WO2009122045A2

WO2009122045A2 - Use of olive oil extract to control skin aging

Info

Publication number: WO2009122045A2
Application number: PCT/FR2009/000291
Authority: WO
Inventors: Cyril Estanove; François PRUVOST; Jean-Claude Allart; Frédéric SALDMANN
Original assignee: Sprim; Bc Developpement Sa
Priority date: 2008-03-21
Filing date: 2009-03-19
Publication date: 2009-10-08
Also published as: FR2928837A1; FR2928837B1; EP2282732A2; WO2009122045A3

Abstract

The invention relates to the use of an olive oil extract in a cosmetic and/or dermatological composition. The olive oil extract contains oleocanthal and/or a derivative, with the general formula (A), hereinafter (A). Formula (I): wherein R is a hydrogen atom or a hydroxy group. The invention can be used in preparing a cosmetic composition and dermatological drug for controlling and regulating skin aging.

Description

USE OF AN EXTRACT ¹ OLIVE OIL FOR CONTROLLING THE SKIN AGING.

The present invention relates to a novel composition based on extracts derived from olive oil, and more particu larly to ^¬ oleocanthal and derivatives oleocanthal, and its use in cosmetics and dermatology for the control of skin aging and its effects.

The skin is an essential organ of life, which fulfills several functions whose quality has a decisive influence on the health of every individual. In particular, the skin is a real barrier to the environment, the effectiveness of which determines the maintenance of a good homeostatic balance. This cutaneous barrier is subjected to incessant aggressions, and the quality of its defenses is thus a major element for the effectiveness of its protection. The skin constitutes a living anatomical barrier between the body and its environment, and it comprises several integrated layers, namely a superficial layer constituted by the epidermis, and deeper layers forming the dermis and hypodermis, and each of these layers has specific properties allowing the whole to react and adapt to the conditions of its environment.

The human epidermis is particularly well adapted to play its essential function of "barrier", it limits the entry of external agents and participates in the general homeostasis of the body by regulating the loss of transepidermal water.

The epidermis is mainly composed of keratinocytes

(85 to 90% of the epidermal cells), melanocytes (2 to 3% of the epidermal cells) and Langerhans cells. Its thickness is variable according to the different parts of the body.

The dermis is thicker, and consists mainly of collagen, elastin and proteoglycans. These three types of molecules are synthesized by dermal fibroblasts. Collagen fibers provide the strength and texture of the skin, elastin is responsible for elasticity, and proteoglycans play a major role in the structure and hydration of the skin. Other cells such as macrophages and leucocytes are also present in the dermis layer. The hypodermis is the deepest layer of skin, and contains lipid-producing fat cells so that the subcutaneous tissue can make a fat layer that protects muscles, bones, and internal organs from shock.

The stratum corneum of the epidermis has a structure composed of corneocytes, flattened cells, which have neither nucleus nor cytoplasmic organelles. These cells are therefore biologically dead but still remain active. They result from the final phase of keratinocyte differentiation, and they are filled with keratins and surrounded by a

lipophilic "cement" consisting of the lipids that fill the extracellular spaces.

We distinguish two different layers of corneocytes, namely the compact layer where the corneocytes, connected to each other by the corneododesmosomes, provide the barrier function, and the desquamating layer where the degradation of these corneodesmosomes causes the phenomenon of desquamation. The corneocytes are thus eliminated continuously by this natural phenomenon or as a result of external aggression. Thus, the renewal of the epidermis is a balance between the loss of superficial cells, corneocytes, and the formation of new epidermal cells in a process of cellular differentiation.

The thickness of the stratum corneum does not decrease with age, but the cohesion of corneocytes becomes unequal, leading to a phenomenon of accumulation contributing to give a xerotic aspect to the integument. Skin aging is accompanied by a decrease in lipid levels in the stratum corneum. As a result, the water content of the subcutaneous tissue decreases with age. There is a significant decrease in the number and average size of keratinocytes, responsible for the reduction of epidermal thickness with age (about 20% over a lifetime), as well as a decrease in dermal-epidermal cohesion resulting in less resistance to trauma.

Within the epidermis, the stratum corneum constitutes the essential element of the cutaneous barrier whereas the dermal structures, for an uninjured skin, participate only slightly in this global barrier function. Thus, aging of the skin, in particular of the stratum corneum, results from factors that may be intrinsic and extrinsic.

The intrinsic factors correspond to the chronological aging. The chronological aging is materialized by a decrease in the proliferation of keratinocytes (which are the cells of the epidermis), and dermal fibroblasts, and therefore their renewal. These senescent cells no longer have the possibility of leaving the G1 phase of the cell cycle and thus of dividing by mitosis. Become resistant to cell death (apoptosis), they accumulate in the dermis and epidermis, and they tend to atrophy.

The extrinsic factors of skin aging can be related to the environment, including friction, washing, detergents, free radicals and climatic aggressions, in particular exposure to the sun and temperature variations, these phenomena being able to contribute to accelerate the degradation of the barrier function of the epidermis and collagen of the dermis.

Various treatments have been envisaged to try to limit the degradation of the skin under the effect of aging, or even to cause rejuvenation of the skin cells to improve the appearance and condition of the skin.

Thus, treatments have been proposed using compositions in the form of serums, creams and lotions containing alpha-hydroxy acids or retinoids, applied regularly to gradually reduce the number of lines and wrinkles, or even topical compositions based on Lys-Thr-Thr-Lys-Ser type penta peptides, promoting the synthesis of collagen and glycosaminoglycans and providing an effect on cutaneous regeneration as described in FR-A-2,783,169. Implants of collagen and hyaluronic acid have also been proposed to hide expression lines around the eyes or mouth, dermabrasion and chemical peels to remove the top layer of damaged skin, cosmetic surgery or a facelift to resuscitate sagging skin, or restructure with a carbon dioxide laser to remove fine lines.

However, these various treatments and compositions are not totdle.tient satisfactory in terms of the control of skin aging and more particularly the restoration of cell differentiation in the stratum corneum.

Olive oil, and in particular virgin olive oil, contains in particular monounsaturated fatty acids (oleic acid) as well as phenolic compounds with antioxidant properties which have the effect of retarding the oxidation of LDL lipoproteins. Among these phenolic compounds, there are phenolic alcohols such as tyrosol and hydroxy-tyrosol, benzoic acids, caffeic and They are esterified with tyrosol and hydroxytyrosol, as well as flavonoids such as flavones and flavonols. Epidemiological studies have shown the health benefits of Mediterranean diets including a high intake of fiber, fruit, vegetables, and olive oil which is the main source of fat - for example, RW Owen et al., Lancet Oncol. (Oct. 20.00) 107-12.

. The patent application JP 2001181198 describes a cosmetic composition having an anti-aging effect and skin lightening, containing a plant extract from the manufacture of olive oil and various excipients. It is also known from DE 102006041486 that a lotion based on olive oil, Cera alba and royal jelly can be used to treat certain dermatological conditions.

P. Andrewes et al., J. Agric. Food Chem. 51: 5, 1415-1420 (2003), have shown that olive oil contains a particular phenolic derivative, namely deacetoxy ligstroside aglycone, which is responsible for its typical taste. G. K. Beauchamp et al. Nature, vol. 437, 45-46 (Sept. 2005), have shown that deacetoxy ligstroside aglycone, also called oleocanthal, contained in virgin olive oil obtained by first cold pressing, has inhibitory properties of COX1 and COX2 enzymes. , that is to say anti-inflammatory properties similar to those of ibuprofen, a molecule used for many years as a non-steroidal anti-inflammatory drug. These properties of oleocanthal are also described in WO 2006122128, and they show that oleocanthal could be considered as a general anti-inflammatory drug, orally, in the same indications as ibuprofen, especially in rheumatology.

Oleocanthal, or deacetoxy-ligstroside aglycone, has been detected in olive oils from various sources, more particularly in virgin olive oil obtained by first cold pressing, at very low concentrations which generally vary from 20 to 200 ppm (mass), or from 0.00-2 to 0.02% by weight, depending the source of the olive oil.

Oleocanthal may be represented by the following general formula (I):

Oleuropein, found in fruits and mainly in olive leaves, is a glycoside represented by the general formula (II) below:

)

The use of oleuropein in food or pharmaceutical compositions for stimulating bone mineralization in humans or animals has been proposed in WO 2004091591. The antiviral activity of certain oleuropein derivatives has also been described in US Pat. US Patent 6,455,580. Derivatives such as oleuropein aglycone, having antioxidant properties, and its dialdehyde form can also be extracted from olive oil.

Other derivatives of interest contained in olive oil include the aldehyde forms of oleuropein aglycone and ligstroside aglycone, represented by formula (III) below,

wherein R is a hydrogen atom or a hydroxy group, and the dialdehyde form of the decarboxymethyl oleuropein aglycone represented by the formula (IV).

Dermatological or cosmetic use of these compounds requires the production of relatively concentrated fractions. In addition, oleocanthal, like most polyphenolic compounds naturally present in vegetable oils, is a very fragile product, easily destroyed by heat and oxidation.

These derivatives, as well as Oleocanthal, participate in the useful properties of olive oil and for this reason various extraction processes have been developed to isolate them or to produce extracts enriched in one or the other. other or more of these derivatives. For example, it is possible to use the extraction method described in patent application FR 2,904,312.

The studies carried out by the Applicant have surprisingly shown that these derivatives, and particularly Oleocanthal, as well as extracts containing them, have interesting properties making it possible to use them in the cosmetic and dermatological field for the control. skin aging, especially the stratum corneum of the epidermis.

The subject of the present invention is therefore the use of an olive oil extract containing oleocanthal and / or a derivative of general formula (A) below.

in which R represents a hydrogen atom or a hydroxyl group, as well as extracts containing them, in cosmetics and in dermatology for the control and regulation of skin aging.

The invention more particularly relates to the use of an olive oil extract containing oleocanthal and / or a derivative for the preparation of cosmetic and / or dermatological compositions for controlling and regulating cutaneous aging.

The subject of the invention is also the combined use of oleocanthal, and / or of derivatives of formula (A) above, and of oleuropein and a cosmetic and / or dermatological composition associating them, useful in particular for ensuring control and regulation of skin aging.

The subject of the invention is also the use of derivatives of formula (A), more particularly oleocanthal, or of olive oil extracts containing them, for the preparation of a medicament for the treatment of ichthyosis and ichthyotic states.

The olive oil extract used in the present invention is an extract enriched in oleocanthal, as indicated below. The studies carried out by the Applicant have shown that the effectiveness of compositions based on derivatives of formula (A) above, in particular oleocanthal, in the cosmetic and / or dermatological treatment of skin aging results from several mechanisms, in particular: a mechanism of inhibition of keratinocyte hyperproliferation reactive to environmental aggressions (to the detriment of the proliferation of keratinocytes); a mechanism for stimulating differentiation of keratinocytosis and regulation of desquamation; a lipid synthesis mechanism.

A study of the effect of oleocanthal, and derivatives according to the invention, on human keratinocytes was made by the "microarray" gene technique on the expression profile of the whole genome with and without prior stimulation by the cytokines IL1 and TNF ALPHA, making it possible to specify the reaction modalities of the product.

This study revealed a novel mechanism of action of oleocanthal that acts by: - inhibiting the specific genes involved in cell hyperproliferation in response to induction by proinflammatory cytokines; stimulating genes directly involved in cell differentiation; by stimulating the genes involved in epidermal lipid metabolism; by reinforcing the homeostatic barrier effect of the skin by an action on the lammellar bodies and the lamellar membrane. The demonstration of these actions demonstrates that oleocanthal is able to control the skin permeability disorders generated by the deficiency of the effect. barrier induced by intrinsic skin aging and aggravated by photoinduced aging.

The oleocanthal, as well as the derivatives described above, are preferably used in the form of olive oil extract enriched with oleocanthal. In the case of the use of an olive oil extract containing oleocanthal in a concentration of at least 10%, the extract generally also contains the dialdehyde of decarboxymethyl oleuropein aglycon, represented by the formula (A) where R is a hydroxyl group. This derivative provides an antioxidant complementary effect useful for the composition of the present invention. Its concentration in the extract can be generally of the order of 5 to 20%.

The amounts used in the compositions of the invention may be between 0.1 mg and 500 mg for the oleocanthal and the derivative, used alone or, preferably, in combination. According to a preferred embodiment of the invention, the composition comprises in combination 10 to 99.5% of oleocanthal and 0.5 to 90% of derivative per 100 g of total composition. According to another preferred embodiment, the composition contains between 0.3 mg and 3 g of olive oil extract containing 30 to 35% oleocanthal and 5 to 20% of dialdehyde of decarboxymethyl oleuropein aglyσone. The compositions that can be used in the present invention can be in any of the usual forms suitable for topical local administration.

Thus, the compositions for topical application may be in the form of oily or hydro-alcoholic solutions, spraying solutions, dispersions, serums, gels or lipogels, suspensions, liquid or semi-liquid emulsions. liquids (for example a milk), solid or semi-solid, shampoo or formulation of the spot-on type. The emulsions may be of the oil-in-water (O / W) or water-in-oil (W / O) type, for example gels or creams. A lipid medium is preferably used, for example a lipophilic solvent such as 1,2-O-isopropylideneglycerol (Solketal) and diethylene glycol monoethyl ether (Transcutol), more compatible in particular with the use of an extract of olive oil. These lipophilic solvents promote the penetration of oleocanthal through the skin. Another penetration adjuvant that can be used advantageously in the invention is tetrahydropiperine obtained from pepper, and is commercially available (Cosmoperine®).

The excipients and carriers that can be used in the compositions according to the present invention are those commonly used in preparations for cosmetic or dermatological use, and they are chosen according to the form of administration chosen. By way of example, mention may be made of gelling agents, emollients, emulsifiers, thickeners, preservatives, softeners, as well as agents for protecting against ultraviolet and perfumes. In a dermatological treatment, the choice of the dose used and the duration of the treatment is determined by the practitioner, but generally a composition dosed between 10 and 500 mg of olcoσαnthal can be used at a rate of or two daily applications for a period of a few days to a few weeks depending on the condition of the skin to be treated.

The tests carried out have shown the effectiveness of the compositions of the invention based on oleocanthal, or olive oil extract enriched in oleocanthal. Thus, formulations containing 0.05 to 0.5% of oleochalhal in the form of galenical preparations for local use on the skin of volunteer patients, without penetration adjuvant, with one or two applications per day. for 15 days, demonstrated a marked improvement in the cutaneous barrier effect manifested by an improvement of the resistance to detergents and degreasers (acetone), a reduction of the insensible loss in water (that is to say the evaporation through the skin, measured with Towl hygrometer).

It can be seen that over the entire surface treated, the skin is more supple and its luster strengthened. Surprisingly, this effect is all the more marked as the age of the patient is high. In addition, the effect is dose-dependent from the threshold of about 0.05%.

These tests show that the compositions according to the invention can be used not only for controlling and regulating cutaneous aging, but also for treating certain skin conditions such as icthyosiform states, orthoergic dermatitis induced by chemical or physical aggression. , and atopic dermatitis.

Examples of oleocanthal-based cosmetic compositions are given below. In these examples all parts and percentages are by weight unless otherwise indicated.

Example 1

A fluid cream for external application is prepared according to conventional techniques and its formulation is as follows. Phase A, B, C, D, and E containing the following constituents (% by weight) were prepared and mixed to obtain a fluid cream. Phase A: 61, 70% Water 0, 10 EDTA disodium (Dissolvine Na2)

2, 00 Pentylene Glycol

1, 50 chlorphenesine 2.00 hydroxyethylacrylate (Sepinov EMT10 B, supplied by Seppic) Phase B:

A composition B containing the following constituents (% by weight) was prepared

4.50% octyldodecanol (Eutanol G)

4.00 Liponate GC (supplied by the company Lipo)

0.11 polysorbate 20 (Tween 20 C, supplied by the company

Masso)

Phase C 5.00 glycerin 1.67 olive oil extract with 33.4% oleocanthal

(provided by Girex)

15,00 90% denatured alcohol,

0.70 Questice +, supplied by Masso Phase D

1.20% KSG 15 (supplied by the company DKSH)

0.10 Dimethicone (Barsil 2001, supplied by society

Barnet

Phase E 0.30% perfume Lutine White 80117 Floressence, supplied by the company Floressence.

This cream can be applied evenly to the skin once or twice a day for 2 to 3 weeks.

Example 2

A lotion having the following composition (% by weight) is prepared:

24.10% PPG-3-myristyl ether (Varionic APM)

57.00 Solketal 15.00 Ethanol at 90 °

0.40 olive oil extract with 30% oléocanthal

2.50 Linoleic acid

1.00 mixture of antioxidant tocopherols (Tocomix L70) Example 3

The following phases A, B, C and D were prepared and mixed to form a serum.

Claims

1. Use of an olive oil extract containing oleocanthal and / or a derivative of general formula (A) below

wherein R represents a hydrogen atom or a hydroxy group, in the preparation of a dermatological drug for the control and regulation of skin aging.

2. Use of an olive oil extract containing oleocanthal and / or a derivative of general formula (A) below

wherein R represents a hydrogen atom or a hydroxy group, in the preparation of a cosmetic composition for the control and regulation of skin aging.

3. Use according to claim 1, characterized in that the drug is administrable topically cutaneous.

4. Use according to any one of claims 1 and 2, characterized in that the oleocanthal and / or the derivative of formula (A) are in the form of olive oil extract enriched in oleocanthal.

B1847WO

5. Use according to claim 4, characterized in that the olive oil extract contains at least 10% by weight of oleocanthal.

6. Use according to claim 5, characterized in that the extract further contains at least 10% by weight of derivative of formula (A) where R is a hydroxyl group.

7. Use according to any one of claims 1 to 6, characterized in that the composition contains between 1 and 500 mg of oleocanthal unit dose.

8. Use according to claim 7, characterized in that the composition further contains between 0.5 and 90 mg of derivative.

9. Use according to any one of the preceding claims, characterized in that it further contains a penetration aid.

10. Use according to any one of the preceding claims, characterized in that it is intended for the treatment of ichthyosis, orthoergic dermatitis and atopic dermatitis.

Cosmetic and / or dermatological composition useful for the control and regulation of skin aging, characterized in that it comprises in combination with oleocanthal and the derivative of general formula (A) according to claim 1, wherein R is a group hydroxyl.

09/03/2009