FIELD OF THE INVENTION

The present invention relates to a hair care agent favouring hair growth promotion/ stimulation/ enhancement or prevention of hair loss and a cosmetic/ dermopharmaceutical composition comprising the same in effective amounts adapted for external application thereby promoting or enhancing or stimulating hair growth or preventing hair loss. More particularly, the said hair growth promoting / stimulating/ enhancing or preventing hair loss agent comprises steroidal triterpene compounds or its derivatives that may be present in combination with a cosmetically/ dermopharmaceutically accepted vehicle with or without other skin / hair care benefit agents in the cosmetic/ dermopharmaceutical composition. The invention includes a dermopharmaceutical composition suitable for external application in promoting or enhancing or stimulating hair growth or preventing hair loss.. The invention particularly relates to steroidal triterpene compound as the active ingredient of Formula 1 represented hereunder

Wherein
R represents OH, OAc or O

More specifically, the present invention provides simple and cost effective hair care benefiting agents comprising steroidal triterpene active compounds selected from cyclomusalenone 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 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 fall.

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.

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 glycosaminoglycanase 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 glycosaminoglycanase 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.

Another US patent 6, 482, 857 discloses a suitable composition containing triterpenes for regulating hair growth, involving triterpenes such as lupane triterpenes, derivatives of lupane triterpenes, derivatives of oleanane triterpenes, derivatives of ursane triterpenes, and salts and mixtures thereof.

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 B5 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.

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.

It is clearly apparent from the above existing state of the art and subsequent discussions thereunder that it is imperceptible to draw a structure-activity relationship of the behavioral aspects of compounds promoting hair growth and hence 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

Thus the primary object of the present invention is to provide for a hair growth promoting agent that would be safe and compatible as hair care active.

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 agents.

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 from renewable materials such as plants.

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 the said identified plant sources favouring 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 for hair care formulations comprising hair growth compositions from safe plant sources extracts bearing actives possessing good skin / hair 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 hair care agent favouring hair growth promotion/ stimulation/ enhancement or prevention of hair loss comprising anyone or more of steroidal triterpene derivatives of Formula 1 hereunder

Wherein

R represents OH or OAc or O

In another preferred aspect of the present invention there is provided a hair care agent comprising said steroidal triterpene derivative, cyclomusalenone or 31-norcyclolaudonone of Formula 2 as an effective hair growth promoting/ stimulating/ enhancing or preventing hair loss active as hereunder Importantly, in keeping with the requirement to explore new hair care agents with hair growth promoting/ enhancing/ stimulating or preventing hair loss characteristics and since it is impossible to draw a structure-activity relationship to the behavioral aspects of compounds showing hair growth promoting effect, It has surprisingly been found that the above said steroidal triterpene active meet the much desired criteria of a superior hair care agent by way of said hair growth promoting/ enhancing/ stimulating or preventing hair loss which is found to be simple in effecting the hair growth under low effective concentrations, cost effective and safe in having less or no side effects in association to the hair growth enhancing/ stimulating or preventing hair loss.

Also, efforts were further directed to provide said selective compounds of Formula 1 and 2 revealing the hair growth promoting/ enhancing/ stimulating or preventing hair loss sourced from natural renewable material such as plants and according to yet another aspect of the invention there is provided a hair growth agent wherein the said agent comprises said steroidal triterpene compound of Formula 1 or preferably of Formula 2 as extracts / concentrates from appropriate plant sources of genus Musa preferably Musa paradisiaca or extracts/ concentrate from the said plant containing cyclomusalenone of Formula 2 as atleast one ingredient as the hair care active in methanol or more preferably in hexane.

Advantageously, the above extract/ concentrate of the selective compound of formula 1 and 2 sourced from M. paradisiaca showing promoting /enhancing / stimulating growth of hair or preventing hair loss in accordance with the present invention surprisingly is in substantial deviation from its known characteristics / biological properties. Importantly, this was in substantial deviation from the well known several biological properties of the extracts from various parts of the plant body as on record such as; two new antiulcerogenic sterylglucosides- sitoindosides I and II were isolated from the fruits of M. paradisiaca (Ghosal et. al., J. Chem. Res. Synop. 1984, 110, 965-975). The fruit of M. paradisiaca contains large amounts of two physiologically important compounds, serotonin nad norepionephrine. Serotonin inhibits gastric secretion and stimulates smooth muscle in the intestine and elsewhere. The therauptic uses of the fruit (in celiac disease, constipation, peptic ulcer etc.) may be due to the presence of these active principles. (Waalkes et al., Science, 1958, 127, 648). The skin and pulp of the green fruit of M.paradisiaca contain anti-fungai substances while the ripe one contain both anti-fungal and anti¬bacterial substances (The Wealth of India, raw materials, 1995, Vol. VI, 448). An antiulcer active flavonoid leucocyanidin, was reported from the unripe fruit of M. paradisiaca (Lewis et al., J. Ethnopharmacol., 1999, 65, 282-288). The methanolic extract of the fruit was reported to have anti-oxidant effect (Goel et al., Indian J. Expl. Biology, 2001, 39, 719-22). The flower extract showed antibacterial activity against Micrococcus pyogenes var. aures and reported diglycosides of delphinidin and cyanidin (The Wealth of India, raw materials, 1995, Vol. VI, 448).

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 care agent and in this respect the hair care agent of the present invention involving the steroidal triterpenes of Formula 1 and preferably of Formula 2 are found to be significantly efficacious 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.

According to another aspect of the present invention there is provided the said hair care agent wherein the said actives are selected from anyone or more of steroidal triterpenes of Formula 1 or preferably cyclomusalenone of Formula 2 either obtained via synthesis or from plant extracts.

According to another preferred aspect of the present invention there is provided the said hair care agent selected from one or more of triterpene derivatives of formula 1 or preferably cyclomusalenone of formula 2 as extracts/ concentrates from plant Musa paradisiaca or its related species; or as extracts/ concentrates from the said plant containing cyclomusalenone of formula 2 as atleast one ingredient in methanol extract or more preferably in ethyl acetate extract; or any plant material sourcing such said actives of Formula 1 or Formula 2.

According to yet another preferred aspect of the present invention there is provided the said hair care agent wherein the hair growth promoting active comprises extracts from plant parts preferably selected from flowers, stems and fruits of the plants of

Musa paradisiaca including its variants and containing cyclomusalenone of formula 2 as at least one of its secondary metabolites.

In another aspect of the present invention there is provided a cosmetic and/ or demopharmaceutical composition for topical use comprising an effective amount of said hair care agent in combination with a cosmetically/ demopharmaceutically acceptable vehicle with or without other skin benefitting agents.

In yet another preferred aspect of the present invention there is provided a cosmetic and/ or demopharmaceutical composition for topical use comprising an effective amount of said hair care agent of Formula 1 or preferably Formula 2 obtained either synthetically and/ or from extracts/ concentrates from the plant Musa paradisiaca and preferably from the said select plant part such as flowers, stems, seeds and fruits preferably as a methanol extract/ concentrate or the plant material itself and a cosmetically/ dermopharmaceutically acceptable vehicle with or without other skin/ hair care benefiting agents.

In another preferred aspect of the present 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 care agent and

b) a cosmetically/ dermopharmaceutically acceptable vehicle with or without other skin/ hair care benefiting agents.

In yet another preferred aspect of the present invention there is provided the said dermopharmaceutical/ cosmetic composition comprising a cosmetic composition for topical / external use in the forms including oils, creams, ointments, emulsions, gels, lotions, sprays, packs, wraps, woven or non-woven wipes, films or patches and the like as a vehicle of the said hair growth composition.

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

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.

DETAILED DESCRIPTION OF THE INVENTION

As discussed hereinbefore, the present invention provides for a hair care agent comprising anyone or more of steroidal triterpene derivatives of Formula 1 and preferably cyclomusalenone of Formula 2 as hereunder and cosmetic and /or dermopharmaceutical composition for topical use comprising the same in effective amounts. The said composition may contain a single compound or mixture of compounds as extracts or pure compounds as hair care active.. The invention is further related to a process of producing said hair care compositions involving a selective combination of said hair care/ growth promoting actives or pure compounds/ agents with or without other carriers/ hair care additives sourced from plants of genus Musa preferably (Ex. Musa paradisiaca Linn.) and also relates to processes for sourcing the said actives from said selective plant material. Accordingly the present invention provides hair care agent with growth promoting / stimulating/ enhancing or preventing hair loss characteristics comprising anyone or more actives of general Formula 1


Wherein
R = OH or OAc or O
In accordance with an exemplary and non-limiting embodiment, the said steroidal triterpene active is preferably selected from cyclomusalenone of Formula 2 as hereunder.

A further aspect of the invention is based upon the selective and surprising finding that active selected from cyclomusalenone of Formula 2 derived from the plants can provide for cosmetic composition possessing hair growth characteristics that showed excellent hair growth promoting/ 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 active 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 of genus Musa preferably (Ex. Stem or fruits or flowers of Musa paradisiaca Linn). The extract or concentrate is preferably in methanol or more preferably in hexane containing steroidal triterpene compound of 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. Musa paradisiaca 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 comprising the same for topical use, and a process for producing the said composition either by isolation from natural sources, as a single entity pure compound of Formula 2 or anyone of the actives of Formula 1 as a semi pure mixture of compounds of Formula 1 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 of genus Musa preferably (Ex.. paradisiaca 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 M. paradisiaca Linn., of the invention comprises their extraction from stem / flowers, 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 compounds and compositions of the present invention 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/ dermopharmaceutically 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 present 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-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.

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 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 phosphatide 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 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 Musa paradisiaca 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, quatemized 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.

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.

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 flowers of Musa paradisiaca Linn.

The air-dried flowers of M. paradisiaca Linn., (55g) was powdered, extracted with hexane through soxhlet apparatus for about 8 hrs. The dilute extract was
concentrated under reduced pressure to get 4g of crude hexane concentrate. The crude hexane concentrate showed good hair growth promotion by in-vitro cell line assay (2.56@10ug/ml).

Example 2 - Extraction and isolation of active compound from flowers of M. paradisiaca Linn.

The air-dried flowers of M. paradisiaca Linn., (600 g) were powdered, extracted successively with hexane followed by methanol through soxhlet apparatus for about 8 hrs. The dilute extracts were concentrated under reduced pressure to get 9 g and 43 g respectively. The crude methanol concentrate was fractionated with chloroform and n-butanol to get corresponding fractions, 8g and 11 g respectively. The initial hexane extract and chloroform fraction showed similar spots on TLC plate, then combined both hexane extract and chloroform fraction to get 17 g. The combined extract was adsorbed on the silica gel (70, 60-120 mesh) and loaded on the glass column. The column was eluted with mixture of hexane: ethyl acetate (99.5: 0.5, 99:1, 98:2) and combined homogeneous fractions based on TLC pattern. The initial three fractions were combined, obtained 2.5g (Fr.l), fractions 4-6 were combined to get 400mg (Fr.2), fractions 7-8 were combined to get 55mg (Fr.3), fractions 9-16 were combined to get 550 mg (Fr.4), fractions 17-25 were combined to get 107 mg (Fr.5), fractions 26-28 were combined to get 8.3g (Fr.6). Fraction 6 has been submitted for hair growth studies and showed good hair growth property. The active fraction was repeatedly chromotographed over silica gel columns eluted with hexane: ethyl acetate and finally obtained solid compound which was re-crystallized with ethyl acetate to get colorless needles, [285 mg, mp: 120-25°C, Rf 0.59 (Hexane: ethyl acetate 8:2)]. The compound is the preferred compound of Formula 2 of the present invention.

The UV (CHCI3) spectrum shows a λ ,max absorbance value at 215nm.

The IR spectrum values are at 1709cm"1 and other characteristic signals; Proton (1 H) NMR main peaks in CDCI3 are at: 5 0.39 (1H, d, J=4.0Hz), 0.61 (1H, d, J=4.0 Hz), 0.87 (3H, d, J=6.3Hz), 0.9 (3H, s), 0.99 (3H, d, J=6.2Hz), 1.00 (3H, s), 1.01 (3H, d, J= 5.7Hz), 1.64 (3H, s), 4.67 (2H, s); Carbon (13C) NMR values in CDCI3 are at: 510.73, 17.88, 18.31, 18.60, 19.14, 20.14, 24.84, 25.18, 25.88, 26.96, 27.17,
28.03, 29.68, 31.43, 32.77, 32.84, 33.88, 35.39, 35.98, 40.98, 41.59, 45.30, 46.00, 47.06, 48.75, 49.97, 52.17, 109.37, 150.16, 213.38.

Example 3: Hair growth evaluation in Hacat cells

This example demonstrates the method of hair growth property of the specially preferred extracts / fractions/ purified compounds of the invention by measurement of HaCat cell line proliferation, by MTT assay.

Experimental Protocol: HaCat cell culture:

HaCat cells were cultured in Dulbecco's modified Eagle's medium supplemented with 2 mM L-glutamine, 1 -x antibiotic solution like Penicillin and streptomycin solution along with 10 % fetal bovine serum at 37 °C, in a 5% C02 incubator.

Thiozolyl Blue [3-(4, 5-Dimethylthiazol-2-yl)-2,5-Diphenyl Tetrazolium Bromide] (MTT) Assay:

HaCaT cells at lx 104 cells/well were seeded into per well of 96-well plate, cultured for 24 h in DMEM, supplemented with 0.5% fetal bovine serum. The cells were treated either vehicle or Minoxidil (0.1 uM) along with various concentrations of plant crude, their fractions as well as the purified compound at various molar concentrations, followed by 72 h of incubation at 37°C, in a 5% C02 incubator. To check the proliferation of the cells, twenty microliters of MTT solution (5 mg/ml) was added per well and incubated for 3 h at 37°C in the dark. The supernatant was then removed, and the formazan crystals were dissolved in 200 μ 1 of DMSO. The samples were incubated for 30 min at room temperature or until complete solubilization of formazan crystals, and quantified by measuring optical density at 570 nm using a spectrophotometer. Results are expressed as percentage change with respect of only cells. Experiments were performed 4 times and the average values were recorded. Table 1 summarizes the hair growth activity of the active compound along with control compound.

Example 4- 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 Table 4.

It is thus concluded from the above tables that the pure compound, cyclomusalenone is much more effective in promoting hair growth than the control minoxidil in cell lines. It is also noteworthy that the active cyclomusalenone when administered as a 2% solution in the hair depilated region of Female Wistar rats shows 53 % reduction in HGCT as compared to 50% in the case of much popularly known and marketed Minoxidil, administered similarly as a 2% solution.

Thus the present invention provides for a hair care agent and the desired dermopharmaceutical /cosmetic composition for external application obtained thereof 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 efficacious, safe to apply and cheap hair growth promoting agent with better consumer acceptance.

WE CLAIM:

1. A hair care agent favouring hair growth promotion/ stimulation/ enhancement or prevention of hair loss comprising anyone or more of steroidal triterpene derivatives of Formula 1 hereunder

Wherein

R represents OH or OAc or O

2. A hair care agent as claimed in claim 1 comprising steroidal triterpene derivative, cyclomusalenone or 31-norcyclo-laudonone of Formula 2 as an effective hair growth promoting/ stimulating/ enhancing or preventing hair loss active as hereunder

3. A hair care agent as claimed in any one claims 1 or 2 wherein the said actives are selected from anyone or more of steroidal triterpenes of Formula 1 or preferably cyclomusalenone of Formula 2 obtained either via synthesis or from plant extracts.

4. A hair care agent as claimed in any of the preceding claims wherein the agent is selected from one or more of triterpene derivatives of formula 1 or preferably cyclomusalenone of formula 2 as extracts/ concentrates from plant belonging to genus Musa, preferably Musa paradisiaca or its related species; or as extracts/ concentrates from the said plant containing cyclomusalenone of formula 2 as atleast one ingredient in methanol extract or more preferably in ethyl acetate extract; or any plant material sourcing such said actives of Formula 1 or Formula 2.

5. A hair care agent as claimed in anyone of claims 1 to 4 wherein the hair growth promoting active comprises extracts from plant parts preferably selected from flowers, stems and fruits of the plants of Musa paradisiaca including its variants and containing cyclomusalenone of formula 2 as at least one of its secondary metabolites.

6. A cosmetic and/ or demopharmaceutical composition for topical use comprising an effective amount of hair care agent as claimed in anyone of claims 1-5 in combination with a cosmetically/ demopharmaceutically acceptable vehicle with or without other skin benefitting agents.

7. A cosmetic and/ or dermopharmaceutical composition for topical use as claimed in claim 6 comprising an effective amount of hair care agent of formula 1 or preferably Formula 2 obtained either synthetically and/ or from extracts/ concentrates from the plant Musa paradisiaca and preferably from the said select plant part such as flowers, stems, seeds and fruits preferably as a methanol extract/ concentrate or the plant material itself and

a cosmetically/ dermopharmaceutically acceptable vehicle with or without other skin/ hair care benefiting agents.

8. A dermopharmaceutical/ cosmetic composition for topical use as claimed in Claims 6 and 7 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 care agent and

b) a cosmetically/ dermopharmaceutically acceptable vehicle with or without other skin/ hair care benefiting agents.

9. A dermopharmaceutical/ cosmetic composition as claimed in anyone of claims 5 to 8 comprising a cosmetic composition for topical / external use in the forms including oils, creams, ointments, emulsions, gels, lotions, sprays, packs, wraps, woven or non-woven wipes, films or patches and the like as a vehicle of the said hair growth composition.

10. A dermopharmaceutical /cosmetic composition as claimed in anyone of claims 5 to 9 wherein the said hair care agent comprises selectively any one or more of (a) pure compounds of Formula 1 preferably selected from cyclomusalenone of Formula 2; (b) an extract/ concentrate of an appropriate natural source material comprising said compounds of Formula 1 preferably cyclomusalenone of Formula 2; and (c) any natural source material comprising anyone or more of the said active compounds of Formula 1 or preferably cyclomusalenone of Formula 2.

11. A hair care agent comprising one or more of steroidal triterpene compounds of Formula 1 and a cosmetic/dermopharmaceutical composition comprising the said active in effective amounts substantially as herein described and illustrated with reference to the accompanying examples.