a range of about 0.01% w/w to about 5% w/w, green tea in a range of about 2% w/w to about 45% w/w, soya protein in a range of about 30% w/w to about 60% w/w; natural oils in a range of about 0.1% w/w to about 5% w/w; Hamamelis in a range of about 0.01% w/w to about 5% w/w; and one or more pharmaceutically acceptable excipient(s) in a range of about 0.1% w/w to about 20% w/w.
[00016] In an embodiment, the natural oils may be selected from fenugreek oil, almond oil, turmeric oil, sunflower oil, spearmint oil, castor oil, basil oil, coconut oil, olive oil, lavender oil, or combinations thereof.
[00017] In an embodiment, the composition comprises curcumin in about 0.1% w/w to about 0.5% w/w, extract of Cyperus rotundus in about 0.1% w/w to about 0.5% w/w, extract of green tea in about 30% w/w to about 40% w/w, soya protein in about 50% w/w to about 60% w/w, natural oils in about 1% w/w to about 3% w/w, extract of Hamamelis in about 0.1% w/w to about 2% w/w and one or more pharmaceutically acceptable excipient(s) in about 5% w/w to about 15% w/w.
[00018] In an embodiment, the composition may further comprise a solvent.
[00019] In an aspect, the present disclosure provides a pharmaceutical cream formulation for management of hirsutism comprising curcumin in a range of about 0.01% w/w to about 5% w/w, Cyperus rotundus in a range of about 0.01% w/w to about 5% w/w, green tea in a range of about 2% w/w to about 45% w/w, soya protein in a range of about 30% w/w to about 60% w/w; natural oils in a range of about 0.1% w/w to about 5% w/w; Hamamelis in a range of about 0.01% w/w to about 5% w/w; and one or more pharmaceutically acceptable excipient(s) in a range of about 0.1% w/w to about 20% w/w.
[00020] In another aspect, the present disclosure relates to a process of preparing a pharmaceutical composition comprising the steps of: (a) taking flocare and dissolving it in water for base; (b) dissolving basil oil, menthol, and DMDM hydantoin in the base with continuous stirring; (c) taking soya protein, curcumin, green tea, sodium acrylate/sodium acryloyl dimethyl taurate copolymer and Cyprus rotundus in a separate container and dissolving them in water; (d) mixing the solution of step (c) and step (b); (e) preparing organic phase by taking castor oil, spearmint oil, sunflower oil, almond oil, camphor, turmeric oil, fenugreek oil, Hamamelis extract and allantoin and heating at about 50-70 ºC till clear solution is obtained; and (f) mixing the solution of step (d) and the organic phase of step (e) to give the formulation.
[00021] In another aspect, the present disclosure provides a method for treatment of hirsutism in a subject by administering a therapeutically effective amount of a composition or formulation as recited herein above.
[00022] Other aspects of the invention will be set forth in the description which follows, and in part will be apparent from the description, or may be learnt by the practice of the invention.

DETAILED DESCRIPTION OF THE INVENTION
[00023] The embodiments herein and the various features and advantageous details thereof are explained more comprehensively with reference to the non-limiting embodiments that are detailed in the following description. Descriptions of well-known components and processing techniques are omitted to not unnecessarily obscure the embodiments herein. The examples used herein are intended merely to facilitate an understanding of the ways in which the embodiments herein may be practiced and to further enable those of skill in the art to practice the embodiments herein. Accordingly, the examples should not be construed as limiting the scope of the embodiments herein.
[00024] Unless otherwise specified, all terms used in disclosing the invention, including technical and scientific terms, have the meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. By means of further guidance, term definitions may be included to better appreciate the teaching of the present invention.
[00025] As used in the description herein, the meaning of “a,” “an,” and “the” includes plural reference unless the context clearly dictates otherwise. Also, as used in the description herein, the meaning of “in” includes “in” and “on” unless the context clearly dictates otherwise.
[00026] As used herein, the terms “comprise”, “comprises”, “comprising”, “include”, “includes”, and “including” are meant to be non- limiting, i.e., other steps and other ingredients which do not affect the end of result can be added. The above terms encompass the terms “consisting of” and “consisting essentially of”.
[00027] As used herein, the terms “composition”, “blend”, or “mixture” are all intended to be used interchangeably.
[00028] The terms “weight percent”, “vol-%”, “percent by weight”, “% by weight”, and variations thereof, as used herein, refer to the concentration of a substance as the weight of that substance divided by the total weight of the composition and multiplied by 100. It is understood that, as used here, “percent”, “%”, and the like are intended to be synonymous with “weight percent”, “vol-%”, etc.
[00029] The term ‘therapeutically effective amount’ used throughout the present disclosure denotes an amount sufficient to produce the desired effects without causing any side-effects.
[00030] The term, "subject" used throughout the present disclosure denotes an animal, preferably a mammal, and most preferably a human. The term "mammal" used herein refers to warm-blooded vertebrate animals of the class 'mammalia', including humans, characterized by a covering of hair on the skin and in the female, milk-producing mammary glands for nourishing the young. The term mammal includes animals such as cat, dog, rabbit, bear, fox, wolf, monkey, deer, mouse, pig and human.
[00031] In some embodiments, the numbers expressing quantities of ingredients, properties such as concentration, reaction conditions, and so forth, used to describe and claim certain embodiments of the invention are to be understood as being modified in some instances by the term “about”. Accordingly, in some embodiments, the numerical parameters set forth in the written description are approximations that can vary depending upon the desired properties sought to be obtained by a particular embodiment. In some embodiments, the numerical parameters should be construed in light of the number of reported significant digits and by applying ordinary rounding techniques. Notwithstanding that the numerical ranges and parameters setting forth the broad scope of some embodiments of the invention are approximations, the numerical values set forth in the specific examples are reported as precisely as practicable.
[00032] The recitation of ranges of values herein is merely intended to serve as a shorthand method of referring individually to each separate value falling within the range. Unless otherwise indicated herein, each individual value is incorporated into the specification as if it were individually recited herein.
[00033] The headings and abstract of the invention provided herein are for convenience only and do not interpret the scope or meaning of the embodiments.
[00034] The following discussion provides many example embodiments of the inventive subject matter. Although each embodiment represents a single combination of inventive elements, the inventive subject matter is considered to include all possible combinations of the disclosed elements. Thus if one embodiment comprises elements A, B, and C, and a second embodiment comprises elements B and D, then the inventive subject matter is also considered to include other remaining combinations of A, B, C, or D, even if not explicitly disclosed.
[00035] Few key targets such as dermal papilla cells, androgen receptor, 5-alpha reductase and Ornithine decarboxylase (ODC) enzyme play a very important role in hair follicle growth and development. Particularly, dermal papilla cells act as a signaling centre for initiating growth and re-generation of hair follicles and their reduction lowers the blood supply to hair follicles and promote hair fall. Similarly, Ornithine decarboxylase (ODC) enzyme is also responsible for synthesis of several small ions and polyamines required for hair follicle growth and development. Inventors of the present disclosure realized that inhibition of dermal papilla cells proliferation, androgen receptor, 5-alpha reductase and ornithine decarboxylase reduce the possibility of hair growth and development. Accordingly, based on extensive experimentation and research, inventors of the present disclosure have arrived at optimized synergistic compositions that inhibit such target cells and enzymes and effectively treat hirsutism without causing any significant side-effects. Surprisingly, the composition exhibits superior storage stability and synergistic activity /functional reciprocity.
[00036] In an embodiment, the present disclosure provides a pharmaceutical composition for management of hirsutism comprising curcumin in a range of about 0.01% w/w to about 5% w/w, Cyperus rotundus in a range of about 0.01% w/w to about 5% w/w, green tea in a range of about 2% w/w to about 45% w/w, soya protein in a range of about 30% w/w to about 60% w/w; natural oils in a range of about 0.1% w/w to about 5% w/w; Hamamelis in a range of about 0.01% w/w to about 5% w/w; and one or more pharmaceutically acceptable excipient(s) in a range of about 0.1% w/w to about 20% w/w.
[00037] In a preferred embodiment, curcumin may be present in the composition in a range of about 0.1% w/w to about 0.5% w/w.
[00038] In an embodiment, soya protein may be present in the composition in a range of about 50% w/w to about 60% w/w.
[00039] Cyperus rotundus or purple sedge is a perennial sedge plant belonging to the Cyperaceae family. It is a widespread, crop-damaging, invasive weed found worldwide including waste lands, river banks, and agricultural fields. It has been used in the past for treatment of digestive disorders and its tubers may be consumed as food.
[00040] In an embodiment, the Cyperus rotundus may be whole of Cyperus rotundus, part of Cyperus rotundus, an extract of Cyperus rotundus or combinations thereof. The part or extract of Cyperus rotundus may be selected from the group comprising of root, leaves, shoot, fruits, rhizome, seed, stem, barks, flower, sap, bud and combinations thereof of the plant. In a preferred embodiment, Cyperus rotundus may be Cyperus rotundus oil.
[00041] In a preferred embodiment, Cyperus rotundus may be present in the composition in a range of about 0.1% w/w to about 0.5% w/w.
[00042] In an embodiment, green tea may be present as green tea extract. In a preferred embodiment, green tea may be present in the composition in a range of about 30% w/w to about 40% w/w.
[00043] In an embodiment, the natural oils may be selected from fenugreek oil, almond oil, turmeric oil, sunflower oil, spearmint oil, castor oil, basil oil, coconut oil, olive oil, lavender oil, or combinations thereof.
[00044] In a preferred embodiment, the natural oils may be present in the composition in a range of about 1% w/w to about 3% w/w.
[00045] Hamamelis or Witch Hazel is a shrub native to North America belonging to the family Hamamelidaceae. It bears pale to yellow/orange flowers during the flowering season. It has been known for providing relief from itching, or swelling.
[00046] In an embodiment, the Hamamelis may be whole of Hamamelis, part of Hamamelis, an extract of Hamamelis, or combinations thereof. In a preferred embodiment, the composition comprises an extract of Hamamelis.
[00047] In a preferred embodiment, Hamamelis may be present in the composition in a range of about 0.1% w/w to about 2% w/w.
[00048] The extract or part may be obtained from root, leaves, shoot, fruits, rhizome, seed, stem, barks, flower, sap, bud and combinations thereof of the plant.
[00049] In an embodiment, the extracts employed may be naturally isolated or commercially available extract thereof can also be used for realizing the composition of the present disclosure. Extracts may be available in concentrated liquid or dried powder form. However, extract prepared by any other method for isolation and extraction of active compounds, as known to or appreciated by a person skilled in the art, for example, maceration, soxhlet extraction, microwave-assisted extraction (MAE), ultrasound-assisted extraction (UAE), or supercritical fluid extraction (SFE) can be used to serve its intended purpose, as laid down in the present disclosure without departing from the scope and spirit of the present disclosure.
[00050] In an embodiment, the pharmaceutically acceptable excipient is selected from any or a combination of a thickening agent, a stabilizing agent, a humectant, a moisturizing agent, a bulking agent, a diluent, a solubilizer, a binder, a disintegrant, a chelating agent, a glidant, a flavouring agent, a colouring agent, a sweetening agent, a tonicity agent, an anti-irritant, anti-microbial, a buffering agent, a preservative, lubricant, a co-solvent, or combinations thereof. However, a person skilled in the art would appreciate that any other excipient(s) can be utilized to serve the intended purpose without departing from the scope and spirit of the disclosure.
[00051] In a preferred embodiment, the excipients present in the composition may range of about 5% w/w to about 15% w/w.
[00052] In an embodiment, bulking agent(s) include but not limited to, lactose USP, Starch 1500, mannitol, sorbitol, maltodextrin, malitol or other non-reducing sugars; microcrystalline cellulose (e.g., Avicel), dibasic calcium phosphate (anhydrous or dihydrate), sucrose, etc. and mixtures thereof. However, a person skilled in the art would appreciate that any other bulking agent(s) can be utilized to serve the intended purpose without departing from the scope and spirit of the disclosure.
[00053] In an embodiment, solubilizer(s) includes but not limited to, cyclodextrins, pH adjusters, salts and buffers, surfactants, fatty acids, phospholipids, metals of fatty acids and the likes. However, a person skilled in the art would appreciate that any other solubilizer(s) can be utilized to serve the intended purpose without departing from the scope and spirit of the disclosure.
[00054] In an embodiment, binder(s) include but not limited to, cellulosic derivatives (such as methylcellulose, carboxymethyl cellulose, hydroxyethyl cellulose, hydroxyethylmethyl cellulose, etc), polyacrylates (such as Carbopol, polycarbophil, etc), Povidone (all grades), Polyox of any molecular weight or grade, irradiated or not, maize starch, povidone, copovidone, corn starch, starch, polyvinylpyrrolidone (PVP), microcrystalline cellulose (Avicel@ -Avicel 101), and the like. However, a person skilled in the art would appreciate that any other binder(s) can be utilized to serve the intended purpose without departing from the scope and spirit of the disclosure.
[00055] In an embodiment, glidant(s) includes but not limited to, colloidal silicon dioxide, precipitated silicon dioxide, fumed silica (CAB-O-SIL M-5P, trademark of Cabot Corporation), stearowet and sterotex, silicas (such as SILOID and SILOX silicas—trademarks of Grace Davison Products, Aerosil—trademark of Degussa Pharma), higher fatty acids, the metal salts thereof, hydrogenated vegetable oils and the like. However, a person skilled in the art would appreciate that any other glidant(s) can be utilized to serve the intended purpose without departing from the scope and spirit of the disclosure.
[00056] In an embodiment, flavoring agent(s) includes but not limited to, fruit aromas such as orange, banana, strawberry, cherry, wild cherry, lemon; cardamom, anis, mint, menthol, vanillin, and ethyl vanillin, and other similar aromas such as coffee, or the mixtures thereof. However, a person skilled in the art would appreciate that any other flavoring agent(s) can be utilized to serve the intended purpose without departing from the scope and spirit of the disclosure.
[00057] In an embodiment, sweetening agent(s) includes but not limited to, sucralose, acesulfame-K, aspartame, saccharine or saccharine sodium and calcium salts, sodium cyclamate, sucrose, fructose, glucose, sorbitol, or the mixtures thereof. However, a person skilled in the art would appreciate that any other sweetening agent(s) can be utilized to serve the intended purpose without departing from the scope and spirit of the disclosure.
[00058] In an embodiment, buffer system includes but not limited to, sodium citrate, potassium citrate, sodium citrate di-hydrate, citric acid, citric acid monohydrate, sodium bicarbonate, potassium bicarbonate, sodium di-hydrogen phosphate and potassium di-hydrogen phosphate and the likes or combination thereof. However, a person skilled in the art would appreciate that any other buffer system can be utilized to serve the intended purpose without departing from the scope and spirit of the disclosure.
[00059] In an embodiment, disintegrant(s) includes but not limited to, croscarmellose sodium, Crospovidone, sodium starch glyconate, citric acid, calcium carbonate, pregelatinized starch and mixture thereof. However, a person skilled in the art would appreciate that any other disintegrant(s) can be utilized to serve the intended purpose without departing from the scope and spirit of the disclosure.
[00060] In an embodiment, lubricant(s) includes but not limited to, zinc stearate, magnesium stearate, stearic acid, calcium stearate, Vegetable stearin and mixture thereof. However, a person skilled in the art would appreciate that any other lubricant(s) can be utilized to serve the intended purpose without departing from the scope and spirit of the disclosure.
[00061] In an embodiment, diluent(s) includes but not limited to, microfine cellulose, lactose, starch, pregelatinized starch, calcium carbonate, calcium sulfate, sugar, dextrates, dextrin, dextrose, dibasic calcium phosphate dihydrate, tribasic calcium phosphate, kaolin, magnesium carbonate, magnesium oxide, maltodextrin, mannitol, potassium chloride, powdered cellulose, sodium chloride, sorbitol, talc and mixture thereof. However, a person skilled in the art would appreciate that any other diluent(s) can be utilized to serve the intended purpose without departing from the scope and spirit of the disclosure.
[00062] In an embodiment, flavoring agent(s) includes but not limited to, fruit aromas such as orange, banana, strawberry, cherry, wild cherry, lemon; cardamom, anis, mint, menthol, vanillin, and ethyl vanillin, and other similar aromas, sodium benzoate or the mixtures thereof. However, a person skilled in the art would appreciate that any other flavoring agent(s) can be utilized to serve the intended purpose without departing from the scope and spirit of the disclosure.
[00063] In an embodiment, thickening agent(s) includes but not limited to, carbopol, carbomer, acrylate copolymer, beeswax, emulsifying CresmerWax, sodium acrylate/sodiumacryloyldimethyltaurate copolymer or the mixtures thereof. However, a person skilled in the art would appreciate that any other thickening agent(s) can be utilized to serve the intended purpose without departing from the scope and spirit of the disclosure.
[00064] In an embodiment, stabilizing agent(s) includes but not limited to, EDTA Disodium, Sodium gluconate,Tetrasodium EDTA, Sodium Phytate, citric acidor the mixtures thereof. However, a person skilled in the art would appreciate that any other stabilizing agent(s) can be utilized to serve the intended purpose without departing from the scope and spirit of the disclosure.
[00065] In an embodiment, humectant(s) includes but not limited to, Glycerine, Propylene Glycol, Butylene glycol, aloe-vera gel, hexylene glycol, glyceryl triacetate, Sodium hyaluronate or the mixtures thereof. However, a person skilled in the art would appreciate that any other humectant(s) can be utilized to serve the intended purpose without departing from the scope and spirit of the disclosure.
[00066] In an embodiment, moisturizing agent(s) includes but not limited to, ceramide, borage oil, tocopherol, tocopherol linoleate, dimethicone, Allantoin, hyaluronic acid, sodium peroxylinecarbolic acid, wheat protein, hair keratin amino acids, Gelatin, glycospingolipids, retinol, lactic acid, lanolin, sodium acrylate or sodium acryloyl dimethyl taurate copolymer or mixtures thereof. However, a person skilled in the art would appreciate that any other moisturizing agent(s) can be utilized to serve the intended purpose without departing from the scope and spirit of the disclosure.
[00067] In an embodiment, preservative(s) includes but not limited to, potassium sorbate, phenoxyethanol, DMDM, p-hydroxybenzoic acid esters, sorbic acid, benzoic acid, propionic acid or salts thereof; alcohols such as benzyl alcohol, butanol or ethanol, isopropyl alcohol and quaternary ammonium compounds such as benzalkonium chloride, sodium benzoate and mixture thereof. However, a person skilled in the art would appreciate that any other preservative(s) can be utilized to serve the intended purpose without departing from the scope and spirit of the disclosure.
[00068] In an embodiment, the anti-irritant(s) may include camphor, Allantoin, menthol, or combinations thereof. However, a person skilled in the art would appreciate that any other anti-irritant(s) can be utilized to serve the intended purpose without departing from the scope and spirit of the disclosure.
[00069] In an embodiment, the composition may comprise a solvent. In an embodiment, solvent includes but is not limited to, methanol, ethanol, n-propanol, isopropanol, hexane, heptane, petroleum ether, cyclohexane, diethyl ether, diisopropyl ether, ethyl acetate, methyl acetate, ethyl formate, methyl formate, isobutyl acetate, n-butyl acetate, methylene chloride, ethylene chloride, chloroform, carbon tetrachloride, acetone, ethyl methyl ketone, diisobutyl ketone, methyl isobutyl ketone, 1,4- dioxane, toluene, ammonia solution, glacial acetic acid, ammonium hydroxide, sodium hydroxide, calcium hydroxide, calcium carbonate, potassium hydroxide, potassium carbonate, water, or combinations thereof. However, a person skilled in the art would appreciate that any other solvent or a combination of solvents can be utilized to serve the intended purpose without departing from the scope and spirit of the disclosure.
[00070] In an embodiment, the solvent may be present in the composition in a range of about 10% w/w to about 99% w/w.
[00071] The pharmaceutical compositions detailed herein can be manufactured in one or several dosage forms. In an embodiment, pharmaceutical dosage form is selected from any or a combination of capsule, tablets or caplets; pills; powders such as a sterile packaged powder, a dispensable powder, and an effervescent powder; capsules including both soft or hard gelatin capsules such as HPMC capsules, lozenges, a sachet, a sprinkle, a reconstitutable powder or shake, a troche, granules, liquids such as suspensions, emulsions, semisolids, or gels, a paste, a cream, foam, lotions and an ointment. In an embodiment, the formulation may be in a solid, a liquid and a semi-solid form. However, any or a combination of pharmaceutical dosage form(s), as known to or appreciated by a person skilled in the art, can be utilized to serve its intended purpose, as laid in the present disclosure, without departing from the scope and spirit of the present disclosure.
[00072] In an embodiment, the pharmaceutical composition is formulated into a capsule, a tablet, a pill, a powder, a sachet, a cream, a spray, nanoparticles cream, nanoparticles gel, gel, foam, a lotion, an ointment or a paste. In another embodiment, the formulation may be suitable for topical application. Preferably, the formulation is in the form of a paste, a cream, a gel, foam, a lotion and an ointment for topical application on the affected areas.
[00073] In a preferred embodiment, the formulation is a cream.
[00074] In an embodiment, the present disclosure provides a pharmaceutical cream formulation for management of hirsutism comprising curcumin in a range of about 0.01% w/w to about 5% w/w, Cyperus rotundus in a range of about 0.01% w/w to about 5% w/w, green tea in a range of about 2% w/w to about 45% w/w, soya protein in a range of about 30% w/w to about 60% w/w; natural oils in a range of about 0.1% w/w to about 5% w/w; Hamamelis in a range of about 0.01% w/w to about 5% w/w; and one or more pharmaceutically acceptable excipient(s) in a range of about 0.1% w/w to about 20% w/w.
[00075] In an embodiment, the formulation comprises a curcumin in about 0.1% w/w to about 0.5% w/w, extract of Cyperus rotundus in about 0.1% w/w to about 0.5% w/w, extract of green tea in about 30% w/w to about 40% w/w, soya protein in about 50% w/w to about 60% w/w, natural oils in about 1% w/w to about 3% w/w, extract of Hamamelis in about 0.1% w/w to about 2% w/w and one or more pharmaceutically acceptable excipient(s) in about 5% w/w to about 15% w/w.
[00076] In an embodiment, the present disclosure provides a pharmaceutical cream formulation for management of hirsutism comprising curcumin, extract of Cyperus rotundus, extract of green tea, soya protein, fenugreek oil, almond oil, turmeric oil, sunflower oil, spearmint oil, castor oil, basil oil, extract of Hamamelis, allantoin, menthol, camphor, sodium acrylate/sodium acryloyl dimethyl taurate copolymer, DMDM hydantoin, and water.
[00077] The composition shows inhibition of dermal papilla cells proliferation, inhibition of androgen receptor, inhibition of 5-alpha reductase, and inhibition of ornithine decarboxylase.
[00078] The composition targets key cellular pathways to modulate hirsutism and exhibits decrease in proliferation, growth rate and mitotic activity of dermal papilla cells. It also shows delay in attainment of black skin, delay in anagen induction, slow hair growth rate, reduced hair density and visual melanogenesis. The composition further exhibits decrease in follicles in subcutis, reduction in total number of follicles and reduced skin thickness.
[00079] In an embodiment, the composition synergistically improves the condition of hirsutism compared to individual components. The composition shows inhibition of hair growth. It has efficacy comparative with Eflornithine.
[00080] In an embodiment, the present disclosure relates to a process of preparing a composition or formulation for management of hirsutism.
[00081] In an embodiment, the present disclosure provides a process of preparing a pharmaceutical composition comprising the steps of: (a) taking flocare and dissolving it in water for base; (b) dissolving basil oil, menthol, and DMDM hydantoin in the base with continuous stirring; (c) taking soya protein, curcumin, green tea, sodium acrylate/sodium acryloyl dimethyl taurate copolymer and Cyprus rotundus in a separate container and dissolving them in water; (d) mixing the solution of step (c) and step (b); (e) preparing organic phase by taking castor oil, spearmint oil, sunflower oil, almond oil, camphor, turmeric oil, fenugreek oil, Hamamelis extract and allantoin and heating at about 50-70 ºC till clear solution is obtained; and (f) mixing the solution of step (d) and the organic phase of step (e) to give the formulation.
[00082] In an embodiment, the present disclosure provides a method of treatment, amelioration or prophylaxis of hirsutism in a subject by administering a therapeutically effective amount of the pharmaceutical composition as recited above.
[00083] The therapeutically effective amount of the composition may be determined by a trained physician based on the subject’s age, gender, medical fitness, severity of the condition, past medical records, hormonal variation, among other well-established factors well-known to a physician.
[00084] In a preferred embodiment, the composition is a pharmaceutical cream formulation which is topically applied and spread, smeared or rubbed onto the affected area. The composition is easy to apply, safe, non-allergic, non-comedogenic, moisturizing, penetrates into skin quickly, and gives faster and sustained results.
[00085] In an embodiment, the composition may be applied once, twice or multiple times depending on the severity of condition.
[00086] In an embodiment, the present disclosure relates to use of a pharmaceutical composition as recited above for treatment, prevention or amelioration of hirsutism. In an embodiment, the present disclosure relates to use of a pharmaceutical composition as recited above in a medicament for management of hirsutism.
[00087] Although the subject matter has been described in considerable detail with reference to certain preferred embodiments thereof, other embodiments are possible. While the foregoing describes various embodiments of the disclosure, other and further embodiments of the disclosure may be devised without departing from the basic scope thereof. The scope of the invention is determined by the claims that follow. The invention is not limited to the described embodiments, versions or examples, which are included to enable a person having ordinary skill in the art to make and use the invention when combined with information and knowledge available to the person having ordinary skill in the art.
EXAMPLES
[00088] 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.
[00089] MATERIALS: The extracts employed in the formulation were commercially obtained from sources as mentioned in Table 1.

Table 1: Source of extracts
S. No. INGREDIENTS MANUFACTURERS
1. Basil Oil Northern Aromatics Limited, UP, India
2. Menthol Hindustan Mint &Agro Products, UP, India
3. Soya protein Herbo nutra, UP, India
4. Curcumin Herbo nutra, UP, India
5. Extract of Cyprus rotundus Herbo nutra, UP, India
6. Extract of Green tea Herbo nutra, UP, India
7. Castor Oil Shiv Sales Corp, UP, India
8. Spearmint Oil Shiv Sales Corp, UP, India
9. Sunflower Oil Shiv Sales Corp, UP, India
10. Almond Oil Shiv Sales Corp, UP, India
11. Camphor Shiv Sales Corp, UP, India
12. Turmeric Oil Shiv Sales Corp, UP, India
13. Fenugreek Oil Shiv Sales Corp, UP, India
14. Hamamelis (Witch Hazel) Extract Herbo nutra, UP, India

Example 1
Preparation of a cream formulation
[00090] A cream formulation having composition as per Table 2 was prepared. To prepare a water phase solution, some amount of water was taken and flocare (cream base) was dissolved in it to form a clear gel solution. DMDM, menthol and basil oil were added to it with continuous stirring. In another beaker, remaining amount of water was taken and soya protein, curcumin, extract of green tea, sodium acrylate/sodium acryloyl dimethyl taurate copolymer and extract of Cyprus rotendus were dissolved in it to form a solution. This solution was added in the previously prepared solution. To prepare an organic phase solution castor oil, spearmint oil, sunflower oil, almond oil, camphor, turmeric oil, fenugreek oil, witch hazel extract and allantoin were taken and heated at about 70 ºC to obtain a clear solution. The organic phase was added to the water phase with continuous mixing to form the cream formulation.
Table 2: Composition of cream formulation
S. No. Ingredients Amount (%w/w)
1. Soya protein 49.61
2. Curcumin 0.35
3. Cyprus rotundus 0.35
4. Green tea 35.43
5. Natural oils:
Basil oil, Castor oil, Spearmint oil, Sunflower oil, Almond oil, Turmeric oil, Fenugreek oil 2.49
6. Witch Hazel Extract 0.70
7. Excipient:
Camphor, Menthol, Allantoin, Sodium Acrylate/Sodium Acryloyl Dimethyl Taurate Copolymer, DMDM 11.12

[00091] For preparing the above formulation individual components were used in amounts as disclosed in Table 3 below. Water was taken in quantity sufficient.
Table 3: Specific composition
S. No. Ingredients/Herbs mg
1. Sodium Acrylate/Sodium Acryloyl Dimethyl Taurate Copolymer 1.00
2. Basil Oil 0.01
3. Menthol 0.01
4. DMDM 0.05
5. Soya protein 7.00
6. Curcumin 0.05
7. Cyprus rotendus 0.05
8. Green tea 5.00
9. Castor oil 0.10
10. Spearmint oil 0.01
11. Sunflower oil 0.10
12. Almond oil 0.10
13. Camphor 0.01
14. Turmeric oil 0.01
15. Fenugreek Oil 0.01
16. Witch hazel extract 0.10
17. Allantoin 0.50
Total 14.11

[00092] Surprisingly, the formulation of the present disclosure exhibited superior storage stability and functional reciprocity/strong synergy there between, and hence, the formulation of the present disclosure holds the potential for widespread usage in treatment, prevention and amelioration of hirsutism.
[00093] The foregoing examples are merely illustrative and are not to be taken as limitations upon the scope of the invention. Various changes and modifications to the disclosed embodiments will be apparent to those skilled in the art. Such changes and modifications may be made without departing from the scope of the invention.

ADVANTAGES OF THE INVENTION
[00094] The present disclosure provides a composition that does not possess any side-effects over prolonged usage.
[00095] The present disclosure provides a composition that exhibits superior storage stability and synergistic activity /functional reciprocity.
[00096] The present disclosure provides a composition with in vitro efficacy in decreasing proliferation, growth rate and mitotic activity of HFPDCs.

[00097] The present disclosure provides a composition that shows delay in attainment of black skin, delay in anagen induction, slow hair growth rate, reduced hair density and visual melanogenesis.
[00098] The present disclosure provides acomposition that is easy to prepare and economical.

WE CLAIMS:

1. A pharmaceutical composition for management of hirsutism comprising curcumin in a range of 0.01% w/w to 5% w/w, Cyperus rotundus in a range of 0.01% w/w to 5% w/w, green tea in a range of 2% w/w to 45% w/w, soya protein in a range of 30% w/w to 60% w/w; natural oils in a range of 0.1% w/w to 5% w/w; Hamamelis in a range of 0.01% w/w to 5% w/w; and one or more pharmaceutically acceptable excipient(s) in a range of 0.1% w/w to 20% w/w
2. The composition as claimed in claim 1, wherein curcumin is present in a range of 0.1% w/w to 0.5% w/w.
3. The composition as claimed in claim 1, wherein soya protein is present in the range of 50% w/w to 60% w/w.
4. The composition as claimed in claim 1, wherein Cyperus rotundus is present in the range of 0.1% w/w to 0.5% w/w.
5. The composition as claimed in claim 1, wherein green tea is present in the range of 30% w/w to 40% w/w.
6. The composition as claimed in claim 1, wherein the natural oils are selected from fenugreek oil, almond oil, turmeric oil, sunflower oil, spearmint oil, castor oil, basil oil, or combinations thereof and are present in the range of 1%w/w to 3%w/w.
7. The composition as claimed in claim 1, wherein Hamamelis is present in a range of 0.1% w/w to 2% w/w.
8. The composition as claimed in claim 1, wherein the pharmaceutically acceptable excipient is selected from any or a combination of a thickening agent, a stabilizing agent, a humectant, a moisturizing agent, a bulking agent, a diluent, a solubilizer, a binder, a disintegrant, a chelating agent, a glidant, a flavouring agent, a colouring agent, a sweetening agent, a tonicity agent, an anti-irritant, anti-microbial, a buffering agent, a preservative, lubricant, a co-solvent, or combinations thereof.
9. The composition as claimed in claim 1, wherein the composition is formulated into a capsule, a tablet, a pill, a powder, a sachet, a cream, a spray, nanoparticles cream, nanoparticles gel, gel, foam, a lotion, an ointment or a paste.
10. A pharmaceutical cream formulation for management of hirsutism comprising curcumin in a range of 0.01% w/w to 5% w/w, Cyperus rotundus in a range of 0.01% w/w to 5% w/w, green tea in a range of 2% w/w to 45% w/w, soya protein in a range of 30% w/w to 60%w/w; natural oils in a range of 0.1% w/w to 5% w/w; Hamamelis in a range of 0.01% w/w to 5% w/w; and one or more pharmaceutically acceptable excipient(s) in a range of 0.1% w/w to 20% w/w.