FIELD OF THE INVENTION
The present invention relates to a cosmetic / dermopharmaceutical composition comprising a hair growth promoting/ stimulating/ enhancing or preventing hair loss agent comprising an effective amount of phenolic active compounds or its derivatives and cosmetically/ dermopharmceutically accepted vehicle with or without other skin/hair care benefit agents. Specifically, the invention relates to a dermopharmaceutical composition for external application in promoting or enhancing or stimulating hair growth or preventing hair loss. The invention particularly relates to phenolic compound as the active ingredient of Formula 1 represented hereunder

Wherein
R1 represents H or alkyl or C (O)-alkyl
R2 represents C1-C6 Linear/ branched alkyl
R3 represents H, C1-C6 Linear/ branched alkyl
More specifically, the present invention provides simple and cost effective hair care benefiting agents comprising phenolic active compounds selected from one or more of Thymol and Carvacrol, of Formula 1 preferably sourced from safe and renewable sources such as plants, which can be used singly or in combination with cosmetically/ dermopharmaceutically acceptable vehicle/ carriers.
BACKGROUND OF THE INVENTION
Various studies to treat hair loss and promote hair growth in men and women who suffer serious mental anguish in being not too beautiful due to genetic or environmental hair loss problems are being actively conducted world wide. Hair disorder, especially when severe, often profoundly affects the lives of those afflicted. Hair growth and better hair coverage are the long felt needs of every human being
- 2 -

who suffer from hair fall/ loss problem. The other unmet requirements are reduction in hair fall and thinning. Decreased growth of hair in terms of length is also another common problem seeking attention.
Human hairs are about 1, 00, 000 - 1, 50, 000 in number, and each individual hair grows and falls out through various cycles of hair growth. Hair undergoes three phases of growth: anagen, catagen and telogen. The anagen is a hair growth phase, followed by the catagen phase when the configuration of hair Is maintained and at the same time the metabolic process thereof becomes slow. The telogen following the catagen is a phase when hair papilla becomes smaller and hair follicles become recessive, so that hair shafts are easily shed out. This life cycle of hair can vary depending on various conditions, including nutritional status, medical history, heredity, physical constitution, hormone secretion and aging.
The hair fall or decrease in hair density could be due to several reasons. Aging, scalp infections, production of excessive sebum, post effect of certain diseases such as typhoid, jaundice, malaria, cardiovascular, smoking, hormonal imbalance, conversion of testosterone to 5-alpha dihydrotestosterone, reduction in anagen hair either due to anagen or telogen effluvium are the major contributing factors for hair fall/ loss problems, Poor nutrition and other general physiological reasons are also known to add to hair fall/ loss problems. Autoimmune disorders do play a role as in the case of alopecia.
Several attempts have been made to develop medicaments to address the above discussed problem. All the available preparations/ medicaments either increase anagen hair or augment neogenesis of hair follicle or reverse the effluvium status. Vasodilatation of the micro capillaries resulting in increased nutrient availability to the hair follicle is also one of the mechanisms by which the problem is addressed. Although Minoxidil is known to be effective, but augment predominantly fine hair formation. On withdrawal of the medicament, hair fall problem recurs, The hormone-based treatment is also known to have several side effects. Serious safety concern, poor efficacy, individual variability and continuous dependence to the therapy limit the available line of treatment for the above problem.
Also, an oral administration drug, Finasteride which inhibits the action of 5-alpha-reductase to hinder the production of dihydrotestosterone, a potent male hormone was approved by the US FDA and is being marketed as a hair growth stimulant.

However, its use has been limited in being expensive with various side effects (Park, W. S. et al., WO 2007/046577 Al, 2007).
The other important approach available for such a problem is hair transplantation through surgical method. The natural (autologus in the case of natural) or synthetic hair fibers are equidistantly weaved into the scalp. This treatment is not only expensive but also requires continuous maintenance therapy. Further, this method also does not promote hair growth or cause reduction in hair fail.
Therefore, there remains a need in the art for an effective and safe hair growth promoter. Furthermore, since different types of alopecia are caused by different physiological mechanisms, there is a need for safe hair growth promoters or stimulators, which may be used in conjunction with other medications for alopecia in order to significantly enhance the effects of such treatments on hair growth.
US patent 5, 081, 151 discloses a method for inducing, maintaining or increasing hair growth comprising hexosaccharic acids and esters (alkyl and hydroxyalkyl esters) selected form the group consisting of allosaccharic acid, altrosaccharic acid, glucosaccharic acid, mannosaccharic acids, gulosaccharic acid, galactosaccharic acid and talosaccharic acid in addition to mioxidil. This prior art is based on the already proven and established link between intact glycosaminoglycans and hair growth where the identification of the above said molecules as the inhibitor of exoglycosidases (enzyme that breaks down glycosaminoglycans) is believed to prevent the breakdown of glycosaminoglycan chains, thereby stimulating hair growth.
US patent 6, 030, 948 illustrates a hair regeneration composition comprising a thymic extract, thymosin, prepared from calf thymus glands, a steroid, antifungal agent, a mitocide in the form of a surfactant and a fragrance such as menthol, thymol etc. This prior art is based on the fact that alopecia in humans and other warm blooded mammals is a decrease in cell mediated immunity which in turn is regulated by the thymus glands whereby the thymosin fraction 5 (TF5) has been found to be effective in reconstituting immune functions in thymic deprived or immuno deprived animals, in humans with primary immuno deficiencies. It was also surprisingly found by way of this prior art that using fragrance based chemicals like thymol (4.5-5 wt. %) as one of the chemicals, a skin penetrant (PX 13) and a surfactant gave way to an effective mitocide where it was discovered that the

ectoparasite playing a significant role in alopecia (hair loss) could effectively be eliminated.
US patent 5, 185, 325 discloses a suitable composition for topical application to mammalian skin for hair inducing, maintaining or increasing hair growth comprising of a glycosaminogiycanase inhibitor for preserving intact glycosaminoglycans necessary to promote hair growth and chosen from aldomonolactones, alduronomonolactones and acylated monosaccharides, and a cosmetically acceptable vehicle for the inhibitor. The effective amount of the glycosaminogiycanase inhibitor present in the composition is sufficient to increase hair growth in the rat by at least 20% where the said inhibitor is present in the composition varies from 0.0001 to 99 % by weight.
WO2007/046577A1 relates to hair growth promoting composition for external application comprising 4-pyrrolidine 2, 6-diaminopyrimidine 1-oxide as the active and one or more selected from the group consisting additionally Thujae semen, showing 5-alpha reductase inhibitory activity to inihibit the production of dihydrotestosterone as a potent male hormone; vitamin EJ5 derivatives like D-panthenol that has the ability to convert into pantothenic acid in the skin and hair to produce the effects of vitamin B5 etc. The composition containing the active in an amount of 0.001-10 wt. % helps in smooth supply of nutrients necessary for hair growth through the vasodilation of blood vessels around hair follicles resulting from a potassium channel opening effect to promote the transition from the telogen phase to the anagen phase of the hair cycle and to maintain the anagen phase for a longer period of time.
M. Nomura in U. S. Patent 5, 750, 107 has revealed that nicotinamide, salicylic acid also possesses hair growth properties.
F. Bonte et. al., in U. S. Patent, 5, 607, 693 have shown that some nitrogen containing molecules, like minoxidil and cantharidin are commonly used ingredients in formulations for promoting or stimulating hair growth, but some of these molecules are already showing side effects.
There are numerous extracts from several parts of plant body that have been reported to show hair growth properties such as grape seed, green tea, rosemary oil, Salvia officinalis, Aloe vera, Ginko biloba, Serenova repens, Urtica dioica. Glyceride

pentadecanoate, cepharanthin, Swertia extract liquid, soluble cysteine, ginseng extract liquid, glycyrrhetinic acid, tocopherol aceate, hinokitol, capsicum tincture, sweet grass extract etc.
WO2006/082481A1 is directed to an anti-dermatophytic composition effective for treating tinea infections, including Tinea capitis, a fungal infection of the scalp that causes hair loss, by utilizing an extract obtained from the plant Hedychium Spicatum containing ethyl p-methoxycinnamate as an active ingredient present in an amount of 4-10 wt. % optionally in combination with other bioactive substances.
US patent 6203782 is directed to methods and compositions to promote hair growth, obtained from a class of herbs selected from fennel seeds, caraway seeds and mixtures thereof sourcing anole, dianole, anethole, estragole and Fenchone etc.; which can also be obtained synthetically. The above prior art brings to light that a structure-activity relationship is imperceptible to predict the behavioral aspects of the compounds contained therein in promoting hair growth.
JP 09-157136 is directed to provide a hair restorer/ hair tonic having hair growth promoting effect comprising tocotrienol of vitamin E family (0.01-10 wt. %), forskolin or a derivative obtained from Coleus forskohlii root extract (0.00001-10 wt. %), and at least one component selected from among fatty acids, alcohols, and derivatives (0.01-20 wt. %).
Japanese patent JP 1038012, Japanese patent JP 5155738; Kobayashi, et al., Yakugaku Zasshi, 1993, 113, pp.718-724, illustrate the use of extracts from plant species Orchidaceae, Bletilla striata, Meliaceae and Lamiaceae as hair growth promoters.
US patent 6, 824, 795 is directed to the treatment of drug resistant bacterial infections e.g. systemic and enteric by the oil distilled from the seeds of plant Trachyspermum ammi (Ajwain) containing Thymol as the active ingredient in the levels of 20 to 50 % w/w. Moreover, such a treatment requires the combination of Thymol with mint oil containing an effective amount of monoterpenes. Other prior arts cited therein are related to herbal compositions containing thymol as an active for the treatment of skin infections, viral infections, analgesic composition for treating arthritis and powder composition for mouthwash.

Furthermore, several biological properties of thymol is on record; such as antifilarial activity of thymol derived from Trachyspermum ammi (M. Nisha, et. al., Molecules, 2008, 13, 2156-2168), antimicrobial activity derived from Lippia sidoides (M. A. Botelho, et. al., Brazilian Journal of Medical and Biological Research, 2007 40, 349-356J, anthelmintic activity of T. ammi seeds (3. Abdul, et. al., Pharmacognosy Magazine, 2006, 2, 126-129).
In connection to thymol, it is noteworthy to mention that the Japanese patent, JP 2003-212740, achieved a safe hair growth inhibitor for inhibiting growth or elongation of hair and provided a preparation for external use, such as a pharmaceutical, quasi-drug product, and cosmetic, containing one or more of methyl isopropyl phenols, such as thymol (5-methyl-2-isopropylphenol) and carvacrol (2-methyl-5-isopropylphenol) as active ingredients in an amount of 0.00001 to 5 wt. %. Usually, various kinds of other ingredients are blended suitably as needed for skin external preparations, such as cosmetics and drugs, for example, oil, a wetting agent, an ultraviolet ray absorbent, an antioxidant, a surface-active agent, an antiseptic, a moisturizer, perfume, water, alcohol, a thickener, etc. Evaluation test conducted using immortal homosapiens outer-root-sheath cell and followed by C3H mouse hair-growing test showed outstanding hair growth suppressing effect even in very low concentrations.
It is clearly apparent from the above existing state of the art and subsequent discussions that although several efficacious hair growth promoters are reported, there has been a continuing need in the art to provide for alternatives /superior hair care agent which would be simple, cost-effective and safe in having less or no side effects with the desired hair growth promoting effect.
OBJECTS OF THE INVENTION
It is therefore a primary object of the invention to provide for hair growth promoting agent that would be safe and compatible as hair care active agent.
Another object of the present invention is directed to a hair growth promoting formulation including a dermopharmaceutical or a cosmetic composition, containing the said hair care agent in an effective amount in association with an acceptable vehicle with or without other hair benefiting agent in the acceptable vehicle.

Yet another object of the present invention is directed to a hair growth agent and/or formulations thereof which can be sourced simply and cost-effectively for variety of hair care applications/ formulations and the like.
A further object of the present invention is especially directed to the identification of hair care benefiting agents from plant sources and to the processes of extraction of selective hair care actives from plant sources to favour hair growth promoting effect.
Still another object of the present invention is to provide hair growth promoting composition comprising of selective plant extract actives / derivatives thereof as one of the hair growth promoting agent/ s.
A still further object of the present invention is to provide hair care formulations comprising hair growth compositions from safe plant sources extracts bearing actives possessing good skin compatibility and functioning as effective hair growth agents.
SUMMARY OF THE INVENTION
Thus according to the basic aspect of the invention there is provided a cosmetic/ dermopharmceutical composition comprising a hair growth promoting/ enhancing/ stimulating or preventing hair loss agent comprising of an effective amount of phenolic active compounds or its derivatives of Formula 1.

R1 represents H or alkyl or C (O)-alkyl R2 represents Ci-C6 Linear/ branched alkyl R3 represents H, Ci-C6 Linear/ branched alkyl
In another aspect of the invention there is provided a cosmetic composition comprising a hair growth promoting agent comprising of the said phenolic active

compound of Formula 1 and is selected from one or more of phenolic compounds such as Thymol and Carvacrol of Formula 2.

It is important to clarify herein that as already discussed herein before under the background art there has been a continuing need in the art for a superior hair growth promoting agent which is simple in effecting hair growth under low effective concentrations, cheap and safe in having less or no side effects in association to the desired hair growth promoting effect. In this regard, several options were tried from natural sources by the method of screening several plant extracts for hair growth properties.
In this respect, extract of plant Trachyspermum ammi Linn, containing thymol in an amount of upto 50 % w/w was also screened to look into hair growth promoting activity.
Interestingly, the JP patent 2003-212740 referred under the background art revealed a composition containing one or more of methyl isopropyl phenols, such as thymol (5-methyl-2-isopropylphenol), carvacrol (2- methyl-5-isopropylphenol) and biosol (3-methyl-4-isopropylpheno() as active ingredients in an amount of 0.00001 to 5 wt. % where the specific phenol derivative of the type methyl isopropyl phenols showed hair growth suppression effect by acting on hair mother cells.
Most significantly, the teachings flowing from the above said Japanese patent is indicative of inhibition and suppression of hair growth by the class of compounds, comprising methyl isopropyl phenols e.g. thymol, carvacrol and biosol.

In the backdrop of the above teachings flowing from the said Japanese prior art, it is thus a surprising and selective finding of the present invention that the series of above said compounds of Formula 1 and Formula 2 comprising one or more of thymol and carvacrol as the active ingredients aid in promoting hair growth when present in effective concentrations in association with a cosmetically acceptable vehicle with or without other skin/ hair care benefiting agents.
According to the preferred aspect of the invention a cosmetic composition is provided wherein the said actives of Formula 1 is preferably selected from Thymol and Carvacrol of Formula 2 and are preferably derived from plant extracts.
Preferably, a cosmetic composition is provided wherein the active comprising of the said phenolic compound of Formula 1 is preferably selected from thymol and carvacrol are isolated from appropriate plants. Ex. Trachyspermum ammf Linn., Origanum vulgare Linn., and Thymus vulgare for thymol and Origanum vulgare Linn. for carvacrol.
In another aspect of the invention a dermopharmaceutical/ cosmetic composition for topical use is provided comprising an effective amount of hair growth promoting agent
and
a cosmetically/dermopharmaceutically acceptable vehicle with or without other skin/ hair care benefiting agents.
In yet another aspect of the invention a dermopharmaceutical/ cosmetic composition for topical use is provided comprising an effective amount of hair growth promoting actives from extracts / concentrates from appropriate plants including fruits/ seeds preferably a methanol extract / concentrate or more preferably a hexane extract / concentrate
and
a cosmetically/ dermopharmaceutically acceptable vehicle with or without other skin/ hair care benefiting agents.

In accordance with a preferred aspect of the invention a dermopharmaceutical/ cosmetic composition for topical use is provided comprising
a) 0.0001 wt. % to 20 wt. %, preferably 0.001 wt. % to 10 wt. % and more preferably 0.01 wt. % to 5 wt. % of the said hair growth promoting agent
and
b} a cosmetically/ dermopharmaceuticaJly acceptable vehicle with or without other skin/ hair care benefiting agents.
In yet another aspect of the invention a dermopharmaceutical/ cosmetic composition rs provided comprising a cosmetic composition for topical use in the form of products. Ex. creams, ointments, emulsions, gels, lotions, oils, sticks, sprays, packs, wraps, woven or non-woven wipes, films or patches as a vehicle of the said hair growth composition.
In accordance with yet another aspect of the invention a dermopharmaceutical / cosmetic composition is provided wherein the said hair growth promoting/ stimulating / enhancing or hair loss preventing agent comprises selectively any one or more of (a) pure compound of Formula 1 preferably selected from thymol and carvacrol of Formula 2; (b) an extract/ concentrate of an appropriate natural source material comprising the said compounds of Formula 1 preferably thymol and carvacrol of Formula 2; and (c ) any natural source material comprising anyone or more of the said active compounds thymol and carvacrol of Formula 2.
DETAILED DESCRIPTION OF THE INVENTION
As discussed herein before, the present invention provides a single compound or mixture of compounds as extracts or pure compounds acting as hair care and, in particular, hair growth promoting / enhancing / stimulating agent or preventing hair loss agent in a cosmetic / dermopharmaceutical composition for topical use. The invention is further related to a process for producing the said selective combination of hair care/ growth promoting actives or pure compounds / agents with or without other carriers/ hair care additives involving its selective isolation from plants (Ex.

Trachyspermum ammi Linn.} and also to processes for producing the said compositions and using it to achieve hair growth promoting or enhancing or stimulating effect.
Accordingly the present invention provides hair growth promoting / stimulating / enhancing or preventing hair loss agent comprising compounds of general Formula 1

Wherein
R1 represents H or alkyl or C (0) alkyl R2 represents Ci-C6 linear/ branched alkyl R3 represents H, CL-C6 linear/ branched alkyl
In accordance with an exemplary and non-limiting embodiment, the said phenolic active compounds or its derivatives of Formula 1 of the present invention is selected from one or more of phenolic compounds such as Thymol and Carvacrol of Formula 2 as given below.

A further aspect of the invention is based upon the selective and surprising finding that actives selected from one or more of thymol and carvacrol of Formula 2 derived from the plants can provide for cosmetic composition possessing hair growth characteristics that showed excellent hair growth promoting j enhancing/ stimulating or preventing hair loss activity.
Accordingly, in yet a further aspect of the invention there is provided a cosmetic composition for topical use wherein the said hair growth promoting / enhancing / stimulating composition comprises selectively pure compound of Formula 1 as a concentrate of an appropriate natural isolate or an extract/ concentrate of the natural source material or even the natural source material itself.
According to a further aspect of the invention, the said cosmetic composition for topical use includes hair growth promoting/ enhancing / stimulating actives comprising extracts / concentrate from plants (Ex. Fruits/ seeds of Trachyspermum ammi Linn.), The extract or concentrate is preferably in methanol or more preferably in hexane containing thymol and carvacrol from Formula 1 or specifically of Formula 2 or atleast one compound of Formula 2.
The preferable solvents are less polar solvents like: hexane, benzene, toluene etc. and chlorinated solvents like: dichloromethane, chloroform, carbon tetrachloride etc. Also, solvents such as esters like: methyl acetate, ethyl acetate; ethers like: diethyl ether, methyl ethyl ether etc.; ketones like: acetone, ethyl methyl ketone etc.; and alcohols like: methanol, ethanol, propanol, butanol etc.; and aqueous alcoholic solutions like: aq. methanol, aq. ethanol etc. and or combination thereof can be used.
In accordance with another aspect of the present invention there is provided a process for the extraction and isolation of hair care agent comprising of at least one active compound of Formula 2 preferably from a plant source (Ex. Trachyspermum ammi Linn.)


comprising the steps of:
a) Subjecting a selective source from plants, in powder form, to solvent extraction technique to provide an extract,
b) Removing the solvent from the extract under vacuum to provide a concentrate
c) Subjecting the concentrate to column chromatography,
d) Pooling the active fractions and concentrating the resulting solution to
dryness in vacuo to provide for a concentrate and obtaining there from atleast
one active agent of the above said Formula 2.
Accordingly, the invention provides: for a selective compound as hair growth promoting/ enhancing /stimulating agent in a cosmetic and/ or dermopharmaceutical composition for topical use, for a process for producing the said composition either by isolation from natural sources, as a single entity or in a semi pure mixture of compounds of Formula 2 to achieve hair growth promoting/ enhancing / stimulating or preventing hair loss effect.
It is thus possible by way of the present invention to provide for a selective hair growth promoting or stimulating/ enhancing agents sourced from plant (Ex. T. ammi Linn.) that would be safe and compatible as a hair care active agent.
In another aspect, the present invention relates to a process for providing a compound isolated from plants to be used as active ingredient in the cosmetic compositions of the invention. The processes may be devised through isolation

procedures from renewable natural resources such as plants. The process for isolating the compound from Trachyspermum ammi Linn., of the invention comprises their extraction from fruits/seeds, in air-dried form, using appropriate solvents, followed by purifying the extract and separating the compound/s of the invention according to procedures generally known to those skilled in the art. The isolation process may result in a pure compound of the invention or in a mixture of the compounds of the invention in different and defined proportions, or in an extract enriched in the compound/s of the invention.
Importantly, the inventive compounds and compositions are directed to meet the much required simple, cost-effective and variety of hair care applications/ formulations and the like which would be safe for topical use.
In accordance with another aspect of invention a dermopharmaceutical/ cosmetic composition for topical use is provided comprising an effective amount of hair growth promoting / stimulating / enhancing agent and a cosmetically acceptable vehicle with or without other skin/ hair care benefiting agents.
In accordance with a further aspect of the invention, a dermopharmaceutical/ cosmetic composition for topical use comprises of
a) 0.0001 wt. % to 20 wt. %, preferably 0.001 wt. % to 10 wt. % and more
preferably 0.01 wt. % to 5 wt. % of the said hair growth promoting / stimulating /
enhancing agent
and
b) a cosmetically/ dermopharmaceutlcally acceptable vehicle with or without other
skin/ hair care benefiting agents.
Specifically various components are included in the cosmetic hair care compositions of the present invention that are usually used for cosmetic compositions such as, an aqueous component, an oily component, a powder component, alcohols, esters, a surfactant, a moisturizer, a whitening agent, an antioxidant, an ultraviolet ray absorbent, a thickener, a coloring material, perfume, an anti-oxidant, pH regulator, a chelating agent, and antiseptics, that can be blended with these cosmetics.

The ingredients essentially employed in such a composition of this invention are surfactants, oil bodying agents, emulsifiers, fats and waxes, stabilizers, polymers, silicone compounds, deodorants and antimicrobial agents, film formers, swelling agents preservatives, thickeners / herbal extracts / concentrates / active ingredients, pH adjusting agents, perfumes oils, and water to qs.
The composition according to the invention can be used for the production of cosmetic and/or dermopharmaceuticai preparations for topical use in the form of products, e.g. lotions, creams, gels, oils, sticks, sprays, packs, wraps, woven or non-woven wipes, films, patches, alcoholic and aqueous/ alcoholic solutions, emulsions, wax/fat compositions, as a vehicle of the said hair growth composition.
These preparations can also comprise further auxiliaries and additives, such as, surfactants, oily bodies, emulsifiers, pearlescent waxes, bodying agents, thickeners, superfatting agents, stabilizers, polymers, silicone compounds, fats, waxes, lecithins, phospholipids, biogenic active ingredients, deodorants, antiperspirants, film formers, swelling agents, hydrotropes, solubilizers, preservatives, perfume oils, dyes, pH regulating agents and the like.
Thus the hair care composition of the invention can also incorporate conventional cosmetic and hair/ skin care ingredients as discussed hereunder:
Surfactants
Surface-active substances which may be present are anionic, nonionic, cationic and/or amphoteric surfactants, the content of which in the compositions is usually about 1 to 70% by weight, preferably 5 to 50% by weight and in particular 10 to 30% by weight.
Oily Bodies
Suitable oily bodies can also be incorporated which include for example, Guerbet alcohols based on fatty alcohols having 6 to 18, preferably 8 to 10, carbon atoms, esters of linear C6 -C22-fatty acids with linear or branched C6-C22-fatty alcohols or esters of branched C6-C13-carboxylic acids with linear or branched C6-C22-fatty alcohols. Such oily bodies can be used in amounts of 0.1 to 50.0 % by wt.

Emulsifiers
Suitable emulsifiers are, for example, nonionic surfactants.
The addition products of ethylene oxide and/ or of propylene oxide onto fatty alcohols, fatty acids, alkylphenols or onto castor oil are also known, commercially available products which can be included. Alkyl and/or alkenyl oligoglycosides, their preparation and their use are known from the prior art.
Furthermore, zwitterionic surfactants can be used as emulsifiers. The term "zwitterionic surfactants" refers to those surface-active compounds which carry at least one quaternary ammonium group and at least one carboxylate and one sulfonate group in the molecule. Likewise suitable emulsifiers are ampholytic surfactants. The term "ampholytic surfactants" means those surface-active compounds which, apart from a C.sub.8/18- alkyl or -acyl group in the molecule, contain at least one free amino group and at least one — COOH or —S03H group and are capable of forming internal salts. Finally, cationic surfactants are also suitable emulsifiers, those of the quaternary ester type, preferably methyl quaternized difatty acid triethanolamine ester salts, being particularly preferred. Such emulsifiers can be used in amounts of 0.1 to 50.0 % by wt.
Pats, hydrocarbons and Waxes
Typical examples of fats are glycerides, i.e. solid or liquid vegetable or animal products which consist essentially of mixed glycerol esters of higher fatty acids, hydrocarbons are obtained from petroleum products, which contains more than 20 carbon atoms, suitable waxes are inter alia natural waxes. In addition to the fats, suitable additives are also fat-like substances, such as lecithins and phospholipids. The term lecithin is understood by the person skilled in the art as meaning those glycerophospholipids which form from fatty acids, glycerol, phosphoric acid and choline by esterification. Lecithins are thus frequently also known as phosphatidylcholines (PC). Examples of natural lecithins which may be mentioned are the cephalins, which are also referred to as phosphatidic acids and represent derivatives of 1, 2-diacyl-syn-glycerol-3-phosphoric acids. By contrast, phospholipids are usually understood as meaning mono- and, preferably, diesters of phosphoric acid with glycerol (glycerophosphates), which are generally considered to be fats. In addition, sphingosines and sphingolipids are also suitable. Such fats, hydrocarbons and waxes can be used in amounts of 0.1 to 99.5 % by wt.

Moreover, known Pearlescent Waxes, Bodying Agents and Thickeners as well as superfatting agents can also be used.
Superfatting agents which can be used are substances such as, for example, lanolin and lecithin, and polyethoxylated or acylated lanolin and lecithin derivatives, polyol fatty acid esters, monoglycerides and fatty acid aikanolamides, the latter also serving as foam stabilizers. Such super fatting agents can be used in amounts of 0.1 to 15 % by wt.
Stabilizers
Stabilizers which can be used are metal salts of fatty acids, such as, for example, magnesium, aluminum and/or zinc stearate or ricinoleate. Such stabilizers can be used in amounts of 0.1 to 10% by wt.
Polymers
Suitable polymers include anionic, zwitterionic, amphoteric, nonionic and cationic polymers. Suitable polymers are, for example, suitable polymers and thickeners are listed in Cosm. Toil. 108, 95 (1993). Such polymers can be used in amounts of 0.001 to 5 % by wt.
Silicone Compounds
Suitable silicone compounds which are volatile or non-volatile, for example, dimethylpolysiloxanes, methylphenylpolysiloxanes, linear and cyclic silicones, and amino-, fattyacid-, alcohol-, polyether-, epoxy-, fluorine-, glycoside- and/or alkyl-modjfjed silicone compounds, which can either be liquid or in resin form at room temperature. Also suitable are simethicones, which are mixtures of dimethicones having an average chain length of from 200 to 300 dimethylsiloxane units and hydrogenated silicates. Such silicone compounds can be used in amounts of 0.1 to 10% by wt.
Biogenic Active Ingredients
Biogenic active ingredients can also be included meaning those which do not arise from the plant Trachyspermm ammi Linn, such as, for example, tocopherol acetate, tocopherol palmitate, ascorbic acid, (deoxy)ribonucleic acid and fragmentation

products thereof, retinol, bisabolol, allantoin, phytantriol, panthenol, menthol, anethol, AHA acids, amino acids, ceramides, pseudoceramides, essential oils, further plant extracts and additional vitamin complexes. Such biogenic active ingredients can be used in amounts of 0.001 to 5.0% by wt.
Deodorants and Antimicrobial Agents
Cosmetic deodorants are also possible ingredients which can be added to counteract, mask or remove body odors. Body odors arise as a result of the effect of skin bacteria on apocrine perspiration, with the formation of degradation products which have an unpleasant odor. Accordingly, deodorants comprise active ingredients which act as antimicrobial agents, enzyme inhibitors, odor absorbers or odor masking agents.
Antiperspirants can also be added in the cosmetic preparation to reduce the formation of perspiration by influencing the activity of the eccrine sweat glands, thus counteracting underarm wetness and body odor.
Suitable astringent antiperspirant active ingredients are primarily salts of aluminum, zirconium or of zinc.
Customary water-soluble additives are, for example, preservatives, water-soluble fragrances, pH regulators, e.g. buffer mixtures, water-soluble thickeners, e.g. water-soluble natural or synthetic polymers, such as, for example, xanthane gum, hydroxyethylcellulose, polyvinylpyrrolidone or high molecular weight polyethylene oxides.
Such deodorant and antimicrobial agents can be used in amounts of 0.001 to 5.0% by wt.
Film Formers
Conventionally the film formers are selected from, for example, chitosan, microcrystalline chitosan, quaternized chitosan, polyvinylpyrrolidone, vinylpyrrolidone - vinyl acetate copolymers, polymers of the acrylic acid series, quaternary cellulose derivatives, collagen, hyaluronic acid and salts thereof, and similar compounds. Suitable film formers can be used in amounts of 0.001 to 5.0% by wt.

Thickeners
Thickeners/ rheology modifiers may also be utilized as part of the cosmetically acceptable carrier of compositions according to the present invention. Amounts of the thickener may range from 0.0001 to 10%, usually from 0.001 to 5%, by weight.
Swelling Agents
The swelling agents for aqueous phases may be montmorillonites, clay mineral substances, Pemulen, and alkyl-modified Carbopol grades (Goodrich). Such additives can be incorporated in amounts of 0.001 to 2.0% by wt.
Hyd rot ropes
To improve the flow behavior, hydrotropes can be added, such as, for example, ethanol, isopropyl alcohol, or polyols, can also be used. Such additives can be incorporated in amounts of 0.1 to 15% by wt,
Preservatives
Suitable preservatives are, for example, phenoxyethanol, formaldehyde solution, parabenes, pentanediol or sorbic acid, and the other classes of substance listed in Annex 6, Part A and B of the Cosmetics Directive. Such preservatives can be incorporated in amounts of 0.001 to 5 % by wt.
Other adjunct minor components may also be incorporated into the cosmetic compositions. These ingredients may include coloring agents, opacifiers, and perfumes. Amounts of these other adjunct minor components may range anywhere from 0.001 % up to 20 % by wt. of the composition.
The details of the invention, its objects and advantages are explained hereunder in greater detail in relation to non-limiting exemplary illustrations as per the following examples:
EXAMPLES:
Example 1 - Extraction of fruits/seeds of Trachvsaermum ammi Linn.

The air-dried fruits/ seeds of Trachyspermm ammi Linn., (200 g) was powdered, extracted with hexane through soxhiet apparatus for about 8 hrs. The dilute extract was concentrated under reduced pressure to get 2.32 g of crude hexane concentrate. The crude hexane concentrate showed reduction in hair growth time by 27%,
Example 2 - Extraction of fruits/seeds of Trachyspermum ammi Linn.
The air-dried fruits/ seeds of Trachyspermm ammi Linn., (700 g) were powdered, extracted with methanol through soxhiet apparatus for about 8 hrs. The dilute extract was concentrated under reduced pressure to get 46.0 g of crude methanol concentrate. The crude methanol concentrate was showed reduction in hair growth time by 13%.
Example 3 - Isolation of Thvmol from hexane extract of T. ammi Linn.
The hexane concentrate of T. ammi (5g) was dissolved in chloroform and adsorbed on silica gel (100-200 mesh, 9g). 147g of silica gel (100-200 mesh) was packed in glass column followed by loading the adsorbed silica gel which was then eluted with chloroform, chloroform : ethyl acetate (9:1, 8:2) and finally with ethyl acetate. Total of 40 fractions were collected, homogeneous fractions were combined based on TLC profile and divided into three major fractions, Fr, A (0.34g), Fr. B (3.57g) and Fr. C (0.57g). The fraction B was further purified by small silica gel column using hexane: chloroform:: 1:1 as an eluent to get pure compound, l.Bg which was light yellow colored liquid at room temperature. The compound was crystallized at low temperature. The compound was identified as thymol based on physical and chemical data (NMR spectral data and GC data). The compound was investigated for hair growth property where it showed 37% reduction in hair growth completion time.
Example 4 - Extraction and isolation of B-Asarone from rhizomes of Acorus calamus Linn.
The air-dried rhizomes/ roots of Acorus calamus Linn., (650 g) were crushed into small pieces and extracted with hexane through soxhiet apparatus for about 8 hrs. The dilute extract was concentrated under reduced pressure and 54 g of crude hexane concentrate was obtained. The major compound separated by column

chromatography and it was identified as B-asarone from its spectroscopic data. The compound, B-asarone was showed hair growth reduction time by 10 %.
Example 5 - Extraction of flower buds of Syzyaium aromaticum Linn.
The air-dried flower buds of Svzvaium aromaticum Linn., (Clove, 100 g) were crushed and extracted with hexane through soxhlet apparatus for about 8 hrs. The dilute extract was concentrated under reduced pressure to obtain 3.31 g of crude hexane concentrate. The crude concentrate contained eugenol (85%) which showed reduction in hair growth time by 10%.
Thus p-asarone and the phenolic compound, eugenol, as actives did not demonstrate any significant hair growth promoting activity. Even though eugenol is structurally related to anethole of US 6203782 mentioned in the background art, it showed a markedly different activity unlike anethole in not showing any significant hair growth promoting activity.
Example 6- Animal experimentation
This example demonstrates the method of hair growth property of the specially preferred concentrates / fractions/ compounds / formulations of the invention by estimation of time reduction of hair growth.
Experimental Protocol: Female Wistar rats weighing 120-150 gm were used for the study. The animals were maintained in a clean cage and were provided with food and water ad libitum. The floor mat husk in each cage was removed and laid afresh on daily basis.
The hair on the dorsal portion of the body of each animal was depilated using a standard, commercially available depilatory cream. After removal of the hair, the skin was cleaned with distilled water and wiped with surgical spirit. Four centimeter square area in the depilated dorsal skin was marked with permanent ink marker. The animals which showed any skin irritant response to the depilatory were removed from the experiment and new animal was replaced.

The experimental animals were divided into 3 groups of 6 animals each. Group 1 animals were served as negative control without any treatment. The negative control comprised of the vehicle for application (only) without having any active compound or extract. To the Group 2 animals, 50 micro liters of 2% Minoxidil (commercially available) was applied in the pre defined area. To the Group 3 animals, the Test samples (extract/ fractions/ pure compound/ s) prepared in liquid paraffin at 2% was applied. The quantity of the extract used for the experiment was 50 micro liters per 4 cm sq area per animal. The application of the Minoxidil and the test samples were continued for 30 days. The observations such as hair growth initiation time in days and hair growth completion time in days were recorded for all the animals on daily basis. The hair growth initiation time was defined as the presence of new hair in the treated site of 4 cm sq area. The hair growth completion time was defined as completing filling of hair in the treated site of 4 cm sq area in each animal which become indistinguishable from the adjacent untreated portion of the body. The average of hair growth initiation time and hair growth completion time was calculated for each group along with control animals. The untreated control for hair growth initiation time (HGIT) is 10 days and hair growth completion time {HGCT) is 30 days. The percentage reduction in hair growth completion time (% Reduction in HGCT) for the treatment is calculated by the formula given below and recorded in Tables 3, 6 and 9,







It is thus concluded from the above tables that the crude concentrate In solvent hexane is much more effective in promoting hair growth than the crude in methanol which reduces the hair growth completion time {HGCT). It is also noteworthy that the active thymol/ carvacrol when administered as a 2% solution in the hair depilated region of Female Wistar rats shows 37 % reduction in HGCT as compared to 47 % in the case of much popularly known and marketed Minoxidil, administered similarly as a 2% solution.
Thus the present invention provides for the desired dermopharmaceutical /cosmetic composition for external application in promoting/ enhancing/ stimulating hair growth or preventing hair loss and methods for making the same. More specifically, the present invention is directed to serve the much desired need for hair care actives/ formulations which would serve as more efficacious, safe to apply and cheap hair growth promoting agent with better consumer acceptance. Importantly, the present invention thus favours in obtaining a hair care agent where the actives of the above said Formula 1 and Formula 2 are either preferably obtained from safe and renewable sources, such as Ex. Trachyspermum ammi Linn., Origanum vulgare Linn., Thymus vulgare or obtained as pure compound (via., Synthesis or isolation from appropriate extract) that can be used either singly or in combination with a cosmetically/ dermopharmaceutically acceptable vehicle.

WE CLAIM:
1. A cosmetic/ dermopharmaceutical composition comprising a hair growth
promoting/ stimulating/ enhancing or preventing hair loss agent comprising an
effective amount of phenolic active compounds/ or its derivatives of Formula 1.

Wherein
R1 represents H or alkyl or C (O)-alkyl
R2 represents C1-C6 Linear/ branched alkyl
R3 represents H, C1-C6 Linear/ branched alkyl
2. A cosmetic/ dermopharmaceutical composition as claimed in claim 1, wherein
said phenolic active compound of Formula 1 is selected from one or more of
phenolic compounds such as Thymol and Carvacrol of Formula 2.

3. A cosmetic/ dermopharmaceutical composition as claimed in any of the
preceding claims wherein the said actives of Formula 1 preferably selected
from Thymol and Carvacrol of Formula 2 are derived via., Synthesis or from
plant extracts.

4. A cosmetic/ dermopharmceutical composition as cfaimed in any of the preceding claims wherein the active comprises of the said phenolic compound of Formula 1, preferably selected from thymol and carvacrol are isolated from appropriate plants. Ex. Trachyspermum ammi Linn., Origanum vuigare Linn., and Thymus vuigare for thymol and Origanum vuigare Linn, for carvacrol.
5. A dermopharmaceutical / cosmetic composition for topical use comprising an effective amount of hair growth promoting agent as claimed in anyone of the preceding claims
and
a cosmetically/ dermopharmaceutically acceptable vehicle with or without other skin/ hair care benefiting agents.
6. A dermopharmaceutical/ cosmetic composition for topical use as claimed in
claim 5 comprising an effective amount of hair growth promoting actives from
extracts/ concentrates from appropriate plants including fruits/ seeds
preferably a methanol extract / concentrate or more preferably a hexane
extract / concentrate
and a cosmetically/ dermopharmaceutically acceptable vehicle with or without other skin/ hair care benefiting agents.
7. A dermopharmaceutical/ cosmetic composition for topical use as claimed in
Claim 5 comprising
a) 0.0001 wt. % to 20 wt. %, preferably 0.001 wt. % to 10 wt. % and more
preferably 0.01 wt. % to 5 wt. % of the said hair growth promoting agent
and
b) a cosmetically/ dermopharmaceutically acceptable vehicle with or without
other skin/ hair care benefiting agents.
8. A dermopharmaceutical/ cosmetic composition as claimed in anyone of claims
5 to 7 comprising a cosmetic composition for topical / externa! use in the form
of products such as creams, ointments, emulsions, gels, lotions, oils, sticks,

sprays, packs, wraps, woven or non-woven wipes, films or patches and the like as a vehicle of the said hair growth composition.
9. A dermopharmaceutical /cosmetic composition as claimed in anyone of claims
5 to 8 wherein the said hair growth promoting agent comprises selectively
any one or more of (a) pure compound of Formula 1 preferably selected from
thymol and carvacrol of Formula 2; (b) an extract/ concentrate of an
appropriate natural source material comprising the said compounds of
Formula 1 preferably thymol and carvacrol of Formula 2; and (c ) any
natural source material comprising anyone or more of the said active
compounds thymol and carvacrol of Formula 2.
10. A cosmetic composition comprising a hair growth promoting agent comprising
one or more phenolic compounds of Formula 1 as an active ingredient in
effective amounts and a dermopharmaceutical composition obtained thereof
substantially as herein described and illustrated with reference to the
accompanying examples.