NZ613331B2 - Monoterpene derivatives of chalcone or dihydrochalcone and their use as depigmenting agents - Google Patents

Abstract

Disclosed are monoterpene derivatives of chalcone or dihydrochalcone corresponding to formula I wherein R1 is H or CH3 and R2 is H or OH, and the use thereof as a depigmenting agent. Also disclosed are cosmetic or dermatological compositions comprising the compounds. The compounds are obtained as an extract of Helichrysum gymnocephalum. extract of Helichrysum gymnocephalum.

Description

MONOTERPENE TIVES OF CHALCONE OR DIHYDROCHALCONE AND THEIR USE AS DEPIGMENTING AGENTS The t invention relates to the use in the field of depigmentation of monoterpene derivatives of chalcone or dihydrochalcone of the formula (I) and plant extracts containing them in cosmetic or dermatological compositions.

R1 = H, Me (I) R2 = H, OH Trihydroxychalcones are disclosed for their depigmenting activity. The position of the OH groups is particularly ant for this activity. 2’,4’,6’—Trihydr0xychalcone (II) shows an ICSO on tyrosinase (monophenoloxidase activity on fungal tyrosinase) of 120 uMl.

O OH O \ _ O HO OH Surprisingly and unexpectedly, the inventors have shown that an additional tution with a terpene or terpineol group (Formula I) greatly enhances this ty. This type of molecule is very seldom found in plants. To date, only three naturally existing compounds represented by the general formula (I) have been disclosed in literature: linderatin (III), linderachalcone (IV) and methyl—linderatin (V).

They have been isolated from: — Piper adzmcum’i leaves, ceac: (-)—methyl—linderatin, — Piper hostmamziamtm var. Berbz'censem1eaves (Piperaccao): (-)—methyl’ linderatin 1000414472 — Lindera umbellaz‘a var. membranaeea""V and lancea“, leavesv" or barksv'”, Lauraceae: (+)—Linderatin, linderachalconeix, methyl-linderatin - Mitrella kentz'z', trunk bark, Annonaceae: (-)-LinderatinX A compound with a closely related structure, gymnochalcone (VI), or alpha-terpineol pinocembrine chalcone, was first isolated by the ors from aerial parts of Helichrysum gymnocephalum (DC) t. methyblinderatin (V) gymnoehalmue (VI) The inventors were also first to isolate linderatin from leaves of Piper aduncum.

With regard to the biological activities described, (-)—1inderatin exhibited cytotoxicity on a cancer cell line x (-)-Methyl-linderatin has in turn an anti-plasmodial ty .

None of the compounds above has been disclosed for their depigmenting ty.

In one aspect, the invention thus provides an extract of Helichrysum gymnocephalum (DC) Humbert enriched with one or more molecules of the following formula (I) ,x/ /\ 9 0H //\//’§\\/t / \ / / HO 0R1 wherein is a single bond or a double bond; R1: H or CH3; and R2 _—. H or OH as a depigmenting agent.

It is preferred that R1 : 1-1. i I Preferably, I | is a double bond, R1 = H and R2 = H or OH, or i is a single bond, R1 =”~ H or CH3 and R2 = H.

More preferably, is a single bond, R1 = H and R2 “ H, that is to say the extract according to the invention is enriched with atin.

More ably, is a double bond, R1 = H and R2 ; OH, that is to say the extract according to the invention is ed with gymnochalcone. Such extract is particularly advantageous since surprisingly, the inventors have found that gyinnochalcone is stable in time therein. In fact, cyclization of chalcones to flavanone, upon addition of a hydroxyl group on 1,4—position in the carbonyl group by a Michael type reaction, which brings about instability of the nes, is not observed in this case.

Such cyclization is observed for the purified gymnochalcone. Thus preferably gymnochalcone will be used in the form of an t of Helichrysum gymnocephalum.

The inventors have shown that such extract of Helichrysum gymnocephalum of the invention is particularly advantageous for its depigmenting activity. The inventors have also shown that such activity is particularly specific of the species zrysum gymnocep/zalum since extracts prepared under the same conditions of Helic/zrysum z‘um, Helichrysum cordifolium and zljysum stoechias, although they all are rich in flavonoids and chalcones, do not exhibit any inhibiting activity for the synthesis of the melanin on 816 murine melanocytes.

Preferably, the extract ing to the invention comprises one or more les of the formula I in an amount of between 0.1 and 30 g, preferably of between 0.1 and 10 g, most preferably ofbetween 0.1 and 5 g, per 100 g of extract solids.

Advantageously, the extract according to the invention originates from aerial parts of Helz'c/zrysum gymnocephalum (DC) Humbert (Asteraceae, syn. Stenoclz'ne gymrzocephala). It is prepared from this plant following traditional steps well known to those skilled in the art.

The aerial parts of ‘c/ziysum gymnocephalum (DC) Humbert may be harvested at 5 different stages of growth of the plant: vegetative stage, pre-flowering stage, onset—of— tlowering stage, flowering stage, fructification stage. Advantageously, the extract according to the invention originates from aerial parts of Helichrysum gymnocephalum (DC) Humbert at the fructification stage, ably at the end of the fication period.

The preferably dried plant is ground before being extracted with an organic solvent which may be an ester (ethyl acetate, isopropyl e), an alcohol (methanol, ethanol, propanol, isopropanol, butanoi), a ketone (methyl ethyl ketone, dimethylketone, methyl isobutyl ketone), a halogenated hydrocarbon (chloroform, romethane), water or a mixture of these ts in any miscible proportion.

The extraction is performed at a plant/solvent ratio of between about 1/1 and about 1/20 and may be repeated 2 to 3 times. The temperature of the extraction solvent may range from room temperature to above ambient, up to the boiling temperature of the solvent involved. The contacting time of the plant with the solvent is from between about 30 min and about 72 hrs.

Then a solid/liquid separation is carried out, wherein the plant is separated from the solvent for example by filtration or centrifugation.

The filtrate obtained may be either: ~ ly taken to dryness by fully evaporating the t, to obtain the final extract, ~ stored as a liquid in the extraction solvent if it is compatible with its intended use. In this case it may be more or less concentrated by an evaporation step, - concentrated. This concentration step to a compound of interest may be carried out by techniques known to the one skilled in the art such as liquid/liquid extraction between 2 non miscible solvents, tion onto a carrier such as silica, an ion—exchange resin, etc. 4472 An extract obtained by extraction, solid/liquid separation followed by drying es mass amount of compound(s) comprised in the formula I of between 0.1 and 30 g, preferably between 0.1 and 10 g, most preferably between 0.1 and 5 g, per 100 g of extract dried material.

If the extract is maintained in a solution, the dried material content of the liquid t is between 0.1 and 80 g per 100 ml.

Another aspect of the invention s to a process for preparing an extract according to the invention.

Another aspect of the invention relates to the cosmetic use of an extract of plant origin enriched with one or more molecules of the following formula (I) or the cosmetic use of a molecule ofthe following formula (I): wherein is a single bond or a double bond; R1 = H or CH3; and R2 = H or OH as a depigmenting agent.

It is preferred that R1 = H.

Preferably, is a double bond, R1 = H and R2 = H or OH, or WDQ-ut is a single bond, R1 = H or CH3 and R2 = H. 2O More preferably, -,*___ is a double bond, R1 = H and R2 = OH, that is to say the ion relates to the cosmetic use of an extract of plant origin enriched with halcone; or to the cosmetic use of the gymnochalcone molecule.

More preferably, is a single bond, R1 = H and R2 = H, that is to say the invention relates to the cosmetic use of an extract of plant origin enriched with linderatin; or to the cosmetic use of the linderatin molecule.

Most preferably, the invention relates to the cosmetic use of an t of plant origin comprising one or more molecules ofthe formula I in an amount of between 0.1 and 30 g, preferably between 0.1 and 10 g, most preferably between 0.1 and 5 g, per 100 g of extract dried material.

Said extract comprising one or more les of the formula (I) is preferably an extract of the invention or an extract of plants belonging to the genus Helic/uysum, Piper, Lindera 0r Mitrella, including: Piper hostmanm’ammz, Piper lzispz‘dum, Piper adzmcum, Lindera aggregate, Lz'ndera umbellata, Lindera glance, la mesnyz', Mz'trella kentii.

Most preferably, linderatin and —linderatin will be used in cosmetics according to the ion in pure form, as synthetized, since they are stable in such form.

On the other hand, preferentially to the cosmetic use of pure gymnochalcone, the cosmetic use of an extract QfHelz'chijVsum gymnocephalum enriched with gymnochalcone will be d since it is more stable therein than in the pure form.

Advantageously, the cosmetic use according to the invention is ed for bleaching and/0r lightening the skin and/or bristles and/or hair, reducing and/or removing age spots from the skin or reducing and/0r removing brownish pigment spots that can be d by UV or chloasma.

The molecules of the formula (1) and/or the plant ts containing them, as a depigmenting agent, have also shown good abilities to control and/or inhibit the production of melanins, which are sible for pigmentation, thereby displaying an advantage in depigmentation of some unaesthetic pigment spots due to hyperpigmentation of the epiderm, especially age spots on skin.

The molecule of the a (1) according to the present invention may be obtained by chemical or biochemical synthesis, or from a plant extract.

It is preferred that the molecule of the formula (I) is selected from the group consisting of: , halcone (Formula VI) wherein i is a double bond, R1 = H and R2 = OH, — linderatin (Formula 111) wherein5 is a single bond, R1 = H and R2 = H, — linderachalcone (Formula IV) wherein is a double bond, R1 = H and R2 = H, ~ methyllinderatin (Formula V) wherein i is a single bond, Rl CH3 and R2 = H. 10004 14472 In the case where the molecule is gymnochalcone, the plant source will preferably be Helichrysum gymnocephalum (DC) Humbert; and more preferably the aerial parts of Helichrysum gymnocephalum (DC) Humbert, and even more preferably the aerial parts of Helichrysum gymnocephalum (DC) Humbert harvested at the fructification stage.

In the case where the le is linderatin, it will preferably be obtained by chemical synthesis.

In the case where the molecule is a linderatin of plant origin, the plant source will preferably be Lindera umbellata var. membranacea and lancea; and more preferably the leaves or barks thereof. r aspect of the invention relates to a cosmetic or dermatological composition comprising, as an active ingredient, an extract of plant origin enriched with one or more molecules of the following formula (I), or one or more molecules of the following formula (I): H’J’A‘ .j‘ff wk iJ II HE) J” on, w‘v‘wlwr is a single bond or a double bond; R1 = H or CH3; and R2 = H or OH.

It is preferred that R1 = H. Preferably, «www.- i is a double bond R1 = H and R2 = H or OH, or - is a single bond, R1 = H or CH3 and R2 = H.

More preferably, is a double bond R1 = H and R2 = OH, that is to say the invention s to a cosmetic or dermatological composition comprising, as an active ingredient: a plant t enriched with gymnochalcone, or the halcone molecule.

More preferably, is a single bond, R1 = H and R2 = H, that is to say the invention relates to a cosmetic or dermatological composition comprising, as an active ingredient: a plant extract enriched with linderatin; or the linderatin molecule.

Most preferably, the invention relates to the cosmetic or dermatological composition of the invention which comprises, as an active ingredient, an extract of plant origin comprising 1000414472 one or more molecules of the a I in an amount of between 0.1 and 30 g, preferably between 0. 1 and 10 g, most preferably between 0.1 and 5 g, per 100 g of extract dried material.

Advantageously, said extract is an extract of the invention or an extract of plants belonging to the genus Helichrysum, Piper, Lindera or Mitrella, including: Piper hostmannianum, Piper hispz'dum, Piper aduncum, Lindera aggregata, Lindera umbellata, Lindera glauca, Mitrella mesnyz'. Mitrella kentiz'.

Another aspect of the invention relates to a dermatological ition according to the ion for use as a medicament. r aspect of the invention s to a dermatological composition according to the invention for use for depigmenting the skin and/or bristles and/or hair.

Another aspect of the invention relates to a dermatological composition according to the invention for use in the treatment of hyperpigmcntation of the skin. ageously, the cosmetic composition according to the invention is used for reducing and/or removing and/or preventing pigmentation spots on the skin.

Advantageously, the cosmetic composition according to the ion is used for bleaching and/or lightening the skin and/or bristles and/or hair.

The use of a molecule of the formula I and/or a plant extract containing such molecule according to the present invention thus makes it possible to even out the skin tone: which is characterized by a uniform, lighter, more transparent, brighter skin tone. This results in the ness ofthe skin tone being therefore ed.

Advantageously; the cosmetic composition according to the ion is used for evening out the skin tone.

The advantages obtained with the composition according to the present invention are V particularly beneficial to sensitive skins, regardless of their nature (dry, normal, oily), and more particularly for sensitive skins which are dull and lack brightness.

Advantageously, the cosmetic composition according to the invention is used in sensitive skins.

The use of the molecules of the formula (1) and/or the plant extracts ning them according to the present ion is advantageous for: — either reducing and/or removing spots of pigmentation, such as spots of hyperpigmentation due to proinflammatory , for example UV—induced brownish pigment spots, or reducing and/or removing ma; - reducing and/or inhibiting the production of melanins, which are responsible for pigmentation.

The cosmetic and/or dermatological compositions according to the invention may include, besides the active ingredient(s), a physiologically acceptable medium; i.e. which is compatible with the skin and/or the scalp, the mucous membranes, the hair, the es and/or the eyes.

Preferably, the cosmetic or dermatological composition according to the t invention comprises an amount of the molecule of the formula (I), as an active ingredient, of between 10 mg and 5 g, and more preferably n 100 mg and 1 g per 100 g of said composition.

Preferably, the cosmetic or dermatological composition according to the present invention comprises an amount of the plant extract of the invention, as an active ingredient, of between 0.1 g and 10 g, and more preferably between 1 g and 5 g per 100 g of said composition.

The cosmetic and/or dermatological composition ing to the present invention may advantageously be ed in any dosage forms y used in the ic and dermatological fields for topical or oral use.

Preferably, the topical form may be particularly provided in the form of: — an optionally gelled aqueous or hydroalcoholic solution, — an optionally ase lotion-type dispersion, — an oil-in—water or in-oil or multiple emulsion, — an aqueous gel, and may be provided as a serum, a cream, a gel, an ointment, a milk, a lotion, a paste or a foam. It may also be applied as an aerosol or as a solid, including for example in the form of a stick.

One of the advantages of the present invention is that the compositions according to the invention show a good skin tolerance, even on sensitive skins, regardless of their nature (dry, normal, oil y)_ 1000414472 This ition may also be provided in an oral dosage form, such as a tablet, a capsule, a powder for drinkable sions.

The composition may also comprise any components usually used for the intended application. Those include water, solvents, mineral, animal and/or vegetable oils, waxes, pigments, chemical or mineral filters, antioxidants, fillers, surfactants, izers, preservatives, aromas, and coloring agents.

The composition may also e a depigrnenting active ingredient according to the invention with other depigmenting actives well known to those skilled in the art, including: vitamin C derivatives, resorcinol derivatives more particularly 4-n-butylresorcinol or 4-(1- phenylethy1)benzene-l,3-diol, hydroquinone, arbutin, kojic acid and derivatives thereof, tocopherol derivatives.

The choice and/or the amount of the one or more ingredients will be also ined by the c needs of the skin and/or bristles and/or hair to which the composition will be applied, as well as by the properties and consistency that are d for the composition ing to the present invention.

Another aspect of the invention relates to a ic method for ing and/or lightening the skin and/or bristles and/or hair comprising the application to the skin and/or bristles and/or hair of a cosmetic composition according to the invention.

Another aspect of the invention relates to a cosmetic method for reducing and/or removing and/or preventing pigmentation spots on the skin comprising the application on the skin of a cosmetic composition as defined in the invention.

Another aspect of the invention relates to a molecule of the following formula (VI) Hot-NJ 0 OH if 2"}, ‘x g OH It is preferably obtained by chemical or biochemical synthesis, or from a plant extract.

Reference to any prior art in the specification is not, and should not be taken as, an acknowledgment, or any form of suggestion, that this prior art forms part of the common general knowledge in Australia or any other jurisdiction or that this prior art could reasonably be expected to be ained, understood and regarded as relevant by a person skilled in the art. 1000414472 10a10a As used , except where the context requires ise, the term "comprise" and variations of the term, such as ”comprising H H , comprises” and "comprised", are not intended to exclude other additives, components, integers or steps.

The invention will be better understood with reference to the following non—limiting examples which are specific embodiments of the cosmetic and/or dermatological compositions according to the invention.

Example 1: Preparation of an t of aerial parts of IIelic/ziysum gymlmcephalum kg of dried aerial parts were extracted twice with 35 and 25 L of 95% ethanol under reflux. The combined filtrates were concentrated and dried. The extract obtained, in the form of a brown paste, contained 0.28 g of gymnochalcone per 100 g of solids.

Example 2: Preparation of Linderatin by chemical synthesis The linderatin was obtained by a ep synthesis ing the reaction scheme below, disclosed in literaturexv,xvi O CH refxv UVCN D 0I HO OH HO OH (VII) The synthesis of molecule (VII) was performed by condensation of phloroglucinol —trihydroxybenzene) with hydrocinnamonitrile in the presence of ZnClz and HCl gas in anhydrous ether.

O OH O m ref xvi + HO OH O HO OH O (VII) andrene linderatine (Ill) atin was then obtained by condensation of oc—phellandrene which is commercially available from Sigma Aldrich (95%) and the molecule (VII) in the presence of para—toluene sulfonic acid in anhydrous benzene.

The resulting linderatin was identical in all respects to the natural product disclosed in literature”. 2012/050669 Example 3: Preparation of gymnochalcone from the aerial parts of uysum gymnocephalum : The aerial parts were dried and ground, before being extracted with ethyl acetate. Such extract was fractionated on a medium pressure silica column eluted with heptane, dichloromethane and acetone, resulting in l 1 fractions after TLC analysis and combination of identical fractions. Active fraction 8 was then fractionated on C—18 grafted silica with a gradient of acetonitrile/water + 0.1% acetic acid, resulting in ion of gymnochalcone of the formula VI (0.02% yield/dry .

Structural data: Analysis by electrospray source mass spectrometry in positive ion mode gave the adduct [M+Na]+ = 431.3 and [2M+Na]4r = 839.4. In negative ion mode, [M—H]' = 407.3 was found. The mass of the compound was therefore 408 g/mol. In MS/MS a 152 fragment was released ponding to a-terpineol (or p—menth~1-enol).

Mono- and bi-dimensional proton and carbon NMR is resulted in the identification of the structure in relative configuration, having the empirical fonnula CQSHZXOS- gymnochalcone (VI) The NMR profile was characteristic of 2’,4’,6"trihydroxychalcone (11), except in the 3’ position. It was also very close to that of linderachalcone UV)“, with the exception of the 8”, 9” and 10” positions, which were further deshielded due to the presence of a yl function at 8”, WO 98134 Functional "Position group Table 1: NMR shifts (in ppm) of the proton and carbon atoms of gymnochalcone in deuterated chlorofonn.

Example 4: Preparation of methyl—linderatin from leaves of Piper atluncum The leaves were dried and ground, before being extracted with ethanol 96 (1wt/10vol) by maceration at room temperature for 15 hrs, in the dark. This extract (17% yield) was fractionated on a medium pressure silica column eluted with heptane, ethyl acetate and methanol, resulting in 21 fractions after TLC analysis and ation of identical fractions.

Fractions 3 and 4 were subsequently fractionated by semi-preparative HPLC on C-18 grafted silica with a nt of acetonitrile/water, resulting in isolation of methyllinderatin of the formula V (13% yield/extract, 2.2%/dry plant).

The NMR and mass ometry data were consistent with those disclosed in literature for methyllinderatin“.

Examples of cosmetic compositions Examgle 1: Depigmenting’ serum Compound Amounts atin 0.1g (Di)Sodium EDTA 0,05t00.5g Cetearyl alcohol/Ceteareth 33 lto 10g Caprylyl (Di)Ether 1t010g Glyceryl stearate lt08 g (Cyclopenta)decamethyl Siloxane ltolO g Capric capryliC/trigly. 3O 7O lto 10 g Glycolic acid 1t05 g Sodium hydroxide 1to3 g Benzoic acid qs Purified water tolOOg Examgle 2: Bleaching! Cream Compound Amounts Dry extract 'chrysum gymnocephalum 0.5g Carbomer K 0.2 t02g Purified Chlorphenesine 0.05 tolg yethanol qs Cetyl l g Sorbitan palmitate lt08g (Poly) Sorbate 40 0.1 t02g Capric capryliC/trigly. 3O 7O lto 10g (p)Ethylhexyl methoxycinnamate ltolOg (alpha) Tocopheryl acetate 0.5g (Tri)Ethanolamine 0.8g 3O MBBT/Decylglucoside Mix lto 10g Purified water to 100g Pharmacological testing: inhibition of melanin synthesis: cytes are star-shaped cells, which are contained in minor proportion in the basal layer of the epidermis. Their main function is to insure melanogenesis, a process whereby melanin is synthetized to specialized organelles, known as melanosomes, then transported and buted to the neighboring keratinocytes via their dendritic extensions.

This contact with keratinocytes enables skin pigmentation, a protection mechanism of the epidermis against the nic effects of ultraviolet rays. Each melanocyte is related with about thirty-six keratinocytes, thus forming an «epidermal—melanin unit».

Melanogenesis consists of a series of enzymatic and spontaneous reactions, having ne as a precursor. Three major enzymes take part in this process: tyrosinase, and tyrosinase—related proteins 1 and 2 (TRP l and 2)“.

Some exogenous molecules are known to down—regulate melanogenesis. uinone inhibits melanin synthesis by providing a substrate for nase in order to divert its activityx'll Arbutin which contains hydroquinone acts in the same way. Kojic acid decreases the activity of tyrosinase by inhibiting UV-induced hyperpigmentationxm. Vitamin C inhibits tyrosinase but also behaves like a powerful reducer by preventing oxidative coloration of n. Vitamin A decreases the expression of tyrosinase and TRP-ZXW, We have developed a test for measuring melanin synthesis by using a metric assay on the murine melanoma cell line B16-F10. This assay enables to test the depigmenting power of active ingredients.

H "NW. nmw “ “6331551515 " .............

ICStl 1 mochalcone' 17uM Linderatin Arbutin Hydmi‘éiiiérWW W “ EtOHQSeXtIact t)l;fifihi’hifllfllfll gyl’lli’lUCé’p/lélllllil l i it ' H H T L N , l ,,,,,,,,,,,,,,,_ ”NM“... WWW ,._c,_,,c_._,_,,, Bioorganic & Medicinal try 13, 2005, 433—441 Orjala 1. er al. New monotei‘pene-substituted dihydrochalcones from Piper aa’urzczmz. Helv.

Chem. Acla 1993, 76, 1481—1488 Portet B. et al., Activity~guided isolation of antiplasmodial dihydrochalcones and flavanones from Piper hostmannz‘anum var. berbicense. Plzytochemistry 2007, 68, 1312—1320 Ichino K. et (11., Revised structures of Linderatone and methyllinderatone. Heteroeycles 1990, 31, 549—553.

V Ichino K. e! (11., Studies on the flavonoid components ot‘Lindera umbellala THUNB. Var. membranacea ) MOMIYAMA Chem Pharm Bull 1989 37, 944—947 lchino K. ez £21., A new ne, neolinderatone, from Lz’ndera umbellata THUNB. Var.

Lancea MOMIYAMA. Chem Pharm Bull 1989,37, 1426-1427 Vii lchino Ker al., Two novel flavonoids from the leaves of : umbellata var. Lancea and L. ata. Tetrahedron 1988, 44, 3251—3260 Vi“ Shimomura H. et al., A chalcone derivative from the bark of Lindera umbellczta.

Phytoclzemistry 1988, 27, 3937—3939 Ichino K., Two flavonoids from two Lindera umbellata varieties. Phytochemz‘stry 1989, 28, 955-956 K Benosman A. et (11., New terpenylated dihydrochalcone derivatives isolated from Mitrella kentz'i. J. Nat. Prod.1997, 60, 4.

XiJimbow,K. er al. Intracellular lar trafficking of tyrosinase gene family protein in eu- and pheomelanosome biogenesis. Pigment Cell Res. 2000. ,‘13 Suppl 8. 3110. ~7. 13 Suppl 8, 110-117.

Curto,E.V. er al. Inhibitors of mammalian melanocyte tyrosinase: in vitro comparisons of alkyl esters of gentisic acid with other putative inhibitors. Biochem. Pharmacol. 1999, 57, 663-672.

Kuwabara,Y. et al. Topical ation of gamma-Tocopherol tive Prevents UV- lnduced Skin Pigmentation. Biol. Pharm. Bull. 2006. Jun. ,'29. (6. )31175. —9. 29, 11754 179 Ortonne, J. P. and Bissett, D. L. (2008) JInveStig.DermatolSymp.Proa2008/1pr;l3(1):10— 4. 13, 10-14 XV Kamarul, A. M et al. Tetrahedron 59 (2003), 61 13 m Crombie L, et al. J. Chem. Soc, Perkin Trans. 1988, 1251 1001186405 THE

Claims (2)

CLAIMS 1. DEFINING THE INVENTION ARE AS S:

1. An extract of Helichrysum gymnocephalum (DC) Humbert enriched with one or more molecules of the following formula (I): 5 wherein is a single bond or a double bond; Rl = H or CH3; and R2 = H or OH, wherein said extract comprises one or more molecules of the formula (I) in an amount of 10 between 0.1 and 30 g per 100 g of dried material, and wherein said extract is obtained from a solid/liquid extraction in an organic solvent ed from esters, alcohols, ketones, nated hydrocarbons or a mixture thereof.

2. A process for preparing an extract according to claim 1 comprising the 15 following series of steps:  harvesting, drying and grinding aerial parts of Helichrysum gymnocephalum (DC) Humbert (Asteraceae, syn. Stenocline gymnocephala),  extracting the ground al obtained from the previous step with an organic solvent at a plant/solvent ratio of n about