MXPA99008250A

MXPA99008250A - Composition against the ageing and its use

Info

Publication number: MXPA99008250A
Application number: MXPA/A/1999/008250A
Authority: MX
Inventors: Castelli Dominique; Ries Gerd
Original assignee: Roc
Priority date: 1998-09-04
Filing date: 1999-09-06
Publication date: 2000-10-01

Abstract

The present invention relates to a composition intended to combat the effects of ageing of the skin and/or the exoskeleton, to the use of such a composition and to a method for the cosmetic treatment of changes associated with ageing of the skin and/or the exoskeleton. In particular, the present invention relates to a cosmetic composition, characterized in that it contains a combination of at least one retinoid chosen from retinol, esters thereof and retinaldehydes, with at least one plant hormone chosen from the group consisting of phyto-sterols and ethoxylated derivatives thereof, pentacyclic triterpenes, isoflavones, isoflavone glucosides, coumestanes and saponosides, and at least one cosmetically acceptable excipient. This composition is particularly intended to improve the elasticity of the skin and/or is intended for the prevention or treatment of changes in the skin and the exoskeleton associated with ageing.

Description

COMPOSITION AGAINST THE AGING OF THE SKIN AND / OR THE EXOQUISETTE AND ITS USE DESCRIPTIVE MEMORY The present invention relates to a composition designed to combat the effects of aging of the skin and / or the exoskeleton, the use of said composition and the method for the cosmetic treatment of changes associated with skin aging and / or skin aging. exoskeleton The skin consists of three compartments, the epidermis, the outer layer in which the stratum corneum is located, the dermis and, deeper, the hypodermis. There are exchanges between these various dermal and epidermal compartments, whose intention is to ensure the renewal of the cells and the cohesion and wetting of the outer layers. The dermis comes from the biosynthetic activity of fibroblasts, which develop the constituents of the extracellular matrix. This matrix is formed by four main families of macromolecules: collagens, elastin, structural glycoproteins and proteoglycans. It is known that aging is a physiological phenomenon that follows a period of growth. It is reflected in particular by the thinning of the skin and a loss of elasticity, which leads to the appearance of more or less deep wrinkles; In addition, a dry surface is present and an unusual pigmentation can also be observed.

It is particularly known that the aging process involves an increase in the content of a specific class of enzymes, which are called matrix metalloproteinases, in particular the collagenases of MMP-1 and the stromelysins of MMP-3, as well as a reduction in the content of the tissue compounds, which inhibit the activity of metalloproteinases; referred to hereinbelow as "ITMP inhibitors" (corresponding to "tissue metalloproteinase inhibitor"). These phenomena associated with aging are reflected in the gradual destruction of the extracellular matrix and therefore, in particular, in the appearance of the visible signs of skin aging. The article by C. Mauch et al., "Role of the Extracellular Matrix in the Degradation of Connective Tissue", Arch. Dermatol. Res (1994), 287: 107-114, can be read in that respect, in particular as regards the ITMP inhibitors. Many active agents have been proposed to prevent or retard the effects of aging. It has been shown in particular that retinoids have a favorable effect to improve the appearance and condition of the skin and combat the signs of aging. Now it has been found, totally surprising and unexpected, that the use of a combination of certain retinoids with a specific class of plant hormones makes it possible to enhance the activity of the retinoid used, or even more, to provide a synergistic effect, to visibly counteract the associated effects with the aging of the skin and / or the exoskeleton. Very particularly, the use of said combination makes it possible to enhance the activity of the retinoid, or even more to provide a synergistic effect to increase the content of inhibitors of ITMP-1 and therefore, counteract the destruction of the extracellular matrix, associated with aging. , as explained above. This result is the most surprising, since the use of such a combination does not cause a significant effect in the increase of metalloproteinases, which one skilled in the art could, however, have expected, in the context of a phenomenon of feedback regulation in response to increasing the content of ITMP inhibitors. This result is even more surprising, since the use of such a combination does not cause a significant reduction in cell growth (or proliferation). In fact, those skilled in the art could have also expected that a reduction in metalloproteinase activity, induced by increasing the content of ITMP inhibitors, would lead to a reduction in cell movement., therefore, resulting in contact inhibition of cell division and consequently, an undesirable reduction in cell turnover. In other words, the retinoid-plant hormone combination, according to the invention, makes it possible with great advantage to counteract the aging process associated with metalloproteinase activity without, however, undesirably favoring any other aging process associated with a reduction in cell turnover. Therefore, the present invention relates to a cosmetic composition, characterized in that it contains a combination of at least one retinoid selected from retinol, esters thereof and retinaldehydes, with at least one plant hormone selected from the group consisting of phytosterols and ethoxylated derivatives of it, pentacyclic triterpenes, Soflavones, isoflavone glycosides, cumestans and saponosides, and at least one cosmetically acceptable excipient. As regards the retinoid, which can be used in the composition according to the invention, retinol and its esters are very particularly preferred. The term "retino!" it should be understood as including hydrogenated and non-hydrogenated isomers, such as 9-cis-retinol and didehydroretinol. The retinol esters which can be used as retinoids in the composition according to the invention are, in particular, the esters obtained with acetic acid, propionic acid, palmitic acid or stearic acid. Furthermore, the term "retinaldehydes" should be understood as including the four trans, 13-cis, 11-cis and 9-cis stereoisomeric forms.

As regards the plant hormone which can be used in the composition according to the invention, the phytosterols and the ethoxylated derivatives thereof are very particularly preferred. Among these, mention may be made in particular of β-sitosterol, α-sitosterol, β-sitosterol, β-sitostanol, stigmaterol, stigma-ethanol, campesterol or campestanol. For example, ei-sitosterol can be used in the form of the product referred to as "Ultra" (mainly consisting of β-sitosterol) as sold by the company Kaukas. In the case of the use of a mixture of phytosterols, mention may be made, for example, of the product referred to as "Primal" (mainly consisting of β-sitosterol, α-sitosterol and campesterol) as sold by the company Kaukas. The term "ethoxylated derivatives" of phytosterols refers, according to the invention, to phytosterols, in particular those mentioned above, in which the hydroxyl group has been replaced with a group of the formula H (OCH2CH2) nO- (I ) where n represents an integer between 1 and 100 and preferably between 5 and 50. Mention may be made, for example, of the products referred to as "E5", "E10", "E15", "E25" and "E50" which sells the company Kaukas, which are ethoxylated β-sitosterols, figures 5,10, 15, 25 and 50 indicate the value of n in the group of formula (I). Among the pentacyclic triterpenes that can be used in the composition according to the invention, mention can be made in particular of the oleanans (with β-amyrin), friedellans (with friedelin), taraxastanes (with taraxasterol) or ursanos (with a-amyrin). Among the soflavones which can be used in the composition according to the invention, mention should be made in particular of daidzein or genistein. Among the isoflavone glycosides which can be used in the composition according to the invention, mention may be made in particular of daidzin or genistin. Among the cumestans that may be used in the composition according to the invention, mention may be made in particular of the cumesterol. Finally, among the saponosides that can be used in the composition according to the invention, mention should be made in particular of the licorice glycyrrhizin (Glycyrrhizz glabra), Centella asiatica saponosides, mimosa saponosides (Mimosa tenuiflora), cempasuchil saponosides (Calendula officinalis) or primrose saponosides (Primula veris). According to a particularly preferred embodiment of the invention, the retinoid is retinol and the plant hormone is β-sitosterol or an ethyloxylated derivative thereof. Preferably, the composition according to the invention has a retinoid concentration between 0.0001 and 3% by weight and a plant hormone concentration between 0.0001 and 5% by weight, relative to the total weight of the composition.

The composition according to the invention also consists of at least one cosmetically acceptable excipient, adapted for external local administration. The excipients adapted to the formulation are known to those skilled in the art and consist of, in particular, thickeners, emulsifiers., preservatives agents, dyes, fragrances, etc. The composition according to the invention can be prepared according to the operating conditions that are part of the general knowledge of those skilled in the art. The composition according to the invention can therefore be, for example, in the form of a solution, a gel, a lotion, a cream, an oil-in-water emulsion or a water-in-oil emulsion, or it can be combined with any cosmetically acceptable vector, such as liposomes. Finally, the composition according to the invention can, needless to say, also contain cosmetic ingredients such as humectants, softeners or chemical or organic filter agents. Because of the activity of the retinoid / plant hormone combination, in particular of the combination of retinol with β-sitosterol, in the contents of the inhibitors and ITMP and of the metalloproteinases, the composition according to the invention has an advantageous effect on the main signs of aging, in terms of efficacy, in relation to a composition containing only the retinoid of this combination.

Therefore, it has been observed that the retinoid / plant hormone combination makes it possible at least to enhance the activity of the retinoid and still, in certain cases, to obtain synergism. The first effects can be observed after a few weeks of use of the composition, which are exerted towards the inner layers. These effects constitute a reduction in the number and / or depth of wrinkles, softening the surface of the skin and its irregularities, reaffirming the skin and moisturizing it. The composition according to the invention also makes it possible to unify the color and appearance of the face and / or prevent or reduce the appearance of age marks, stretch marks and cellulite. The composition according to the invention is particularly suitable for combating wrinkles and loosening of tissues. It also protects the skin against the aggression of the environment, in particular against the aggression of UV rays and pollution. Provides a unified appearance and prepares the skin for the application of other cosmetic products and makeup. The composition according to the invention can be used either in the morning and / or at night, on the face or on the hands or on any other part of the body. In the epidermis of the hands, it will be particularly suitable to reduce hyperpigmentation and to combat the appearance of age marks, as well as to increase the firmness of the tissues in this region, which have a tendency to become flabby with age.

The composition according to the invention is particularly suitable for treating the areas surrounding the eyes and lips, which are very fragile and which are highly susceptible to the appearance of wrinkles and loosening of the tissue. And it is particularly well tolerated in this sensitive region, in which, due to the preferably synergistic activity of the retinoid / plant hormone combination, its anti-aging activity will be exerted after a few weeks of application. This composition visibly makes it possible to reduce the number of wrinkles and bags under the eyes; It firms the particularly sensitive skin around the eyes, mouth and neck. Finally, the composition according to the invention can also be applied to the exoskeleton, in particular to hair and nails. It makes it possible mainly to strengthen the nails, since it prevents them from becoming brittle, and improving their appearance in particular by combating the appearance of lines and / or marks. The present invention also relates to the use of a combination of, at least one retinoid, selected from retinol, esters thereof, and retinaldehydes, with, at least one plant hormone selected from the group consisting of phytosterols and ethoxylated derivatives thereof, triterpenes pentacyclics, soflavones, soflavone glycosides, cumestans and saponosides, for the preparation of a composition for the purpose of increasing the content of tissue metalloproteinase inhibiting compounds.

In particular, this use is such that the prepared composition is a cosmetic composition or a pharmaceutical composition. When the prepared composition is a pharmaceutical composition, it is preferably a dermatological composition. Very particularly, this use is characterized in that the composition prepared has the purpose of improving the elasticity of the skin and / or whose purpose is the prevention or treatment of changes in the skin and the exoskeleton, associated with aging. In particular, the use is characterized in that the retinoid is selected from retinol and its esters. Moreover, the use is characterized in that the plant hormone is selected from phytosterols and ethoxylated derivatives thereof, and is preferably selected from the group consisting of β-sitosterol, α-sitosterol, β-sitosterol, β-sitostanol, stigmaterol, stigma-ethanol , campesterol and campestanol and ethoxylated derivatives thereof. In addition, as described above for the composition, the use is characterized in that the retinoid is present at a concentration between 0.0001 and 3% by weight and because the plant hormone is present at a concentration between 0.0001 and 5% by weight, in relation to the total weight of the composition. Still very particularly, the use is characterized in that the retinoid is retinol and the plant hormone is β-sitosterol or an ethoxylated derivative thereof.

In particular, the use described above makes possible the preparation of a dermo-cosmetic composition for the purpose of improving the viscoelastic properties of the skin and preventing or reducing the formation of wrinkles. By "dermo-cosmetic composition" is meant, of course, a cosmetic composition or a dermatological composition. In addition, the present invention also relates to a method of cosmetic treatment, for increasing the content of metalloproteinase inhibiting compounds of the tissue, characterized in that the composition, constituted by the combination of at least one retinoid with at least one plant hormone, as described above, it is applied to the skin and / or the exoskeleton. Finally, the present invention also relates to a method for the cosmetic treatment of the changes associated with the aging of the skin and / or the exoskeleton, characterized in that the composition, constituted by the combination of at least one retinoid with at least one A plant hormone, as described above, is applied to the skin and / or the exoskeleton. The present invention will now be illustrated with the help of examples, which, under no circumstances should be interpreted as possibly limiting its scope.

EXAMPLE 1 Study of the anti-aging activity of the combination of retinol with β-sitosterol in vitro in the fibroblasts of the dermis of a human 1) Equipment and method Fibroblasts were isolated from the human dermis from a biopsy taken from the plastic surgery operation in a 65-year-old patient. They were used in the thirteenth passage and approximately 80,000 cells were inoculated into 24-well culture plates with 0.5 ml of culture medium supplemented with 10% fetal calf serum and antibiotics. After 48 hours of inoculation, the cells were treated with the test product at varying concentrations of the latter, in a culture medium containing 1% fetal calf serum. Each concentration was tested three times. After incubation for two days at 37 ° C (eg in "D2" below), the number of cells in half of the cultures was measured. The cells of the other half of the cultures were again treated, in D2, with the test product to carry out a measurement of the number of cells after incubation for 5 days at 37 ° C (eg in "D5" Mentioned below). Measurements of the number of cells, in particular for the study of cell proliferation, were carried out with a "Coulter counter", the cell counter sold by the Coultronics company.

The following measurements of ITMP-1, MMP-1 and MMP-3 were carried out with ELISA equipment in the supernatant of the cell culture medium, recovered and stored at -80 ° C before being measured. For each series of measurements, the control was untreated cultures or supernatants from untreated cultures. 2) Study of the change in 1TMP-1 During aging in vivo, the content of ITMP-1 is reduced as explained above. The activity of a composition according to the invention, in this content of ITMP-1 was measured in D2 and D5.

The results are given in table 1 below (the results in said table are expressed in nanograms of ITMP-1 per cell). Therefore, it can be observed that the combination of the retinoid / plant hormone of a composition according to the invention, makes it possible at least to significantly enhance the activity of the retinoid, if not to provide a synergistic effect, with respect to the increase in the content of the ITMP-1 inhibitors. 3) Study of the change in MMP-1 and MMP-3 During in vivo aging, the content of metalloproteinases MMP-1 (collagenase) and MMP-3 (stromelysins) increases as explained above, which leads to a gradual destruction of the extracellular matrix. The activity of a composition according to the invention in this content of MMP-1 or MMP-3 respectively, was measured in D2 and D5. The results are given in Tables 2 and 3 below, respectively (the results are expressed in nanograms of MMP-1 or MMP-3 per cell). Therefore, it can be seen that the retinoid / plant hormone combination of a composition according to the invention makes it possible to reduce the content of metalloproteinases MMP-1 and MMP-3. In particular, it should be noted that the increase in the content of ITMP-1 inhibitors does not result in any significant increase, because of a phenomenon of feedback regulation of the metalloproteinase content. 4) Study of cell proliferation The activity of a composition according to the invention, in cell proliferation was measured in D2 and in D5. The results (expressed as the number of cells) are given in Table 4 below. Therefore, it can be seen that the retinoid / plant hormone combination of a composition according to the invention does not result in any significant undesirable reduction in cell turnover.

EXAMPLE 2 Anti-aging composition in the form of an oil / water emulsion % - Glycerol 5,000 - Disodium EDTA 0.200 - Methyl 4-hydroxybenzoate 0.200 - propyl 4-hydroxybenzoate 0.070 - 2-phenoxyethanol 0.730 - Water q.s.

- Polyacrylamide and isoparaffin of C13-14 and laureth-7, as marketed by SEPPIC under the name of "Sepigel 305". 2,000 - Dimethicone 2,000 - Cetearyl alcohol 0.500 - Ciclometicone 1,500 - Isopropyl Palmitate 2.000 - BHT 0.100 - trialkyl citrate of (C14-C15) 4.000 - 90 ° alcohol 6.000 - Hydrogenated polyisobutene 4.000 - Butylene glycol 2,000 Stearic acid 1,000 Sodium hydroxide 0.100 Retinol 0.300 - ß-sitoesterol 0.500 Total 100% EXAMPLE 3 Anti-aging composition in the form of an oil / water emulsion % - Water q.s.

- "Carbopol 980" carbomer, such as the 0.300 sold by GOODRICH - Glicerol 5,000 - PEG-8 2,000 - EDTA Disodium 0.200 - Sodium Hydroxide 0.135 Glyceryl stearate / PEG-100 stearate such as that marketed by ICI under the name of "Alarcel 165" 5,000 - Cetearyl octanetoate / isopropyl myristate such as that marketed by STEARINERIE DUBOIS under the name "Dub liquide" 3,000 - Glyceryl stearate 3.000 - Stearic alcohol 0.500 - Cetostearyl alcohol 0.500 - Cetyl Palmitate 0.500 - Talc 0.200 - BHT 0.100 - Methyl 4-hydroxybenzoate 0.160 - propyl 4-hydroxybenzoate 0.056 - 2-phenoxyethanol 0.584 - C12-15 alkyl benzoate 4.000 - Dimethicone 1,000 - Retinol 0.092 - ß-sitoesteroi 0.150 Total 100% EXAMPLE 4 Composition according to the invention in gel form % Glycerol 5,000 disodium EDTA 0.200 methyl 4-hydroxybenzoate 0.200 propyl 4-hydroxybenzoate 0.070-2-phenoxyethanol 0.730 - Water q.s.

- Polyacrylamide and isoparaffin of C13-14 and laureth-7 2,000 - Dimethicone 2,000 - Cetearyl alcohol 0.500 - Ciclometicone 1,500 - Soapyl Palmitate 2.000 - BHT 0.100 - trialkyl citrate of (C14-C15) 4.000 - Alcohol 90 ° 6,000 - Hydrogenated polyisobutene 4.000 - Butylene glycol 2,000 - Retinol 0.300 - ß-sitoesterol 0.500 Total 100% EXAMPLE 5 Composition according to the invention in the form of a lotion (water / oil emulsion) % - Cyclomethicone 25,000 - 2-polyglyceryl sesquisaterate / beeswax / 12,000 mineral oil / magnesium stearate / aluminum stearate, such as that marketed by HOECHST under the name "Hostacerin WO" - Phenyl dimethicone 6,000 - Dimethicone 3.000 - Isopropyl myristate 3,500 - BHT 0.050 - Water q.s.p.

- C12-15 alkyl benzoate 3.000 - Methyl 4-hydroxybenzoate 0.160 - propyl 4-hydroxybenzoate 0.056 - 2-phenoxyethanol 0.584 - ß-sitosterol 0.500 - Disodium EDTA 0.100 - Retinol 0.040 Total 100% TABLE 1 Ni O TABLE 2 NEITHER TABLE 3 NJ tO TABLE 4 Not U

Claims

NOVELTY OF THE INVENTION CLAIMS

1. - A cosmetic composition characterized in that it contains a combination of at least one retinoid selected from retinol, esters thereof and retinaldehydes, with at least one plant hormone selected from the group consisting of phytosterols and ethoxylated derivatives thereof, pentacyclic triterpenes, isoflavones, glycosides of isoflavone, cumestans and saponosides, and at least one cosmetically acceptable excipient.

2. The cosmetic composition according to claim 1, further characterized in that the retinoid is selected from retinol and its esters.

3. The cosmetic composition according to claim 1 or 2, further characterized in that the plant hormone is selected from phytosterols and ethoxylated derivatives thereof.

4. The cosmetic composition according to any of the preceding claims, further characterized in that the plant hormone is selected from the group consisting of β-sitosterol, α-sitosterol, β-sitosterol, β-sitostanol, stigmasterol, stigmastanol, campesterol and campestanol, and ethoxylated derivatives thereof.

5. The composition according to any of the preceding claims, further characterized in that the retinoid is retinol and the plant hormone is β-sitosterol or an ethoxylated derivative thereof.

6. The composition according to any of the preceding claims, further characterized in that the retinoid is present at a concentration between 0.0001 and 3% by weight, and because the plant hormone is present at a concentration between 0.0001 and 5% by weight, in relation to the total weight of the composition.

7. The use of a combination of at least one retinoid selected from retinol, esters thereof and retinaldehydes, with at least one plant hormone selected from the group consisting of phytosterols and ethoxylated derivatives thereof, pentacyclic triterpenes, isoflavones , isoflavone glycosides, cumestans and saponosides, for the preparation of a cosmetic composition for the purpose of increasing the content of metalloproteinase tissue inhibiting compounds.

8. The use according to claim 7, further characterized in that the purpose of the cosmetic composition is to improve the elasticity of the skin and / or whose intention is also to prevent or treat changes in the skin and in the exoskeleton, associated with the aging.

9. The use according to claim 7 or 8, further characterized in that the retinoid is selected from retinol and its esters.

10. - The use according to any of claims 7 to 9, further characterized in that the plant hormone is selected from phytosterols and ethoxylated derivatives thereof.

11. The use according to any of claims 7 to 10, further characterized in that the hormone vegeta! it is selected from the group consisting of β-sitosterol, a-sitosterol, β-sitosterol, β-sitostanol, stigmaterol, stigma-ethanol, campesterol and campestanol, and ethoxylated derivatives thereof.

12. The use according to any of claims 7 to 11, further characterized in that the retinoid is retinol and the plant hormone is β-sitosterol or an ethoxylated derivative thereof.

13. The use according to any of claims 7 to 12, further characterized in that the retinoid is present at a concentration between 0.0001 and 3% by weight, and that the plant hormone is present at a concentration between 0.0001 and 5% by weight, in relation to the total weight of the composition.

14. The use according to any of claims 7 to 13, for the preparation of a cosmetic composition for the purpose of improving the viscoelastic properties of the skin and preventing or reducing the formation of wrinkles.

15. The method of cosmetic treatment, for increasing the content of metalloproteinase inhibitor compounds of the tissue further characterized in that a composition is constituted by the combination as defined in any of claims 7 and 9 to 13 and is applied to the skin and / or to the exoskeleton. 16.- The method for the cosmetic treatment of changes associated with the aging of the skin and / or the exoskeleton, further characterized in that a composition constituted by the combination as defined in any of claims 7 and 9 to 13, is applied to the skin and / or the exoskeleton. 17. The use of the combination as defined in any of claims 7 and 9 to 13, for the preparation of a pharmaceutical composition for the purpose of increasing the content of tissue metalloproteinase inhibiting compounds. 18. The use according to claim 17, further characterized in that the pharmaceutical composition is a dermatological composition. 19. The use according to claim 17 or 18, further characterized in that the composition prepared has the purpose of improving the elasticity of the skin and / or whose intention is the prevention or treatment of changes in the skin and the exoskeleton. , associated with aging. 20. The use according to any of claims 17 to 19, for the preparation of a dermatological composition for the purpose of improving the viscoelastic properties of the skin and preventing or reducing the formation of wrinkles.