MX2007004110A - Extracts of curcuma longa and their cosmetic and dermatological uses. - Google Patents

Abstract

The present invention refers to an extract obtained from the aerial parts of Curcuma longa, a cosmetic or dermopharmaceutical composition containing said extract, as well as the use of such extract or composition for regulating or inhibiting the androgen-dependant mechanisms at a skin or scalp level..

Description

EXTRACT OF LONGA CURCUMA AND ITS COSMETIC OR DERMOFARMACEUTICAL APPLICATIONS BACKGROUND OF THE INVENTION The present invention relates to an extract obtained from the aerial parts of Curcuma longa, a cosmetic or dermopharmaceutical composition containing such an extract, as well as to the use of such extract or such composition to regulate or inhibit the androgen-dependent mechanisms to level of the skin or scalp.

Today, many people are affected, to varying degrees, by one or several disorders called androgen-dependent, having as their common origin an alteration of the metabolism of the androgen hormone testosterone (P. Vexiau, "Hormones et peau", Cosmétologie (1996 ), No. 10, pp. 43-47). These alterations can be of genetic or pathological origin, but they can also be linked to the aging process. At the level of the skin or the scalp, the most common of these hormonal disorders are the growth of unwanted hairs at the level of the body or on the face, mainly hirsutism in women, acne, hyperseborrhea or alopecia.

Another finding is that today, in Western societies, men, almost as much as women, want to reduce their hairiness. In both sexes, a glabrous skin has become a symbol of beauty. To respond to this aspiration and Growing need, new hair removal techniques have been developed. However, they are often stressful and expensive. An alternative is today to apply dermatological compositions on the skin that can interfere locally with the metabolism of testosterone, the main regulator of hair growth.

In a general way, there is an effective demand in terms of providing products or preparations that allow acting on the androgen-dependent mechanisms, both at the level of the skin and the scalp.

Thus, in order to satisfy this need, the plaintiff discovered, curiously, unexpectedly, and is the basis of the present invention, that the extracts of the leaves or flowers of Curcuma longa, had a remarkable reduction or inhibition activity in the metabolization of testosterone, thus procuring a new response for the treatment of androgen-dependent disorders, for aesthetic and dermatological needs.

Among the formulations present in the market for which an "anti-androgenic" general action is affirmed, useful for the aforementioned applications, it should be noted in the state of the art, the presence of numerous preparations or associations of plant origin. Thus, by way of example, we can cite the ethanolic extract of the plants "Maj ihto" and / or "Kachur" recommended to fight against alopecia, seborrhea and acne (patent JP2002 / 241297). A cosmetic or dermatological composition based on extract of myrrh (Commiphora myrrha) is intended to regulate the sebum secretion of the skins to grease or acne tendencies, as well as to treat acne, hirsutism, as well as to diminish the growth of hairs of the face (patent WO00 / 04872) -. Another composition for topical application, based in particular on an extract of cedar wood and cinnamon, is found in an application for the control of seborrhea and in the treatment of acne (patent US2004 / 228822). An action of inhibition of androgenic receptors is attributed to substances extracted from Japanese plants, whose interest would be exercised especially against acne and male alopecia (patents JP2000 / 001432 and JP8193094). For certain of these preparations characterized by a plant presence, reference is sometimes made, clearly, as in the international patent application WO02 / 19974, of an inhibitory effect of the enzyme 5-alpha reductase, enzyme of interest since responsible for the conversion of testosterone into another androgen more powerful and particularly active in the sebaceous glands of the skin and the hair follicle, dihydroxytestosterone.

The herbaceous plant Cúrcuma longa, of the botanical family of the Zingibéraceas, was also cited. To the reading of the monograph of this plant (Alternative Medicine Review (2001), vol.6, pp. S62-S66) and of the following examples of preparations given to the public knowledge, it is verified that it is a rhizome, that is to say an underground trunk, which constitutes the part of the plant used classically for medical purposes and mainly for the treatment of androgen-dependent disorders. The rhizome, once boiled, washed and dried, gives a yellow powder (or "turmeric" in English) rich in phenolic compounds called curcuminoids ("Le turmeric", Nutranews, Juin 2002), such as curcumin, tetrahydrocurcumin, Dimethoxyurcumin, etc. This yellow powder is attributed to antioxidant, hepatoprotective, anti-inflammatory, anticarcinogenic and antimicrobial properties, which also make the Curcuma longa interest in traditional and Ayurvedic medicines ("La médecine ayurvédique", Nutranews, Septembre 2003). Thus, by way of examples involving the turmeric rhizome as such, or indirectly, the latter when curcumin or an analog thereof is highlighted, and this is pointed out in the patent applications or patents JP3176414, WO03 / 088927, JP9255568 and US2003 / 105030. The first document mentions that acne and alopecia are the targets of a cosmetic agent based on Japanese and Chinese plants, mainly based on turmeric rhizome. The following three disclose the use of curcumin or its analogues to oppose various androgen-dependent disorders.

Despite all this information, it should be noted that a reducing or inhibiting effect on the metabolism of testosterone for the extracts of Curcuma longa has never been indicated or even suggested. of the aerial parts of the plant, nor has it been described the use of this same type of extract, or compositions based on these, to combat the growth of unwanted hairs on the face or body, for the prevention or the fight against acne, hyperseborrhea and male seborrhoeic alopecia.

With the expressions "aerial parts", previously mentioned, the flowers and leaves of the plant should be indicated. The leaves and flowers of Curcuma longa were certain the object of research, the majority however almost systematically concerns the essential oils obtained by hydrodistillation. The literature reveals, for these volatile leaf or flower oils, a large proportion in monoterpene derivatives, particularly in terpinolenes (Chane-Ming J. et al., J. Essent, Oil Res. (2002), vol. 249-251). It is particularly disclosed, for an essential oil based on turmeric leaves, an anti-inflammatory activity (Lyengar MA et al., Indian Drugs (1994), vol.31, pp.528-531) so an insecticidal action against the coleoptera (Tripathi AK et al., J. Econ. Entomol. (2002), vol.95, pp.183-189).

Detailed description of the invention According to a first purpose, the invention has for its object an extract of Curcuma longa, characterized in that: It is obtained from the aerial parts of the plant, harvested parts at a special time of the year to guarantee maximum contents in active compounds, preferably in the autumn (March and April) when they are harvested at a latitude close to the tropical Capricorn, Presents a reduction or inhibition activity on the metabolism of testosterone. The extract of Curcuma longa can be advantageously isolated from the aerial parts of the plant, dehydrated and crushed. Detailed description of the invention The extract of Curcuma longa can be advantageously isolated from the aerial parts of the plant, dehydrated and crushed.

One of the other characteristics of said extract is that it mainly contains derivatives of the phenylpropanoid type and derivatives of the flavonoid type, substances that are also used as "tracer" allowing to "standardize" the extract. However it is very important to emphasize the absence total of curcumin and of apparent compounds in the aerial parts of the plant. The properties shown by an extract obtained from these aerial parts are therefore not attributable to the presence of such substances, contrary to the rhizome Curcuma longa.

This extract, which constitutes a new product, contains derivatives of the phenylpropanoid and flavonoid type, in a mass content between 0.05 and 3%.

Said extract can be obtained following a simple procedure and technique. First, the aerial parts of the Curcuma longa are harvested, dehydrated and grossly crushed. Then an extraction is made with alcoholic solvents, hydroalcoholic or such other polar solvent (DMF, DMSO, acetonitrile, etc.), under stirring and at reflux. Once the extraction is done, and after the exhaustion of the vegetable, the organic solvents are eliminated, then the volume of the extract is adjusted with water. It is also possible to add a miscible glycol in water to guarantee the solubility of certain constituents of the extract.

According to an advantageous variant, in an extract titrated at 0.1% by weight of flavonoid derivatives, the extract contains from 0.01 to 0.5% by weight of derivatives of the phenylpropanoid type, in particular from 0.01 to 0.1%. .

According to an advantageous embodiment of the invention for obtaining a more active and more stable extract, a controlled acid hydrolysis reaction is carried out in the extract in solution, particularly allowing the production of flavonoid-type aglycone derivatives. The enhanced activity of this extract can be explained in part by the formation of compounds that penetrate more easily into the epidermis, such as the aglycone flavonoids.

The flavonoid-type aglycone derivatives that have been identified in the extract and used as trace elements to standardize the extract are quercetin and camferol, while the identified phenylpropanoid-type derivatives are ferulic acid and coumaric acid. .

According to a second purpose, the present invention also comprises a cosmetic or dermopharmaceutical composition including, as a reducing agent or inhibitor of the metabolism of testosterone, an effective amount of the extract as previously defined. This is incorporated in the composition with all cosmetically or pharmaceutically acceptable excipients. Such a composition is substantially free of extract from the curcuma of Curcuma longa.

Advantageously, the content of extract in the composition described above is comprised between 1 and 10% by weight with respect to the total weight of such composition, preferably between 1 and 5% by weight.

The said composition is also capable of including another active element chosen from agents for which an inhibitory effect on the activity of specific enzymes is known, by which we know that they are involved in the metabolism of testosterone at the level of the skin or scalp. These enzymes may be protein kinase C, ornithine decarboxylase, adenylosuccinate synthetase, aspartate transcarbamylase, gamma-glutamyl transpeptidase, S-adenosylmethionine decarboxylase, NO-synthetase (or NO-synthase), serine protease, and -alfa-reductase. According to a preferred embodiment of the present invention, an agent capable of inhibiting the activity of the enzyme ornithine decarboxylase, such as eflornithine hydrochloride, or that of the enzyme NO synthase, such as NG-nitro, is selected. -L-arginine methyl ester.

According to a more particular mode of the invention, pointing out an aesthetic benefit associated with a limitation of hair growth, said composition may optionally also include urea (up to a concentration of 20%) and NG-nitro L-arginine methyl ester.

The cosmetic or dermopharmaceutical compositions are formulated to be applied topically on the skin in the form, by example, milk, gel, cream, lotion, emulsion, etc ... They can also be administered orally (administration per os) in the form of tablets, capsules, ampoules, syrup, drops, etc ...

By way of illustration, some examples of formulations of cosmetic or dermopharmaceutical composition according to the invention are mentioned below, containing the aforementioned Curcuma longa extract: Formula A (topical application: anti-growth-hair) Turmeric extract (turmeric extract) 5% Hydrogenated polydecene (hydrogenated polydecene) 5% Caprilic / Capric Triglycerides (capric / caprylic triglycerides) 2% Ethoxydiglycol oléate (ethoxydiglycol oleate) 8% Glyceryl stearate (glyceryl stearate) 3% Dimethicone (dimethicone ) 1% PEG-100 stearate (and) glyceryl stearate (polyethylene glycol-100 stearate and glyceryl stearate) 5% Glycerin (glycerin) 3% Carbomer (acrylate / acrylamide copolymer &mineral oil) 0.2% Sodium hydroxide (sodium hydroxide) 0.4% Chlorphenesin (chlorphenesin) 0.2% Phenonip (parabens (butyl parahydroxybenzoate, ethyl, isobutyl, methyl, propyl and phenoxyethanol) 0.6% Wheat germ oil (wheat germ oil) 1 , 5% Sesamus indicum oil (sesame oil) 1.5% PEG-8 &Tocopherol &Ascorbyl Palmitate &Ascorbic acid &Citric acid (polyethylene glycol-8 &tocopherol &ascorbyl palmitate &ascorbic acid &citric acid) 0, 07% Urea (urea) 5% Efflornithine chlorhydrate (eflornithine hydrochloride) 1% NG-nitro-L-arginine methyl ester (methyl ester of NG-nitro-L-arginine) 1% Aqua (water) qsp 100% Formula B (topical application: male seborrhoeic alopecia) Turmeric extract (turmeric extract) 3% Glyceryl stearate & stearyl alcohol (glyceryl stearate &stearyl alcohol) 5% Stearyl alcohol (stearyl alcohol) 2% Hydrogenated polydecene (hydrogenated polydecene) 8% Cáprilic / Capric Triglyceride (caprylic / capric triglycerides) 5% Cetearyl isononanoate (cetearyl isononane) 2% Dicaprylyl carbonate (dicapryl carbonate) tmurarol% Wax alba (beeswax) 1% Propylparaben (propyl paraben) 0.3% Aqua (water) 10% Ethylenediamine-tetraacetic acid disodium salt dihydrate (EDTA) (Disodium salt of ethylene diamine tetraacetic acid dihydrate) 0.2% Glycerin (glycerin) 3% antha gum (xanthan gum) 0.4% Emulzome Macadamia (hydrogenated polyisobutene &stearyl heptanoate &macadamia oil &methyl paraben) 5% Triethanolamine (triethanolamine) 0.35% Aqua (water) qsp 100% Formula C (topical acne application) Turmeric extract (turmeric extract) 2% Hydrogenated polydecene (hydrogenated polyisobutene) 8% Caprilic / Capric Triglyceride (capric triglycerides / caprí1 s) 2% Ethoxydiglycol Oléate (ethoxydiglycol oleate) 8% Glyceryl stearate (stearate of glyceryl) 2% Dimethicone (dimethicone) 1% PEG-100 stearate (and) glyceryl stearate (polyethylene glycol-100 stearate and glyceryl stearate) 5% Propylparaben (propyl paraben) 0, .3% Stearyl alcohol (stearyl alcohol) 1% Aqua (water) 10% Ethylenediamine-tetraacetic acid disodium salt dihydrate (EDTA) (disodium salt of ethylene diamine tetraacetic acid dihydrate) 0.2% Glycerin (glycerin) 2% Xantha gum (xanthan gum) 0.4% wheat germ oil (wheat germ oil) 1% Macadamia Ternifolia seed oil (Macadamia seed oil) 1% PEG-8 & Tocopherol & Ascorbil Palmitate & Ascorbic acid & Citric acid (polyethylene glycol-8 &tocopherol Ascorbile palmitate &ascorbic acid &citric acid) 0.07% Triethanolamine (triethanolamine) 0.35% Aqua (water) qsp 100% Formula D (anti-hair growth application: per os administration) Turmeric extract (turmeric extract) 4% Excipients qsp 1 capsule in gelatin: soy lecithin, soybean oil, fatty acid glycerides According to a third purpose, the present invention relates to the use of the Curcuma longa extract as previously defined as a cosmetic agent intended to reduce or inhibit the metabolism of testosterone, in particular it seeks to decrease the growth of undesirable hairs on the face or the body, or to fight against or prevent hyperseborrhea and male alopecia. Particularly, it is sought with said extract, to decrease the growth of undesirable hairs on the face and body.

Another purpose of the present invention relates to the use of the Curcuma longa extract as previously defined for the manufacture of a dermopharmaceutical composition intended to reduce or inhibit the metabolism of testosterone, and particularly to combat or prevent acne and the hirsutism. It also concerns the use of an extract of Curcuma longa as previously defined for the manufacture of a cosmetic composition intended to decrease or inhibit the metabolism of testosterone, in particular to reduce the growth of undesirable hairs on the face or body, or to fight against or prevent hyperseborrhea and androgen-dependent alopecia.

Preferably, it is sought, with this latter composition, to decrease the growth of unwanted hairs of the face or body.

Finally, the invention is illustrated, purely and simply by way of indication, of a part by the attached in vitro test (test 1).

Test 1: Evidence of the effect of a Curcuma longa extract on the metabolism of testosterone in reconstructed epidermis of human origin (provider: SkinEthic®).

These epidermis constitute a biological material that has a strong homogeneity with the human epidermis, and allow to realistically test a product dedicated to be applied on the surface of the skin. A glycolic extract of Curcuma longa leaves was then tested at different concentrations. Its action was, on the other hand, compared to that of a specific inhibitor of 5-alpha-reductase, Finasteride® (reference molecule in this type of evaluation).

Reconstructed epidermis of 17 days were thus pre-cultivated in 24-well plates, for 24 hours. Then 100 Di of marked testosterone They were deposited on the stratum corneum of each epidermis. After 24 new hours, the culture media was collected for analysis. You check the metabolization of testosterone by silica thin layer chromatography and by direct counting of the radioactivity of the different spots, with the help of a "Optiquant version 3 (packard)" program. Different metabolites, and especially dihydrotestosterone (DHT), were identified with the help of standards. Each point is the average of 3 measurements made on different epidermis.

The results are found in the following table: The glycolic extract indicates strong añti-androgen activity revealed by a dose-dependent inhibition of the metabolism of testosterone (the% inhibition is expressed with respect to the reference without treatment). The comparison with the Finastéride, a specific inhibitor of the enzyme 5-alpha reductase, shows that the extract inhibits this enzyme, but also acts on other enzymes involved in the metabolization of testosterone (effect revealed by chromatography).

On the other hand, always by way of indication, the invention is also illustrated by three attached in vivo tests (tests 2 to 4).

Test 2: Evidence of the effect, topically, of a cosmetic composition mentioned above on the growth of unwanted hairs.

A statistical study was conducted in a panel of 25 men and women from 20 to 50 years old, with an important growth of the hair under the armpits. A raffle was made to know the subjects "with treatment" or "without" treatment. Among the subjects with treatment, we had women and men who should apply, after shaving of the armpits, daily, morning and evening, for 20 days, either formula A under the form of lotion, or a lotion "placebo" (without active substance). The results are found in the attached table: After only 20 days of treatment, it is observed, compared to the subjects without any treatment, that 80% of the subjects "with treatment", who applied the formula A, object of the present invention, have seen the length of their hair under the armpits reduced by at least 39%.

Test 3: Evidence of the effect, topically, of an extract of Curcuma longa against male seborrhoeic alopecia.

In the framework of a preliminary study, a glycolic extract of leaves of Curcuma longa, titrated at 0.25% in active ingredients was tested on eight men under 40 years of age presenting early signs of androgenetic alopecia. It should be noted that the activity of an extract / formulation, for the purpose of combating hair loss, can be evaluated, in first intention, by following the ratio of the number of hairs in the anagen phase to the number of hairs in the telogen phase. Thus, a ratio of less than 4 denotes a suspicious disturbance that can be classified as pathological if it becomes less than 3 (P. Bouhanna, "Garder et retrouver ses cheveux", Ed. Springer-Verlag, 2000, and references cited).

This study of clinical pre-evaluation was then carried out for 3 months in these eight volunteers, at a rate of two daily applications, in the morning and at night. The following results should be noted (confirming the anti-gallop potential of this active and very positive results in a developed formulation): 5 (five) cases have seen their initial ratio "hair in anagen phase on hairs in telogen phase" significantly increased and become clearly superior to 5, with the observation of a coating partial visible of some depopulated areas of the scalp. Only one case, did not present an improvement. It should be noted that two cases were not classified as "positive", despite an increased ratio and a visible improvement in the quality of hair growth.

Test 4: Evidence of the effect of a previously mentioned composition, administered orally, on the growth of undesirable hairs.

Among the women who attend a beauty institute, 12 women volunteers were selected, with regular visits (once a month) at this Institute to make a waxing in the legs. In the framework of the present test, these women have accepted to orally absorb in the form of a capsule, an oily extract of Curcuma longa (formula D above) at a dose of one capsule daily fasting for a month. At the end of this month, we have done a survey with these 12 (twelve) women, and you can notice for each a delay on the date of "necessary" hair removal in the said Institute, justifying a significant anti-growth effect of the hairs Thus, it was observed: that, for 5 (five) of them, the delay was around one week that, for 4 (four) of them, the delay was 2 (two) weeks. that, for the remaining 3 (three), the delay was such that they could avoid a monthly session.

Claims (18)

1. Extract of Curcuma longa obtained from the aerial parts of the plant, characterized in that it presents a reduction or inhibition activity on the metabolization of testosterone and in that it contains derivatives of the phenylpropanoid type and flavonoid type derivatives.

2. Extract according to claim 1, characterized in what is obtained from the aerial parts of the plant, dehydrated and crushed.

3. Extract according to any of claims 1 and 2, characterized in that it contains derivatives of the type phenylpropanoids and flavonoids, with a mass content comprised between 0.05 and 3%.

4. Extract according to any one of claims 1 to 3, characterized in that it contains, in an extract titrated to 0.1% by weight of flavonoid derivatives, from 0.01 to 0.5% by weight of derivatives of the phenylpropanoid type.

5. Extract according to claim 4, characterized in that it contains 0.01 to 0.1% by weight of derivatives of the phenylpropanoid type.

6. Extract according to any one of claims 1 to 5, characterized in that the phenylpropanoid-type aglycone derivatives are chosen in the group consisting of ferulic acid and coumaric acid and in which the flavonoid-type derivatives are chosen in the group constituted for campferol and quercetin.

7. Cosmetic or dermopharmaceutical composition, characterized in that it includes, as a reducing agent or inhibitor of the metabolism of testosterone, an effective amount of the Curcuma longa extract according to any of claims 1 to 6, and a cosmetically or pharmaceutically acceptable excipient .

8. Composition according to claim 7, characterized in that the content of extract is comprised between 1 and 10% by weight with respect to the total weight of the composition.

9. Composition according to claim 8, characterized in that the content of extract is comprised between 1 and 5% by weight with respect to the total weight of the composition.

10. Composition according to any one of claims 7 to 9, characterized in that it includes, in addition, another active element chosen among the inhibitors of protein kinase C enzymes, ornithine decarboxylase, adenylosuccinate synthetase, transcarbamylase aspartate, gamma-glutamyl transpeptidase, the S-adenosylmethionine decarboxylase, NO-synthetase, serine protease, and 5-alpha-reductase.

11. Composition according to any of claims 7 to 10, characterized in what optionally includes urea and NG-nitro-L-arginine methyl ester.

12. Composition according to any of claims 7 to 11, characterized in that it is formulated to be applied topically on the skin in the form of milk, gel, cream, lotion, emulsion.

13. Composition according to any of claims 7 to 11, characterized in that it is formulated to be administered orally in the form of tablets, capsules, ampoules, syrup, drops, etc ...

14. Use of a Curcuma longa extract according to any of claims 1 to 6 as a cosmetic agent to reduce or inhibit the metabolism of testosterone, and more particularly to decrease the growth of unwanted hairs of the face or body, or to fight against or prevent hyperseborrhea and male alopecia.

15. Use according to claim 14, in which the extract is used to decrease the growth of unwanted hairs of the face and body.

16. Use of a curcuma longa extract according to any of claims 1 to 6 for the production of a dermopharmaceutical composition intended to reduce or inhibit the metabolism of testosterone, and particularly to combat or prevent acne and hirsutism.

17. Use of a Curcuma longa extract according to any of claims 1 to 6 for the production of a cosmetic composition intended to reduce or inhibit the metabolism of testosterone, and more particularly to decrease the growth of unwanted hairs of the face or of the body, or to fight against or prevent hyperseborrhea and androgen-dependent alopecia.

18. Use according to claim 17, wherein the composition is used to decrease the growth of unwanted hairs of the face or body.