FIELD OF THE INVENTION

The present invention relates to a cosmetic or pharmaceutical composition, especially dermatological composition, comprising an effective amount of at least one active compound of Formula 1 represented hereunder, intended in particular for promoting or enhancing or stimulating the growth of hair along with cosmetically/ dermopharmaceutically accepted vehicle with or without hair care benefiting agents.

Formula 1

Wherein

R =COOH (Nardin), CHO (Nardal), CH2OH, COOR', CONR1R2 groups;
R'=C1-C22 alkyl, hydroxyl alkyl, benzyl or substituted benzyl groups.
R1= R2—H, R

Specifically, the invention relates to a simple and cost effective dermopharmaceutical composition for external application in promoting or enhancing or stimulating hair growth comprising the hair care benefiting agent such as Nardin of Formula 2 which can be used as such or in the form of derivatives such as esters, amides or its salts along with a dermatologic ally acceptable vehicle.

Nardin; Formula 2
its salts and/ or derivatives thereof.

Most importantly, the said hair care benefit agent comprising anyone or more of the said Nardin of Formula 2, its analogs and derivatives can be sourced from safe and renewable plant source, Nardostachys jatamansi DC which can be used singly or in combination with cosmetically/ dermopharmaceutically acceptable vehicle/ carriers.

BACKGROUND OF THE INVENTION

Hair growth and better hair coverage are the long felt needs of every human being who suffer from hair fall/ loss problem. The other unmet needs are reduction in hair fall and hair thinning. Decreased hair growth in length is also another common problem seeking attention.

The hair fall or decrease in hair density could be due to several reasons. Aging, scalp infections, post effect of certain diseases such as typhoid, jaundice, malaria, hormonal imbalance, conversion of testosterone to 5-alpha dihydrotestosterone, reduction in anagen hair either due to anagen or telogen effluvium are know to contribute to hair fall/ loss problem. Poor nutrition and other general physiological reasons are also known to contribute to the hair fall/ loss problem. Autoimmune disorders do play a role as in the case of alopecia.

Several attempts have been made to develop/invent medicaments to address this 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 the fine hair formation. With the onset of 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.

The other important approach available for the problem is hair transplantation through surgical method. The natural (autologus in the case of natural) or synthetic hair fibers are weaved into the scalp at equidistance. This treatment is not only expensive but also requires continuous maintenance therapy. Further, this method also will not offer hair growth or reduction in hair fall.

Therefore, there remains a need 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 and treatments for alopecia in order to enhance the effects of such treatments on hair growth.

Several active ingredients/ extracts have been reported for hair growth property. These are glyceride pentadecanoate, cepharanthin, Swertia extract liquid, soluble cysteine, ginseng extract liquid, glycyrrhetinic acid, tocopherol aceate, hinokitol, capsicum tincture, sweet grass extract, nicotinamide, salicylic acid (Nomura M, U. S. Patent. 5,750,107). Some nitrogen containing molecules, like minoxidil and cantharidin are commonly used ingredients in formulations for promoting or stimulating the hair growth (Bonte F et. al., U. S. Patent, 5, 607, 693). Some of these materials are showing side effects.

Some hair growth promoters in the prior art include an active ingredient extracted from plants. For example, prior investigators have proposed using extracts from the Orchidaceae species, Bletilla striata, and from plants of the Mefiaceae and Lamiaceae families in hair growth promoters (Japanese patent JP 1038012, Japanese patent JP 5155738; and Kobayashi, et al., Yakugaki Zasshi, 1993, 113, pp.718-724).

Therefore, the above said existing state of the art clearly reveals that on one hand there is a need for newer, effective and safe hair growth promoters harnessed from a natural source which promote activation of the hair root, facilitate hair growth, strengthen hair and are safe to use on the skin and on the other there is a need for processes to obtain a selective active extract.

The above existing state of the art and subsequent discussions therein clearly reveals 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 and cost effective in promoting the activation of hair root, facilitate growth and strengthen hair and are safe to apply on the skin in having less or no side effects with the desired hair growth promoting effect.

OBJECTS OF THE INVENTION

It is thus the basic object of the present invention to provide for hair growth promoting or stimulating agent that would be safe and compatible to the skin as hair care active agent.

Yet another object of the present invention is directed to a hair growth promoting formulation including cosmetic or dermatological composition containing the said hair care agent in an effective amount along with an acceptable vehicle with or without hair benefiting agent that would promote the growth of hair for catering to the needs of various people.

Yet another object of the present invention is directed to a hair growth agent and/or formulations thereof which can be sourced from either synthetic or natural sources simply and cost-effectively for variety of hair care applications/ formulations and the like.

A further object of the present invention is directed to identification of hair care benefiting agents from plant source and to processes of extraction of selective hair care actives from plant sources especially directed to favouring hair growth promoting /stimulating/ enhancing effect.

Still another objective of the present invention is to provide hair growth promoting / enhancing / stimulating composition comprising of selective plant extract actives/ derivatives thereof as one of the hair growth promoting/ enhancing/ stimulating agent/s.

A still further object of the present invention is to direct the preparation of hair care formulations including hair growth composition involving extracts/ actives from safe and renewable plant sources that would favour good hair and/ or skin compatibility.
S
UMMARY OF THE INVENTION

Thus according to the basic aspect of the invention there is provided a cosmetic/ dermopharmaceutical composition comprising a hair growth promoting/ stimulating/ enhancing agent comprising an effective amount of compound of Formula 1

Formula 1

Wherein
R = COOH (Nardin), CHO (Nardal), CH2OH, COOR', CONR1R2 groups;
R'-C1-C22 alkyl, hydroxyl alkyl, benzyl or substituted benzyl groups.
R1= R2=H,R'

In another aspect of the invention there is provided a cosmetic/ dermopharmaceutical composition wherein said hair growth promoting agent comprises an active nardin of

Formula 2.

Nardin; Formula 2
its salts and/ or derivatives thereof.

Importantly, in keeping with the requirement for a hair care agent that can be sourced simply and cost-effectively from safe and renewable plant sources, the present invention thus lead to a surprising finding, that the selective active Nardin and derivatives of Formula 1 sourced from the plant Nardostachys jatamansi DC could achieve hair growth promotion/ enhancement/ stimulation activity. The said selective extract of Nardostachys jatamansi and their active ingredients such as Nardin of Formula 2 displaying a Rf value of 0.48 in chloroform: methanol (9:1) on a pre-coated silica gel thin layer chromatography plate thus favours in promoting/ enhancing /stimulating the growth of hair when present as nardin or in the form of its salts and/ or derivatives thereof.

While there is some disclosure concerning the use of rhizomes of the plant Nardostachys jatamansi DC as an aromatic adjunct in the preparation of medicinal oils, that reported to promote the growth of hair and also impart the blackness (Kirthikar & Basu, Vol. II, 1308) , there has been no clear indications available to the art as to the related indications on the actives in the plant material extract responsible for imparting the hair growth and/or blackness of hair to serve in improving efficacy especially in achieving desired hair growth and accordingly it has not been possible to arrive at any efficient formulation for hair growth involving even the source of Nardostachys jatamansi DC which could serve the much desired purposes of formulating cosmetic/ dermopharmaceutical composition for hair growth characteristics involving such actives sourced from a safe plant source of Nardostachys jatamansi DC that would in turn offer reliable benefit to people.

It is thus been the basic selective finding of the present invention to reach to selective fraction of the extract from the plant Nardostachys jatamansi DC that could achieve the desired efficacy as a stable hair growth promoting/ enhancing/ stimulating or preventing hair loss characteristics by way of the identification and isolation of the said actives under Formula 1 and 2 defined hereinbefore. Importantly, it was found by way of this invention that the compound under Formula 1 and more specifically Nardin of formula 2 was most effective in showing hair growth promoting/ enhancing/ stimulating or preventing hair loss characteristics in the said selective fraction of the extract involving the said active.

In the backdrop of the above it is indeed apparent that the actives of Formula 1 and
2 sourced from said selective fraction of the extract from N. jatamansi DC, were thus surprisingly and selectively efficacious in terms of promoting/ enhancing /stimulating the growth of hair.

According to yet further preferred aspect of the invention there is provided a cosmetic/ dermopharmaceutical composition wherein the said active compound of Formula 1 is preferably selected from nardin of Formula 2 preferably obtained from plant extracts or obtained as pure compounds (via. conversion of nardin into its derivatives such as nardin esters)

According to another aspect of the invention there is provided a cosmetic/ dermopharmaceutical composition wherein the active comprising of said compounds of Formula 1, preferably selected from nardin of Formula 2, is isolated from appropriate plant, Nardostachys jatamansi DC, or as extracts/ concentrate from the said plant containing nardin of Formula 2 as at least one ingredient.

In yet another aspect of the invention there is provided a dermopharmaceutical/ cosmetic composition for topical use comprising an effective amount of said hair growth promoting/ stimulating/ enhancing agent as claimed in anyone of the preceding claims
and a cosmetically/ dermopharmaceutically acceptable vehicle with or without other skin/ hair care benefiting agents.

Preferably, a dermopharmaceutical/ cosmetic composition for topical use is provided comprising an effective amount of hair growth promoting actives from extracts/ concentrates from appropriate plant including rhizomes/roots preferably an organic solvent 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 there is provided a dermopharmaceutical/ cosmetic composition for topical use 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.

Advantageously, there is provided a dermopharmaceutical/ cosmetic composition by way of the present invention comprising a cosmetic composition for topical/ external 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.

In accordance with yet another aspect of the present invention there is provided a dermopharmaceutical /cosmetic composition wherein the said hair growth promoting agent comprises selectively any one or more of (a) pure compound of Formula 1 preferably selected from nardin; (b) an extract/ concentrate of an appropriate natural source material comprising the said compounds of Formula 1 preferably nardin of Formula 2; and (c) any natural source material comprising anyone or more of the said active compound of Formula 1 preferably nardin of Formula 2.

In another aspect of the invention there is provided a dermopharmaceutical/ cosmetic composition wherein the said hair growth promoting agent comprises a selective fraction of the extract preferably from the roots of Nardostachys jatamansi displaying a Rf 'value of 0.48 on a pre-coated silica gel chromatography plate with chloroform: methanol (9:1) as the mobile phase that comprises selectively of any one or more of compounds of Formula 1.

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 or enhancing or stimulating agent in a cosmetic/ dermopharmaceutical composition for topical use.

The invention is further directed to process for producing the said selective combination of hair care/ growth promoting actives or pure compounds/ agent with or without other carriers/ hair care additives involving the selective isolation from a plant part specifically from the roots of Nardostachys jatamansi DC, and to processes for producing and using the said compositions to achieve hair growth promoting or enhancing or stimulating effect.

In accordance with one 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 1

Formula 1

Wherein
R = COOH (Nardin), CHO (Nardal), CH2OH, COOR', CONR’ groups;
R'=C1rC22 alkyl, hydroxyl alkyl, benzyl or substituted benzyl groups.
R1= R2= H, R'

comprising:

a) subjecting a selective source of Nardostachys jatamansi DC, in powder form, to solvent extraction to provide for an extract;

b) removing the solvent from the extract under vacuum to provide for 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 at least an active agent of said
Formula 2.

According to another aspect of the invention, the said cosmetic composition for topical use includes hair growth promoting/ enhancing / stimulating actives comprising extracts/ concentrate from roots of Nardostachys jatamansi DC. The preferable extract/ or concentrate methanolic extract or more preferable hexane extract/ concentrate comprising

Nardin of Formula 2.
Nardin; Formula 2
its salts and/ or derivatives thereof.

The preferable solvents are low polar solvents like: hexane, benzene, toluene etc., and chlorinated solvents like: dichloromethane, chloroform, carbon tetrachloride etc, esters like, methyl acetate, ethyl acetate etc., 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.

In accordance with a preferred aspect of the invention there is provided a process for the extraction and isolation of hair care agent having hair growth promoting or stimulating characteristics of the above said Formula 2 from a source of Nardostachys jatamansi DC, comprising:

a) subjecting the air-dried rhizomes/ roots of Nardostachys jatamansi, in powder form, to extraction with low polar organic solvent, preferably hexane, to provide an extract;

b) removing the solvent from the extract under vacuum to provide for a concentrate;

c) subjecting the concentrate to column chromatography, preferably a silica gel column, using chloroform: hexane (3:1) as eluant and chloroform to provide for fractions;

d) evaluating the fractions for the presence of Nardin by Thin Layer
Chromatographic experiments having Rf: 0.48 in chloroform;

e) pooling the active fractions and concentrating the resulting solution to dryness in-
vacuo to provide for another concentrate showing enrichment in the amount of the active compound of Formula 2;

f) subjecting the enriched concentrate to a process of crystallization/ re-
crystallization and fractional crystallization if necessary, to provide for the compound of the invention.

Accordingly, the invention provides for the said selective compounds as hair growth promoting/ enhancing/ stimulating agent in a cosmetic and or dermopharmaceutical composition for topical use, to process for producing the said composition either by isolation from natural sources, as a single entity or in a semi pure mixture of compounds, to the said compositions comprising to achieve hair growth promoting effect.

In another preferred aspect, the present invention relates to a process for providing a compound isolated from N. jatamansi DC, to be used as active ingredient in the cosmetic compositions of the invention. The process may be devised through isolation procedures from renewable natural resources such as plants. The process for isolating the compound from N. jatamansi DC, of the invention comprises their extraction from roots, 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.

According to another preferred aspect of the invention there is provided a hair care formulation including cosmetic and/or dermopharmaceutical compositions comprising:

a. about 0.0001% to about 20% weight percent of N. jatamansi DC, rhizome/root
extract and/ or active ingredient; and

b. a cosmetically acceptable vehicle.

The amount of the N. jatamansi DC, rhizome or root extract/ concentrate and/ or active ingredient is preferably in the range of about 0.0001 % to about 20 %, more preferably about 0.001 % to 10 %, most preferably 0.01 % to about 5 % of the total amount of the cosmetic or dermatological composition.

The above discussed cosmetic and/ or dermatological composition for topical use can be in the form of leave-on products wherein the delivery system comprises creams, ointments, emulsions, gels, lotions, oils, sticks, sprays, soaps, packs, wraps, woven or non-woven wipes and films as a vehicle for topical application of the said hair growth promoting composition

The ingredients essentially employed in such a composition are emulsifiers, emollients, silicones, antioxidants, sunscreen agents, perfumes, colors, antimicrobial agents, herbal extract/ compounds.

Isolation of active compound or compounds from Nardostachys jatamansi DC:

The plant, Nardostachys jatamansi of the invention is native to India. It is an erect perennial herb, 10-60 cm high, with long, stout, woody rootstock found in the alpine Himalayas at an altitude of 3,000 to 5,000 m. N, jatamansi has an agreeable odour with a bitter aromatic taste and is used as a substitute for valerian roots (Valeriana officinalis Linn). It yields up to 1.9% of a pale yellow essential oil with a pleasant odour, suggestive of patchouli and valerian (The Wealth of India). Nardostachy jatamansi (Valerianaceae), also known as spikenard or Indian nard, native of India wherein the plant is propagated by cuttings of underground parts and some times by seeds.

General Isolation Procedure:

The active compound from N. jatamansi DC, such as Nardin of Formula 2 of the invention is isolated from plants belonging to the genus Valerianaceae. The plant belongs to India and is available in high altitudes.

The extracts to be used according to the invention are obtained from the rhizomes/ roots of the plant belonging to the family, specifically from Nardostachys jatamansi DC, including its variants.

Extraction:

The extracts to be used according to the invention are prepared by customary methods of extraction of the roots the plant. The suitable conventional extraction methods, such as maceration, agitation maceration, remaceration, fluidized-bed extraction, ultrasound extraction, countercurrent extraction, super critical fluid extraction, percolation, repercolation, evacolation, diacolation and solid-liquid extraction (Soxhlet extraction) each of which is known to theiperson skilled in the art and any of which can be used in principle, reference may be made by way of example to Hagers Handbuch der Pharmazeutischen praxis (5.sup.th edition, Vol. 2, pp. 1026 1030, Springer Verlag, Berlin-Heidelberg-New York 1991). Starting material which may be used are fresh or dried roots the plants, which can be mechanically comminuted prior to extraction. In this connection, all commnution methods known to the person skilled in the art are suitable, mention being made by way of example to commnution using a device containing blades.

Solvents which can be used for carrying out the extractions are preferably organic solvents, in particular low molecular weight alcohols, esters, ethers, hydrocarbons, ketones or halogen-containing hydrocarbons with greater or lesser water contents (distilled or undistilled), Particular preference is given to the extraction with methanol, ethanol, propanol, butanol and isomers thereof, acetone, propylene glycols, polyethylene glycols, ethyl acetate, dichloromethane, trichloromethane, and mixtures thereof. The extraction usually takes place at 20 to 140°C, preferably at 50 to 80°C, in particular at the boiling temperature of the solvents or solvent mixtures. In one possible embodiment, the extraction is carried out under an inert gas atmosphere to avoid oxidation of the ingredients of the extract.iThe extraction times are adjusted by the person skilled in the art depending on the starting material, method of extraction, temperature and the ratio of solvent to raw material, etc. After the extraction, the resulting crude extract can optionally be subjected to further customary steps, such as, for example, concentration, fractionation by partitioning between solvents, purification, including different types of chromatography, concentration and/ or decoloration. If desired, the extracts prepared in this way can, for example, be subjected to selective removal of individual uhdesired ingredients. The extraction can be carried out to any desired degree of extraction, but is usually carried out exhaustively.

The present invention encompasses the finding that the extraction conditions and also the yields of the end extracts can be chosen depending on the desired field of use, through deployment of appropriate precise screening techniques, including hair growth promoting screens on animals.

Isolation of the active compound, nardin from the plant N. jatamansi DC:

The process of isolation of active hair growth promoting/ enhancing / stimulating compound from said roots or rhizomes of N. jatamansi DC, was carried out as follows:

a) the air-dried roots / rhizomes of N. jatamansi DC, were coarsely powdered and subjected to extraction with an organic solvent, preferably hexane, to provide for an extract;

b) concentrating the extract in vacuo to provide for a residue;

c) subjecting the residue obtained in step b) above to column chromatography, preferably a silica gel column, using solvents such as hexane as eluents, hexane: chloroform (3:1, 1:1, 1:3), chloroform, and chloroform: methanol (9:1) to provide for fractions, i

d) evaluating the fractions obtained in step c) above for the presence of Nardin by TLC experiments at Rf: 0.48 in chloroform pooling the active fractions and concentrating the resulting solution to dryness in vacuo to provideanother residue showing enrichment in the amount of Nardin.

f) subjecting the residue to a process for crystallization, re-crystallization and fractional crystallization if necessary, to provide the said active compound of Formula 1.

The above isolation process of the invention can 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 compounds of the invention.

The above extracted active compound Nardin and derivatives of Formula 1 more specifically of Formula 2 in association with cosmetically/ dermopharmaceutically accepted vehicles in cosmetic hair care compositions was tested for hair growth characteristics and it showed hair growth promoting/ enhancing/ stimulating activity indicating its role as a hair growth promoter/ enhancer/ stimulator.

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 dermopharmaceutical 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 -Ci3-carboxylic acids with linear or branched C6 -C22-fatty alcohols. Such oily bodies can be used in amounts of O.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 erriulsifiers. 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 C8/is- 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.

Fats, 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 contain 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 lecithin 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 super fatting agents can also be used.

Super fatting 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 alkanolamides, 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 modified 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 same plant, 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 antfmfcrobfaf agents can be used fn amounts of 0.002 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 clay mineral substances, Pemulen, and alkyl-modified Carbopol grades (B F Goodrich). Such; additives can be incorporated in amounts of 0.001 to 2.0% by wt.

Hydrotropes

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. 1

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 ingredients

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 illustrationsias per the following examples:

EXAMPLES:

Example 1 - Extraction of Rhizomes of Nardostachvs jataman si PC.

The air-dried rhizomes (2 Kg) of N. jatamansi DC, were powdered, extracted with hexane through soxhlet apparatus for about 8 hrs. The dilute extract was concentrated under reduced pressure to get 9.4 g of crude hexane concentrate. The crude hexane concentrate showed % reduction in hair growth completion time by 38%.

Example 2 - Isolation of Nardin from hexane extract of N. jatatnansi DC.

The hexane concentrate of N. jatamansi (9.4 g) was dissolved in chloroform and adsorbed on silica gel (100-200 mesh, 9 g). 147 g of silica gel (100-200 mesh) was packed in glass column followed by loading the adsorbed silica gel which was then eluted with hexane and hexane: chloroform (3:1, 1:1) and divided into two major fractions based on TLC profile. Fraction 2 was purified again over small silica gel column using hexane: chloroform (3:1), nardin (0.537 g) was obtained after re-crystallization from hexane: diethyl ether. The compound was identified as nardin based on physical and chemical data (NMR and mass spectral data) and also co-comparison with an authentic sample. The compound was investigated for hair growth property where it showed 24 % reduction in hair growth completion time.

Example 3 - Preparation of Nardin esters

Generally the carboxylic acid esters can be prepared by using various catalysts like sulphuric acid, p-toluene sulphonic acid (PTSA) and dicyclohexaylcarbodiimide (DCC).

a. Preparation of methyl ester:

560 mg of nardin, 20 g of methanol and 420 mg of p-toluene sulphonic acid was taken in a 50 mi of round bottomed flask and refluxed on water bath. After four hours, the reaction mixture was checked by TLC and the reaction was found to be completed. After usual work the product resulted in light yellow colored oil, which was further purified over a small silica gel column followed by impregnated Silver nitrate silica gel column to yield colorless oil, 389 mg (65%). The compound was investigated for hair growth property that showed 17 % reduction in hair growth completion time.

b. Preparation of butyl ester ,

483 mg of nardin, 10 g of n-butanol and 460 mg of p-toluene sulphonic acid was taken in 50 ml of round bottomed flask and refluxed on oil bath. After four hours, the reaction mixture was checked by TLC and the reaction was found to be completed.
After usual work the product resulted in a colorless oil. The oil was purified further over a small silica gel column followed by Silver nitrate impregnated column (silver nitrate impregnated on silica gel) to obtain a colorless oil, 390 mg (65%). The compound was investigated for hair growth property wherein it showed 27% reduction in hair growth completion time.

c. Preparation of dodecyl ester

314 mg of nardin, 319 mg of dodecanol, 276 mg of dicyclohexyl carbodiimide (DCC), 49 mg of dimethyl amino pyridine (DMAP) and chloroform (10ml) was taken in a 50 ml of round bottomed flask and refluxed on water bath. After one hour, the reaction mixture was checked by TLC and the reaction was found to be completed. After usual work the product resulted in light yellow colored oil, which 'was further purified over a small silica gel column followed by impregnated Silver nitrate silica gel column to yield colorless oil, 280 mg (65%). The compound was investigated for hair growth property that showed 17% reduction in hair growth completion time.

d. Preparation of cetyl ester

312 mg of nardin, 379 mg of cetyl alcohol, 271 mg of dicyclohexylcarbodiimide (DCC), 49mg of dimethylamino pyridine (DMAP) and 10ml of chloroform was taken in a 50 ml of round bottomed flask and refluxed on water bath; After one hour, the reaction mixture was checked by TLC and the reaction was found to be completed. After usual work the product resulted in light yellow colored oil, which was further purified over a small silica gel column followed by impregnated Silver nitrate silica gel column to yield a pale yellow colored oil, 200 mg (65%). The compound was investigated for hair growth property that showed 10% reduction in hair growth completion time.

Example 4 - Hair growth evaluation in Animal model

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 m 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 1 and 2.

Formula

Table 1 |

Table 2

Example 5: Preparation of hair care lotion
Table 3

Process for manufacturing the above said formulation:

1. Demineralized/ DM water from Phase A was taken and the carbomer was dispersed carefully without forming lumps and stirred for 30 minutes, finally the pH was adjusted to 4.5 by using TEA.

2. Phase B was added to phase A and stirred well for five minutes.
3. Phase C ingredients were heated at 70-75°C and added to Phase AB and stirred well for 5 minutes. !

4. Phase ABC was cooled to 60°C and this mixture was neutralized by using Phase D and the pH adjusted between 6.5-7.00 and stirred well.

5. Phase ABCD was cooled to 45°C, colors and perfumes of phase E were added and stirred well for another 5 minutes.

It is thus concluded from the above tables that the crude concentrate in solvent hexane is an effective hair growth promoting agent which reduces the hair growth completion time (HGCT) significantly. It is also noteworthy that the active compound, nardin when administered as a 2% solution in the hair depilated region of Female Wistar rats shows 24 % reduction in HGCT as comparedjto 41 % 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 is preferably obtained from safe and renewable sources, such as Ex. Nardostachys jatamansii DC, or obtained as pure compounds (via., conversion of nardin into its derivatives such as nardin esters) that can be used either singly or in combination with a cosmetically/ dermopharmaceutically acceptable vehicle.

It is thus possible by way of the invention to provide for a selective hair growth promoting or stimulating agent sourced from plant Nardostachys jatamansi DC, which would be safe and compatible as a hair care active agent. Importantly, the invention is thus directed to meet the much required simple, cost-effective and safe to apply and use variety of hair care applications/ formulations and the like.

WE CLAIM:

1. A cosmetic/ dermopharmaceutical composition comprising a hair growth
promoting/ stimulating/ enhancing agent comprising an effective amount of compound of Formula 1

Formula 1

Wherein
R =COOH (Nardin), CHO (Nardal), CH2OH, COOR', CONR1R2 groups;
R'=C11-C22 alkyl, hydroxyl alkyl, benzyl or substituted benzyl groups.
R1— R2 = H/ R

2. A cosmetic/ dermopharmaceutical composition as claimed in claim 1, wherein said hair growth promoting agent comprises an active nardin of Formula 2.

Nardin; Formula 2
its salts/ derivatives thereof

3. A cosmetic/ dermopharmaceutical composition as claimed in any of the preceding claims wherein the said active compound of Formula 1 is preferably selected from nardin of Formula 2 preferably obtained from plant extracts or obtained as pure compounds (via. conversion of nardin into its derivatives such as nardin esters).

4. A cosmetic/ dermopharmaceutical composition as claimed in any of the preceding claims wherein the active comprises of said compounds of Formula 1, preferably selected from nardin of Formula 2, is isolated from appropriate plant, Nardostachys jatamansi DC or as extracts/ concentrate from the said plant containing nardin of Formula 2 as at least one ingredient.

5. A dermopharmaceutical / cosmetic composition for topical use comprising an effective amount of hair growth promoting/ stimulating/ enhancing 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 plant including rhizomes/ roots preferably an organic solvent 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 Claims 5 and 6 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/ external 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 nardin; (b) an extract/ concentrate of an appropriate natural source material comprising the said compounds of Formula 1 preferably nardin of Formula 2; and (c) any natural source material comprising anyone or more of the said active compound of Formula 1, preferably nardin of Formula 2..

10. A dermopharmaceutical/ cosmetic composition as claimed in anyone of claims 5 to 9 wherein the said hair growth promoting agent comprises a selective fraction of the extract preferably from the roots of Nardostachys jatamansi displaying a Rf value of 0.48 on a pre-coated silica gel chromatography plate with chloroform: methanol (9:1) as the mobile phase that comprises selectively of any one or more of compounds of Formula 1.

11. A cosmetic composition comprising a hair growth promoting agent comprising one or more 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.