FR2784027A1 - USE OF A BOLDO EXTRACT IN A COSMETIC OR DERMATOLOGICAL PRODUCT AND PRODUCT COMPRISING SUCH AN EXTRACT - Google Patents

Abstract

The invention relates to the use of a boldo extract in a cosmetic or dermatological product and to a product that contains said extract. The invention specifically relates to the use of a boldo extract as an active ingredient on its own or added to at least one other active ingredient for the preparation of a cosmetic or dermatological product for preventative or curative treatment of ageing symptoms in tissue by local or external application on skin, nails and/or hair.

Description

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DESCRIPTION
The present invention relates to the field of cosmetic and dermatological products or preparations, especially those effective for the treatment of tissue aging, and relates to the use of a Boldo extract for the treatment of tissue aging and a cosmetic product or dermatological composition comprising such an extract.

 The Boldo (Peumus boldus Mol.) Is a small, bushy tree belonging to the Monimiaceae family and growing spontaneously on the sunny hills of Chile. Boldo is used as a medicinal plant in traditional medicine.

 Thus, in the Andes, Boldo leaves are used as an infusion against liver diseases and intestinal intoxications, poultices on the temples against headaches and migraines, baths against rheumatism and decoction as emetic. Boldo leaves are used as diuretic, stomachic and sedative.

 In addition, the leaves are used as anthelmintic and the juice extracted leaves is used, instillation in the ear, to treat otitis.

 According to the literature, Boldo leaves contain 1.2% tannins, 2-3% essential oils (including 45% ascaridol and 30% cineole and a mixture of many terpenes), flavonoids or flavonic glycosides (have been isolated: pneumoside, boldoside, fragoside ...) and 0.25-0.50% of aporphinic alkaloids with boldine as the main alkaloid (25% of the total alkaloid content).

 It has recently been reported that boldine has a choleretic and cholagogue effect (DE-2,547,243) and a relaxant effect on smooth muscle (Speisky and Cassels, Pharmacological Research, Vol 29, No. 1, 1-12). , 1994).

 In addition, boldine has also been reported to have antioxidant activity, free radical neutralization effect and peroxidation inhibition effect (cytochrome P-450 system, microsomal membranes).

 In addition, a hepatoprotective and anti-inflammatory effect of the hydroalcoholic extracts of Boldo leaves has been reported (Bruneton, "Pharmacognosy, Phytochemistry, Medicinal Plants", 2nd Ed., Lavoisier, Paris, 1993,737-739 / Wichtl, "Teedrogen und Phytopharmaka ", 3. Aufl., Wissenschaftliche Verlagsgesellschaft, 1997, 110-112) and boldine has been proposed in the treatment

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 drug and drug-induced hepatotoxicity in autoimmune and inflammatory diseases (Speisky and Cassels, 1994 - mentioned above).

 Finally, US-5,348,755 discloses the use of boldine as an antioxidant in edible oils, and US-4,185,119 and US-5,594,033, respectively, report antiallergic and anti-arrhythmic activity for boldine.

 However, despite these multiple pharmaceutical and therapeutic applications, no targeted application in the field of cosmetics or dermatology has been mentioned to date.

 However, the authors of the present invention have found, unexpectedly and surprisingly, that Boldo extracts, in particular consisting of aporphinic alkaloids and more particularly boldine, had, in addition to the activities indicated above, many other properties and effects. remarkable, making these extracts particularly effective in combating various phenomena and reactions involved in tissue aging, especially those caused or accelerated by solar radiation.

 Thus, the main object of the present invention is the use of a Boldo extract as an active agent, alone or in combination with at least one other active agent, for the preparation of a cosmetic or dermatological product for the preventive or curative treatment of the aging of the tissues, for external topical use for the skin, the nails and / or the hair.

 According to a preferred embodiment of the invention, the Boldo extract used consists of boldine or an enriched boldine extract, in particular extracted from Boldo leaves.

 The remarkable properties and effects of Boldo extracts, especially boldine, have been identified through various tests described in more detail below.

1) EFFECTS ON THE GROWTH OF HUMAN FIBROBLASTS IN IN VITRO CULTURE
1) Operating mode
Human fibroblasts were inoculated in a defined culture medium (DMEM). After incubation for 24 hours at 37 ° C. in a 5% CO 2 atmosphere, the boldine (for example - not limiting - the Boldine marketed by SIGMA, reference B3916, lot 94H10481) was added at two different concentrations.

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 After incubation for 3 days at 37 ° C. and in a 5% CO 2 atmosphere, the growth of fibroblasts was evaluated by counting the cells using a particle counter and by enzymatic determination of ATP.

 Fetal calf serum (FCS), which contains many growth factors (IGF, PDGF, etc.) and nutrients (glucose, proteins, amino acids, etc.), has been used as a positive standard in these tests. tests on human fibroblasts (in growth and survival) in vitro.

2) Results obtained with boldine (in% compared to the control)

<Tb>
<tb> Concentration <SEP> of <SEP> boldine <SEP> Number <SEP> of <SEP> fibroblasts <SEP> Rate <SEP> of ATP
<tb> (% <SEP> p / v) <SEP> (*) <SEP> (*)
<tb> 0 <SEP>% <SEP> = <SEP> control <SEP> 100 <SEP> 100
<tb> 0.001 <SEP>% <SEP> 105 <SEP> 116
<tb> 0.003 <SEP>% <SEP> 110 <SEP> 124
<Tb>
(*) Average of 3 tests in triplicate
3) Results obtained with fetal calf serum (FCS) (in% relative to the control)

<Tb>
<tb> Concentration <SEP> of <SEP> SVF <SEP> Number <SEP> of <SEP> fibroblasts <SEP> Rate <SEP> of ATP
<tb> (% v / v) <SEP> (*)
<tb> 0 <SEP>% <SEP> = <SEP> control <SEP> 100 <SEP> 100
<tb> 0.1 <SEP>% <SEP> 112 <SEP> 125
<tb> 0.3 <SEP>% <SEP> 135 <SEP> 155
<Tb>
(*) Average of 3 tests in triplicate
Examination of these tables shows that boldine clearly stimulated the growth and metabolism of human fibroblasts in vitro. Although tested at doses 100 times lower than those of FCS, boldine showed an effect comparable to SVF although of more moderate intensity.

II) EFFECT OF IMPROVING SURVIVAL ON HUMAN FIBROBLASTS IN VITRO
The improvement in survival was evaluated on a saturated fibroblast culture. At saturation, the proliferation of fibroblasts undergoes a so-called "contact" inhibition. The test makes it possible to quantify on the quiescent cells a certain number of parameters: - general metabolic activity by measuring the level of ATP, - protein synthesis,

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 - synthesis of glutathione.

I) Operating mode
The fibroblasts were seeded in the defined culture medium (DMEM). Boldine was added in the crop 72 hours after sowing. The parameters cited were evaluated after incubation for 72 hours at 37 ° C. in a 5% CO 2 atmosphere.

 ATP was assayed by a chemiluminescent enzymatic system (Kemp, 1986), proteins were assayed by the Bradford colorimetric reaction (Bradford, 1986) and reduced glutathione (GSH) was measured by a fluorescent probe, the orthophthalaldehyde (Hissin and Hilf, 1976).

 NB: the GSH level is expressed per mg of protein then in% / untreated control.

2) Results obtained with boldine (in% compared to the control)

<Tb>
<tb><SEP> Concentration of <SEP><SEP> ATP <SEP><SEP> Rate of <SEP> Proteins <SEP><SEP>SEP> GSH Rate
<tb> boldine <SEP> (% <SEP> p / v) <SEP> (*) <SEP> (*) <SEP> (*)
<tb> 0 <SEP>% <SEP> = <SEP> control <SEP> 100 <SEP> 100 <SEP> 100
<tb> 0.002 <SEP>% <SEP> 131 <SEP> 157 <SEP> 96
<tb> 0.005 <SEP>% <SEP> 166 <SEP> 201 <SEP> 100
<Tb>
(*) Average of 2 tests in triplicate
3) Results obtained with fetal calf serum (FCS) (in% relative to the control)

<Tb>
<tb><SEP> Concentration of <SEP><SEP> ATP <SEP><SEP> Rate of <SEP> Proteins <SEP><SEP>SEP> GSH Rate
<tb> SVF <SEP> (% <SEP> v / v) <SEP> (*) <SEP> (*) <SEP> (*)
<tb> Witness <SEP> 100 <SEP> 100 <SEP> 100
<tb> 0.1 <SEP>% <SEP> 123 <SEP> 108 <SEP> 105
<tb> 0.3 <SEP>% <SEQ> 140 <SEQ> 117 <SEP> 120
<Tb>
(*) Average of 3 tests in triplicate
Boldine has stimulated the synthesis of ATP, proteins and GSH.

For ATP and GSH, and although tested at doses 50 times lower than those of FCS, boldine showed effects comparable to those of FCS. In addition, for proteins, the stimulation of boldine was greater than that observed for FCS.

 The results of the paragraphs 1 and II show the interest of the use of the boldine in Cosmetology of care (skincare, hair care, care

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 nails) and its predictable effectiveness in topical cosmetic preparations intended to combat cutaneous and capillary aging or in the treatment of tired skin, hair, dander requiring stimulation of their metabolisms and their protein synthesis.

III) ACTIVITY "ANTI-PROTEASES"
Proteases secreted by polymorphonuclear neutrophils (PMN) during inflammation or by fibroblasts irradiated by UV-A, cause degradation of proteins that structure the extracellular matrix of the dermis.

1) Tubal anti-collagenase assay (Van Wart et al., Anal Biochem., 113, 356-365, 1981)
Polymorphonuclear leukocytes (PMN) during inflammation and "aged" or irradiated fibroblasts secrete collagenases. The tests were performed with Clostridium histolyticum collagenase and a chromogenic synthetic substrate: FALGPA. The incubation is 30 minutes at room temperature and the optical density is measured at 324 nm. The comparatively tested standard inhibitor is cysteine.

<Tb>
<Tb>

Concentrations <SEP> in <SEP>% <SEP> (w / v) <SEP> Results <SEP> in <SEP>% <SEP> inhibition
<tb> Witness <SEP> 0
<tb> Boldine <SEP> to <SEP> 0.03 <SEP>% <SEP> 1
<tb> Boldine <SEP> to <SEP> 0.1 <SEP>% <SEP> 40
<tb> Boldine <SEP> to <SEP> 0.3 <SEP>% <SEP> 100
<tb>CI,; () <SEP> in <SEP>% <SEP> p / v <SEP> 0.12 <SEP>% <SEP>
<tb> Concentrations <SEP> of <SEP> cysteine <SEP> (in <SEP>% <SEP> p / v <SEP> Results <SEP> in <SEP>% <SEP> inhibition <SEP> (p / v)
<tb> 0 <SEP> 0
<tb> 1.8 <SEP> 44
<tb> 2.6 <SEP> 63
<tb> 3.5 <SEP> 77
<tb> CI $ 0 <SEP> in <SEP>% <SEP> p / v <SEP> 2.0 <SEP>%
<Tb>

These results illustrate another advantageous property of boldine, in favor of the use of boldine in cosmetology to fight skin aging and / or superficial body growths, photoinduced or intrinsic.

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IV) "ANTI-SUBSTANCE P" ACTIVITY
1) Inhibition of substance P "ex vivo" (Ebertz et al., Journal of Investigative Dermatology, 88 (6), 682-685, 1987)
Substance P is a neuropeptide released by certain sensory nerve fibers from the skin after irritation. This peptide acts on specific receptors present on skin cells (fibroblasts, keratinocytes, Langerhans cells) to induce either proliferation (fibroblasts and keratinocytes) or immunomodulation (Langerhans cells). On mast cells, substance P induces the release of histamine responsible for the erythema observed in vivo. It is this phenomenon which has been evaluated on skin biopsies incubated at 37 ° C. in the presence of substance P. The histamine released is assayed by an ELISA technique.

<Tb>
<Tb>

Concentrations <SEP> in <SEP>% <SEP> (w / v) <SEP> Histamine <SEP><SEP> released <SEP>% <SEP> / control
<tb> in <SEP> micromole <SEP> by <SEP> liter <SEP> by
<tb> biopsy
<tb> Witness <SEP> 0.8 <SEP> 0
<tb> Control <SEP> + <SEP> Substance <SEP> P <SEP> 1,4 <SEP> 100
<tb> Substance <SEP> P <SEP> + <SEP> Boldine <SEP> to <SEP> 0.01 <SEP>% <SEP> 1.3 <SEP> 81
<tb> Substance <SEP> P <SEP> + <SEP> Boldine <SEP> to <SEP> 0.1 <SEP>% <SEP> 1.2 <SEP> 69
<Tb>

These results clearly indicate the advantage of a topical use of boldine in cosmetology to soothe sensitive skin irritated by chemical substances (pollution) or by physical stresses (UV, heat, drought) or psychosomatic.

V) ACTIVITY "ANTI-GLYCATION"
1) Inhibition of "in tubo" glycation (Deyl et al., Mechanisms of Aging & Development, 55 (1), 39-47, 1990 / Monnier et al., Proceedings of the National Academy of Sciences of the USA, 81 (1), 583-587, 1984)
The non-enzymatic glycation of proteins is a decisive process in the aging of human tissues and explains the crosslinking of extracellular matrices and basement membranes, which is responsible for most of the pathologies observed in diabetics. In addition, Schiff's bases catalyze the production of reactive forms of oxygen, which exacerbate the effects of non-enzymatic glycation. In tubo tests were performed on type 1 collagen incubated for 21 days at 45 ° C. in the presence of 1% glucose. The base rate of

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Schiff was assessed by fluorimetry at 430 nm (excitation at 350 nm). The collagen fixed glucose level was evaluated by thiobarbituric acid (densitometry at 443 nm).

<Tb>
<Tb>

Concentrations <SEP> in <SEP>% <SEP> Results <SEP> in <SEP>% <SEP> by <SEP> report <SEP> in <SEP> control
<tb> (w / v) <SEP> Fluorescence <SEP> -I --- <SEP> Fixed Glucose <SEP>
<tb> 0 <SEP>% <SEP> = <SEP> control <SEP> 100 <SEP> 100
<tb> Boldine <SEP> to <SEP> 0.01 <SEP>% <SEP> 78 <SEP> 77
<tb> Boldine <SEP> to <SEP> 0.1 <SEP>% <SEP> 48 <SEP> 42
<Tb>

Aminoguanidine has also been tested as a positive standard in this tubal glycation model.

<Tb>
<Tb>

Concentrations <SEP> in <SEP> Results <SEP> in <SEP>% <SEP> by <SEP> report <SEP> in <SEP> control
<Tb>

aminoguanidine ~~~~~~~~~~~~~~~~~~~~~~~~~

aminoguanidine ~~~~~~~~~~~~~~~~~~~~~~~~~

<Tb>
<tb> (in <SEP>% <SEP> w / v) <SEP> Fluorescence <SEP> Glucose <SEP> fixed
<tb> 0 <SEP>% <SEP> = <SEP> control <SEP> 100 <SEP> 100
<tb> 0.003 <SEP>% <SEP> 98 <SEP> 101
<tb> 0.01% <SEP> 95 <SEP> 115
<tb> 0.03% <SEP> 70 <SEP> 112
<tb> 0.1 <SEP>% <SEP> 24 <SEP> 126
<Tb>

Examination of these tables shows that at 0.01%, boldine is more active than aminoguanidine on the fluorescence of Schiff bases and on the glucose level fixed on collagen.

 These results show the interest of the topical use of boldine in care cosmetology to reduce the effects of aging (intrinsic or photoinduced) on the proteins of the extracellular matrix of the skin (care of the skin and hair) .

VI) INHIBITION OF INDUCTION OF APOPTOSIS
1) Principle
Apoptosis is an active biological process used by living organisms to remove certain cells from their tissue, by autolysis with, in particular, destruction of proteins and nuclear DNA in small fragments released into the cytoplasm.

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 Apoptosis can be induced by oxidative stress (UV-R, inflammation), by deprivation in growth factors or by toxic substances (pollutants, genotoxic agents, etc ...).

 The principle of these tests was to highlight the ability of a substance to reduce the rate of apoptosis induced in a cell culture in vitro.

 The inducer of apoptosis retained for this study was the deprivation in growth factors: this mechanism would be responsible at least partly for the aging of tissues by disappearance of living cells.

2) Procedure a) Preparation of the cells
A549 human epithelial cells in saturated cell mats were used for this test.

At 0, the cells received a serum-free culture medium containing the various concentrations of test substances and were incubated for 4 days at 37 ° C. A batch of cells receiving medium with calf serum (containing growth factors ) was taken as a negative control. Then the cells were recovered by trypsinization to be stained and analyzed by flow cytometry. b) Quantification of the Number of Apoptotic Cells in Flow Cytometry (R. Olivier, Methods in Enzymol, Vol 251. Chapter 24. 270-278, 1995)
In studies on apoptosis, it is essential to evaluate not only the rate of apoptotic cells but also the rate of necrosis cells to confirm that the inhibition of apoptosis induction is not due to a passage in necrosis.

* Method 1: staining with fluorescent probes
In this method, the cells are stained simultaneously with a solution of ethidium bromide (5 micrograms / ml) and acridine orange (1.5 micrograms / ml).

 The necrotic cells are stained with ethidium bromide while the living cells are stained only by the acridine orange. In addition, living cells are separated into two populations according to the fluorescence intensity of orange acridine proportional to the amount of DNA: apoptotic cells with low fluorescence and non-apoptotic cells with strong fluorescence.

 * Method 2: by the peak "sub-G 1

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In this method a part of the cells is treated with trypan blue to stain and count under conventional microscope, the number of necrotic cells.

 The other part of the cells is permeabilized and then stained with a solution of ethidium bromide (5 micrograms / ml) and quantified in flow cytometry. In this part, the apoptotic cells appear as a peak called "sub-G1" because they have a reduced DNA level compared to non-apoptotic cells. The peak is called "sub-Gl" because it appears just before peak G in the frequency histogram of cell cycle studies. The GO / G peak corresponds to cells at rest or at the beginning of the cycle which contain only a copy of their genetic material. The G2 / M peak corresponds to cells having their genetic material in duplicate or already in the course of mitosis (separation of the two daughter cells). Peaks G0 / G1 and G2 / M are separated by a plateau comprising cells in intermediate phase S of synthesis of their second copy of genetic material (according to F. Lacombe, 1992).

3) Results
Figures 1 and 2 of the accompanying drawings show graphically the inhibition by boldine of apoptosis induced in A549 human cells by deprivation in growth factors, revealed by flow cytometry (Statistics: Mean +/- SEM over 3 trials / Student's t test / (*) = p <0.05).

The graphs in Figures 1 and 2 should be interpreted in relation to the results determined for the control batches shown in the tables below.

<Tb>
<Tb>

<SEP> rate in <SEP>% <SEP> (average <SEP> +/- <SEP> SEM <SEP> on <SEP> 3 <SEP> tests)
<tb> Staining <SEP> Witness <SEP> Reference
<tb> (without <SEP> serum <SEP> of <SEP> calf) <SEP> (serum <SEP> of <SEP> calf)
<tb> Living <SEP> Cells <SEP> 67 <SEP> +/- <SEP> 3 <SEP> 70 <SEP> +/- <SEP> 3
<tb> no <SEP> apoptotic
<tb> Method <SEP> 1 <SEP> Live <SEP> Cells <SEP> 15 <SEP> +/- <SEP> 4 <SEP> 2 <SEP> +/- <SEP> 0 <SEP>
<tb> apoptotic
<tb> Cells <SEP> 16 <SEP> +/- <SEP> 2 <SEP> 25 <SEP> +/- <SEP> 3
<tb> necrotic
<Tb>

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<Tb>
<tb> Rate <SEP> in <SEP>% <SEP> (average <SEP> +/- <SEP> SEM <SEP> on <SEP> 3 <SEP> tests)
<tb> Staining <SEP> Witness <SEP> Reference
<tb> (without <SEP> serum <SEP> of <SEP> calf) <SEP> (serum <SEP> of <SEP> calf)
<tb> Cells <SEP> 74 <SEP> +/- <SEP> 7 <SEP> 79 <SEP> +/- <SEP> 5 <SEP>
<tb> alive
<tb> Method <SEP> 2 <SEP> Live <SEP> Cells <SEP> 16 <SEP> +/- <SEP> 4 <SEP> 2 <SEP> +/- <SEP> 0 <SEP>
<tb> apoptotic
<tb> Cells <SEP> 26 +/- 7 <SEP> 21 <SEP> +/- <SEP> 5 <SEP>
<tb> necrotic
<Tb>

With method 1 (Fig. 1), deprivation of cells as growth factors increased the apoptosis rate from 2 to 15%. In boldine-treated cells, the rate of apoptosis dropped to 4% for the 5 mg / 1 dose.

 With method 2 (Fig. 2), deprivation of cells as growth factors increased the apoptosis rate from 2 to 16%. In boldine-treated cells, the rate of apoptosis dropped to 4% for the 5 mg dose.1

 These results show that boldine, like calf serum, has significant abilities to reduce the rate of apoptosis induced in a culture of human cells deprived of growth factors.

 Moreover, this effect of boldine is not due to a transfer of apoptosis to necrosis because the levels of necrotic cells change little according to the boldine dose.

 The effects and beneficial activities of the boldine or of a boldine enriched extract newly identified by the inventors and mentioned above, therefore include, in particular, a very high stimulating activity of the metabolism (in particular stimulation of the synthesis of ATP, reduced glutathione GSH and protein), anti-glycation activity of collagen and cutaneous proteins and a pronounced effect of stimulating cell growth.

 This surprising combination of advantageous effects on the mechanisms intervening concomitantly in the processes of cellular aging, underlines the interest of the use of boldine, even in small quantities, to mitigate preventively or curatively the aging of tissues, in particular tissues. skin.

 In addition, the additional activities of boldine or boldine-enriched extract, also mentioned above and newly identified or

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 verified by the inventors, namely, anti-protease activity (especially anticollagenase), anti-substance P activity and inhibition of the induction of apoptosis, give the boldine additional biological properties, including anti-stress effects, soothing , protector and repairer on the skin, especially after exposure to sunlight.

 The invention therefore also relates to the particularly advantageous use of boldine in a product that preferentially treats intrinsic or photo-induced tissue aging, especially at the level of the skin.

 Moreover, the subject of the invention is also a cosmetic or dermatological product for the treatment of tissue aging, in particular photoinduced, characterized in that it contains, as active agent, single or associated with at least one other agent active, a cosmetically or dermatologically effective amount of a Boldo extract, preferably boldine or an enriched boldine extract.

 According to one characteristic of the invention, especially taking into account the experimental results set out above, said cosmetic or dermatological product advantageously contains between 0.0001% and 10% by weight, preferably between 0.001% and 2% by weight, of boldine.

 According to a first embodiment of the invention, the boldine is present in the form of a hydropolyolic solute or in vectorized form (liposomes, nanospheres, nanocapsules, microspheres, microcapsules, micelles or the like).

 According to a second embodiment of the invention, the boldine is present in a grafted form, for example by amino acids, sugars, lipids or peptides.

 As non-limiting examples of practical embodiments of the invention, various cosmetic products or compositions comprising boldine as single active agent or associated with at least one other will be described below.

 Example 1 A cosmetic product according to the invention, in the form of a protective and stimulating hair lotion, may, for example, have a weight composition as indicated below.

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Formula: - Hydroxyethylcellulose 0.20 - Propylene glycol 2.00 - Cetostearyl alcohol (and) Ceteareth-20 5.00 - Lipodermol 1.00 - Cetrimonium chloride 1.00 - Glycol stearate 2.00 - Preservative qs - Wheat protein hydrolyzed 1,00 - Boldine 0,005 - Water qs 100,00
The process for the preparation and manufacture of the aforementioned lotion consists essentially of bringing all the fatty substances (cetostearyl alcohol (and) ceteareth-20, lipodermol and glycol stearate) to 75 ° C., to bring the mixture water and propylene glycol to 70 ° C. C, dissolving in this mixture at this temperature hydroxyethylcellulose, cetrimonium chloride, preservative, boldine and hydrolysed wheat protein, to pour the fatty phase in the aqueous phase with stirring and continue stirring until at complete cooling of the resulting lotion.

 EXAMPLE 2 A cosmetic product according to the invention, in the form of a night cream, stimulating, restorative and anti-wrinkle may, for example, have a weight composition as indicated below.

 Formula: Oily phase - Glycerol stearate (and) cetostearyl alcohol (and) cetyl palmitate (and) coconut glycerides 12.00 - PEG-20 glycerol stearate 2.00 - Ceteareth 20 1.00 - Octyldodecanol 3.00 - Oil of shea 3.00 - Dioctylcyclohexane 4.00 Aqueous phase - Glycerin 3.00

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- Vegeseryl # HGP: soy protein (soy wisteria) 5.00 - Boldine 0.20 - Elestab # 388 (preservative) 1.50 - Water qs 100.00 - Perfume qs
The process for the preparation and manufacture of the above-mentioned cream consists essentially in heating the constituents of the fatty phase to 80 ° C., heating the water + glycerin + preservative mixture to 80 ° C. and dissolving the boldine therein, pouring the phase fat in the aqueous phase with stirring turbine, let the resulting mixture cool, add to 60 C Vegeseryl # HGP, to add the perfume to 45 C and finally continue cooling to room temperature.

 Example 3 A cosmetic product according to the invention, in the form of a protective anti-irritant day cream for sensitive skin, may, for example, have a weight composition as indicated below.

Formula: Fatty phase - Glycerol stearate SE 16.00 - Ceteareth-12 1.00 - Octyldodecanol 6.00 - Isopropyl myristate 4.00 Aqueous phase - Glycerin 6.00 - Boldine 0.30 - Methylparaben 0.20 - Propylparaben 0.10 - Imidazolidinyl urea 0.30 - Water 65.80 - Perfume 0.30
The process for the preparation and manufacture of the above-mentioned cream may consist in heating the constituents of the fatty phase to 80 ° C., heating the water and glycerin to 75 ° C. and dissolving in this mixture at this temperature the methylparaben and the propylparaben, then imidazolidinyl urea, to dissolve in this mixture, just before emulsification, the boldine, to pour the fatty phase into the aqueous phase with stirring turbine, then to cool

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 progressively the mixture obtained by planetary stirring and turbine, to add to 45 C the perfume and finally to cool to room temperature.

 EXAMPLE 4 A cosmetic product according to the invention, in the form of anti-aging anti-glycation protective cream and antiproteases, may, for example, have a weight composition as indicated below.

Formula: Fatty phase - Stearic alcohol (and) Steareth-7 (and) Steareth-10 4.00 - Glyceryl stearate (and) Ceteth 20 2.00 - Avocado oil 3.00 - Stearyl alcohol 2.00 - Triglycerides Caprylics / capriques 3.00 - Hexyl laurate 2.00 - Isopropyl stearate 2.00 - Paraffin oil II, 00 - Cetyldimetone 1.00 Aqueous phase - Allantoin 0.10 - Boldine 0.30 - Butylene glycol 5, 00 - Elestab # 4112 (preservative) 0,35 - Water qs 100,00
The method for preparing and manufacturing the above-mentioned cream may consist in heating the constituents of the fatty phase at 80 ° C. with stirring, in bringing the water + butylene glycol + preservative mixture to 80 ° C. and in dissolving allantoin and boldine therein. , to pour the fatty phase into the aqueous phase with stirring turbine and finally, to gradually cool the resulting mixture with stirring to room temperature.

 EXAMPLE 5 A cosmetic product according to the invention, in the form of a facial tonic lotion, may, for example, have a weight composition as indicated below.

 Formula: - Propylene Glycol 5.00 - Hamamelis Water Virginiana 5.00

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- Boldine 0,10 - Elestab # 50J (preservative) 0,40 - Perfume qs - PEG-40- Hydrogenated castor oil qs - Distilled water qs 100,00
The process for the preparation and manufacture of the aforementioned lotion consists essentially in bringing the distilled water and the propylene glycol to 50 ° C. and in dissolving the preservative and the boldine therein, and then dissolving the perfume and the solubilizer (castor oil with stirring). ), add the witch hazel water, shake until cool and finally filter.

 Example 6 A cosmetic product according to the invention, in the form of an antiapoptose emulsion, may, for example, have a weight composition as indicated below.

Formula: Oily phase - PEG-25 PABA 5.00 - Ceteareth-6 (and) stearyl alcohol 2.00 - Ceteareth-25 2.00 - Cetyl alcohol 1.00 - Glyceryl stearate SE 6.00 - Paraffin oil 5 , 00 - Caprylic / capric triglycerides 5.00 - Dimethicone 0.20 Aqueous phase - Boldine 0.20 - Butylene glycol 5,00 - Elestab # 388 (preservative) 1,50 - Allantoin 0,15 - Perfume 0,20 - Distilled water qs 100.00
The process for producing and manufacturing the aforementioned emulsion may consist in heating the constituents of the fatty phase at 80 ° C. with stirring, bringing the water to 80 ° C. and adding thereto with stirring the butylene glycol, the preservative, the allantoin and boldine, to pour the fatty phase into the aqueous phase with turbine stirring, to gradually cool the mixture obtained, to

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 add the perfume towards 45 C and finally, to continue the agitation until complete cooling.

 Of course, the invention is not limited to the embodiments described. Modifications are possible, particularly from the point of view of the constitution of the various elements or by substitution of technical equivalents, without departing from the scope of protection of the invention.

Claims (13)

1) Use of an extract of Boldo as an active agent, alone or in combination with at least one other active agent, for the preparation of a cosmetic or dermatological product for the preventive or curative treatment of tissue aging, for use external topical for skin, nails and / or hair.  2) Use according to claim 1, characterized in that the Boldo extract consists of boldine or an enriched boldine extract.  3) Use according to any one of claims 1 and 2, characterized in that the extract has a stimulating activity of the metabolism and stimulating activity of cell growth.  4) Use according to any one of claims 1 to 3, characterized in that the extract also has an anti-glycation activity of collagen and cutaneous proteins.  5) Use according to any one of claims 1 to 4, characterized in that the extract also has an anti-collagenase activity.  6) Use according to any one of claims 1 to 5, characterized in that the extract also has an anti-apoptosis activity.  7) Use according to any one of claims 1 to 6, characterized in that the extract also has an anti-substance P activity.  8) Use according to any one of claims 1 to 7, characterized in that the cosmetic or dermatological product is a product more particularly treating intrinsic tissue aging or photo-induced.  9) Cosmetic or dermatological product for the treatment of tissue aging, in particular photoinduced, characterized in that it contains, as active agent, alone or in combination with at least one other active agent, a cosmetically or dermatologically effective amount of an extract of Boldo.  10) Cosmetic or dermatological product according to claim 9, characterized in that the Boldo extract consists of boldine or an enriched boldine extract.  11) Cosmetic or dermatological product according to any one of claims 9 and 10, characterized in that it contains between 0.0001% and 10% by weight, preferably between 0.001% and 2% by weight, of boldine. <Desc / Clms Page number 18>  12) cosmetic or dermatological product according to any one of claims 10 and 11, characterized in that the boldine is present in the form of hydropolyolic solute or vectorized form.  13) Cosmetic or dermatological product according to any one of claims 10 and 11, characterized in that the boldine is present in a grafted form, for example by amino acids, sugars, lipids or peptides.