WO2009044248A2

WO2009044248A2 - Cosmetic and dermopharmaceutical compositions for skin barrier restoration and disorders prevention

Info

Publication number: WO2009044248A2
Application number: PCT/IB2008/002539
Authority: WO
Inventors: Giancarlo Guglielmini; Alessandro Fontana
Original assignee: Sinerga S.P.A.
Priority date: 2007-10-04
Filing date: 2008-09-29
Publication date: 2009-04-09
Also published as: WO2009044248A3; ITMI20071914A1; WO2009044248A8

Abstract

The invention concerns compositions comprising a lipophilic matrix comprising at least 30% by weight of active compounds with respect to the composition weight, wherein said active compounds comprise at least 1 to 10% by weight of lecithin with respect to the composition weight. Such compositions find an advantageous application in cosmetics and in the preparation of formulations for the high-efficacy treatment on both skin barrier restoration and the reactivation of skin microcirculation, as well as for skin pigmentation.

Description

Cosmetic and dermophaππaceutical compositions for skin barrier restoration and disorders prevention

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The present invention concerns cosmetic and dermopharmaceutical compositions comprising a lipophilic matrix and active compounds incorporated therein. The invention further concerns their use in the cosmetic and dermopharmaceutical field. The solubilization of substances by means of lipophilic matrixes is known, which is currently one of the most used techniques in cosmetics and dermopharmaceutics in order to increase the diffusion of the possible incorporated active ingredients. Among the techniques suitable from a cosmetic and dermatological point of view for both actives solubility and stability, there is in particular the technique of emulsifying lipophilic substances thanks to phospholipids and derivatives described in the document WO2004/0447791 and US 20060159633 Al. This technique implies the production of transparent and/or translucent compositions with particle sizes in a range of 5 to 100 ran, obtained through the solubilization in the form of micelles thanks to the use of appropriate emulsifiers and co-emulsifiers and of particular equipments such as high-pressure homogenizers and/or microfluidizers . In the case of atopic dermatitis, characterized by a deteriorated functionality of the barrier, by an increased TransEpidermal Water Loss (TEWL) and by a significant xerosis, as well as in the case of pathologies associated with a local subcutaneous microcirculation disorder, it would be much desirable to provide such active substances in a form allowing a prompt release thereof at a local level and in appropriately effective amounts . Object of the present invention is to provide cosmetic and dermopharmaceutical compositions having improved efficacy in restoring the skin barrier and preventing the disorders thereof, in supporting treatments for the reactivation of subcutaneous microcirculation and in modulating skin pigmentation.

This purpose has been achieved by compositions comprising a lipophilic matrix and active compounds such as disclosed in claim 1. Further advantages and preferred embodiments of the invention are disclosed in the appended claims.

The object of the invention is therefore a composition comprising a lipophilic matrix comprising at least 30% by weight of active compounds with respect to the composition weight, wherein said active compounds comprise at least 1 to 10% by weight of lecithin with respect to the composition weight.

The term "lipophilic matrix" in the present invention means a phospholipid- and lecithin derivative-based matrix in combination with appropriate lipophilic carriers such as medium- and long-chain glycerol esters, medium- and long-chain fatty acid esters, mineral and vegetable oils.

Further characteristics and advantages of the invention will become apparent from the following detailed description made with reference to the exemplary embodiments of the invention given by way of examples and not as a limitation thereof.

According to the present invention, substances used in the cosmetic and dermopharmaceutical field, already known and described in literatures as active on the skin for the treatment and prevention of pathologies linked thereto, thanks to the emulsion with a lipophilic matrix, are incorporated for more than 20% by weight with respect to the composition weight. Preferably, these substances are incorporated for more than 30% by weight with respect to the composition weight. This allows to increase the active compounds release capacity, thus allowing to conveniently reduce the necessary amount of these compounds in the composition itself. In fact, thanks to this technique, it has been noted an increase in the product efficacy when vehicled according to the teaching of the present invention, detectable just on the basis of the decrease in both the hydrophilic and lipophilic active compounds amount. According to a preferred embodiment of the invention, said active compounds comprise disaccharides selected from the group consisting of fructose, saccharose, maltose, glucose, maltodextrin, trehalose and mixtures thereof. Among all the disaccharides, whose bioprotective efficacy is known, trehalose is certainly the one that showed to have a greater capacity to maintain the activity and the vital functions in stress conditions of living organisms by protecting the cells from these osmotic imbalances. Without being bound to any theory, it is believed that its best bioprotective efficacy depends upon its chemical structure which differentiates it from the other disaccharides. It has in fact shown to have this capacity of attracting a greater number of water molecules, trapping and maintaining them available. Trehalose is also known as a cryoprotector . Its high concentration in the tissues of some organisms allows them to survive in the so called "suspended animation" status in environmental stress conditions (lack of water and at very high temperatures) . These organisms, once rehydrated, resume their normal life cycle, without showing any damage.

Recent results have shown how disaccharides bioprotective efficacy derives from a combination of interactions at a structural, physiological and molecular level due to the particular mechanisms of interaction with water molecules. The trehalose/H₂θ solution shows a higher structural resistance to temperature changes as compared to, for example, maltose and sucrose. Other results show that trehalose, apart from significantly modifying the structural properties of water, forms with the latter an entity having a character more able to furtherly protect biological structures. For this reason, trehalose is used in cosmetic products as a stabilizer of easily degradable substances (e.g. Vitamin C) and also as a functional substance as skin moisturizer, intended as moisturizing container. In fact, it enwraps water molecules making them bioavailable in time, protecting the skin from the most common pollutants and slowing down the ageing processes.

Other disaccharides suitable for the objects of the present invention are fructose, saccharose, maltose, glucose and maltodextrin. In lipophilic matrixes of the present invention, these hydrophilic active compounds become a sole cosmetic and dermopharmaceutical ingredient able to simulate the skin barrier and its chemico-physical characteristics. Preferably, the composition of the present invention further comprises ceramides, cholesterol or mixtures thereof. More preferably, the composition of the present invention comprises 1 to 10% by weight ceramides, 5 to 30% by weight trehalose and 1 to 10% by weight cholesterol, with respect to the composition weight. Still more preferably, it comprises 1 to 5% by weight ceramide 2, 10 to 20% by weight trehalose and 1 to 5% by weight ^' cholesterol, with respect to the composition weight.

The possibility to have in the same cosmetic ingredient the combination between compounds of the same class of functional lipids, such as cholesterol, ceramides, and free fatty acids and precursors thereof, represents a valid support for the restoration of an altered skin barrier. In particular, as skin barrier alterations are usually linked to skin dryness conditions, when the active ingredient is associated to a humectant sugar agent such as trehalose, a substantial increase of the moisturizing rate at the stratum corneum level is observed. As will be apparent from the following examples, the achieved experimental results showed that the topic application of a product obtained from the combination in nanoparticles thanks to this particular solubilization technique described in US 20060159633 Al increases skin capacitance (i.e. skin moisturizing level) up to 40% and lowers the TEWL (i.e. transepidermal water loss) by 15% in 2 weeks as compared with its placebo. This allowed to observe by dermatological analysis, a normalization of skin barrier restoration rate. Consequently, with the same treatment it is possible to obtain, on one hand, the restoration of a disorganized barrier thanks to the renovation of intercellular lipids and, on the other hand, an immediate moisturizing effect on the superficial stratum corneum is obtained. Therefore, the composition of the present invention showed to be an ideal carrier, as it provides an extremely advantageous and convenient combination of ingredients suitably equal and compatible with the composition of skin hydrolipidic surface, advantageously allowing a reduction of the amount of necessary active ingredient.

Thereby, through the same treatment it is possible to simultaneously restore the altered stratum corneum by both rearranging the intercellular lipid network and providing an immediate moisturizing effect on the superficial stratum corneum. Additionally, it was observed that restoring the barrier function of the status corneum by using the composition according to the present invention not only allows to improve skin appearance, but also to advantageously reduce skin penetration of sensitising agents and chemical agents and at the same time to reduce the release of pro-inflammatory mediators induced by an altered barrier function. According to another preferred embodiment of the invention, the composition active compounds comprise ethyl ximenynate. Preferably, the composition of the invention comprises 10 to 50% by weight ethyl ximenynate, with respect to the composition weight. Still more preferably, it comprises 15 to 25% by weight ethyl ximenynate, with respect to the composition weight.

The topic ^'application of a lipophilic ingredient combination, such as ethyl ximenynate, incorporated into a phospholipid-containing lipophilic matrix showed instead vasodilatatory characteristics five times higher than the incorporated active ingredient. It is in fact an example of lipids incorporation into the matrix characterized by very high efficacy. This novel composition, obtained also in this case by solubilisation into a lipophilic matrix, incorporating more than 30% of active ingredients, showed to be able to improve the superficial blood microcirculation.

Among the lipophilic substances suitable for the purposes of the present invention, significant results were achieved with the incorporation of essential oils. Therefore, the compositions according to the present invention preferably also comprise essential oils obtained from aromatic officinal plants, such as mint, chamomile, orange, lemon, thyme, basil and the like, skin eudermic and healing oils, such as macadamia, olive, jojoba, avocado, sunflower, paprika, green tea oils, and vitamins, such as vitamin E and derivatives thereof, vitamin A and derivatives thereof, bisabolol, lanoline, linolenic acid and polyunsaturated fatty acid (abbr. PUFA), ceramides and the like. In the most preferred embodiment of the invention, the composition comprises a pure product, obtained by consecutive extractions from Ximenia triandra and Olax dissltiflora, particularly from the point of view of yield and stability. Such product is known and described in the prior art (EP 0304603 Bl) for its capacities to interfere with cyclooxygenases and lipoxygenases and phospholipases A2, i.e. enzymes entering the cycle of arachidonic acid. Its interaction leads to an increase in skin microcirculation. Furthermore, the purified lipophilic fraction of Olax dissitiflora (ethyl ximenynate) also acts as a PPARs (Peroxisomal Proliferator Activated Receptors) agonist, thus playing a significant role in the increase of epidermis differentiation, of collagen synthesis levels as well as of lipogenesis.

Morphological, histochemical, biochemical and ultrastructural modifications of the skin, in patients suffering from obesity are always associated to pathological alterations and consequent disorders of skin microcirculation, of both blood and lymphatic circulation system. Furthermore, they are associated with oedema and fibrosis of the adipocyte and are considered as the primary event in the pathogenesis of cellulitis and of blemishes associated thereto, i.e. of the so-called "orange-peel" or "mattress-skin" aspect of legs skin. By acting on the modulation, i.e. by improving the local microcirculation of the affected sites, a positive efficacy is certainly obtained in the therapeutic approach of disorders connected to blood microcirculation alteration.

In fact, thirty minutes following to topic application, after measurements of blood flow, carried out by Laser Doppler Flowmeter, a significant increase in the blood flow itself is noted, indicating that these compositions are particularly effective in cosmetic formulations for the amelioration of microcirculation disorders at the capillary vessels level such as cellulitis, localized adiposity, heavy legs, chilblains and streaks. In a further preferred embodiment of the invention, the compositions comprise lipoaminoacids as active compounds, i.e. compounds obtained by condensation between medium- and long-chain fatty acids and amino acids, more preferably caproyl tyrosine. These compositions, in fact, showed to be advantageous adjuvants in the increase of skin pigmentation.

Advantageously and preferably, the composition according to the present invention further comprises glycerine, medium- and long-chain triglycerides, linear or branched esters of saturated and unsaturated medium- and long- chain fatty acids and mixtures thereof. An advantageous aspect of these compounds is to obtain clear or translucent lipophilic formulations used in sunscreen cosmetic products without adding further ethoxylated surfactants . In a preferred embodiment, the composition according to the present invention is in the form of a gel. According to another aspect, the present invention concerns a preservative-free cosmetic formulation comprising the composition according to the present invention and one or more cosmetic excipients. According to still another aspect, the present invention concerns a preservative-free dermopharitiaceutical formulation comprising the composition according to the present invention and one or more dermopharmaceutical excipients.

Preferably, the formulations according to the present invention are in the form of a cream, a gel, a lypogel, a lotion or an emulsion. The following are exemplary embodiments, herein given by way of examples and not as a limitation of the compositions and the relative formulations of the invention. Unless otherwise stated, all the amounts present in the following examples are % by weight. Examples 1-10 HIGH-EFFICACY SKIN BARRIER RESTORERS

Compositions in the form of a gel were obtained by encapsulation into lecithin blisters with high-pressure homogenization technique of trehalose, ceramides and cholesterol .

Each of the above-listed compositions also comprises glycerine, octyldodecanol and water (q.s. at 100% by weight) . The compositions are in the form of a moisturizing, emollient and protective gel.

The compositions showed to be efficient for all the skin disorders associated with a skin barrier damage (atopic dermatitis, contact and allergic dermatitis, psoriasis) . A skin protection (cleansers, creams, gels) for dry skins and/or skins with hyperkeratosis is in fact provided. A decrease in the transepidermal water loss (TEWL) was observed. If dissolved in 1% water, the compositions of examples 1- 10 form dispersions having an average particle size of 100 to 200 nm.

In preservative-free cosmetic formulations according to the present invention, the compositions of the above examples can be present in the following amounts: Emollient emulsions-gels 1% to 3% W/0 emulsions for dry skins 1% to 3% Moisturizing gels 1% to 3% Barrier creams 1% to 3%

The compositions can be added at the end of the preparation process of the finished cosmetic formulations, i.e. after the cooling step in case of emulsions .

Examples 11-20

HIGH-EFFICACY MICROCIRCULATION MODULATORS

Compositions in the form of a gel were obtained by encapsulation into lecithin blisters with high-pressure homogenization technique of ethyl ximenynate.

Each of the above-listed compositions also comprises glycerine and capric/caprylic triglycerides (q.s. to 100% by weight) . The compositions showed to be efficient as adjuvants in the treatment of troubles linked to an altered skin microcirculation and as skin protector (cellulitis, local adiposity) in the form of creams, gels, capillary lotions. If dissolved in 1% water, the above compositions form dispersions having an average particle size of 100 to 200 nm.

In preservative-free cosmetic formulations according to the present invention, the compositions of the above examples can be present in the following amounts: Emulsions-gels for heavy legs 1% to 3% O/W emulsions for chilblains 1% to 3% Lipolytic lypogels 1% to 3%

Anti-hair-loss lotions 1% to 3% The compositions can be added at the end of the preparation process of the finished cosmetic product, after the cooling step in case of emulsions. Examples 21-30 HIGH-EFFICACY SKIN PIGMENTATION ADJUVANTS Compositions in the form of a gel were obtained by encapsulation into blisters made of Lecithin with high- pressure homogenization technique of caproyl tyrosine and mint essential oil.

Each of the above-listed compositions also comprises glycerine, sorbitol, capric/caprylic triglycerides (q.s. at 100% by weight) .

The compositions showed to be efficient as adjuvants in increasing skin pigmentation.

If dissolved into 1% water, the above compositions form dispersions having an average particle size of 100 to 200 ran.

In cosmetic formulations according to the present invention, the compositions of the above examples can be present in amounts of 1% to 10%.

The compositions can be added at the end of the preparation process of the finished cosmetic product, after the cooling step in case of emulsions.

As it can be seen from the above reported examples, the compositions according to the present invention showed to be extremely efficient in both cosmetic and dermopharmaceutical fields, achieving results such as the improvement of an altered superficial blood circulation, the equilibration of skin barrier by controlling skin moisturization and protection, as well as an increase of skin pigmentation. In fact, the stratum corneum is a dynamic structure resulting from the desquamation and cornification process, strictly linked to each other. Its formation is controlled in response to the alterations of the barrier function caused by some skin disorders. The dermatological treatment according to the present invention implies the use of intercellular lipids playing a key role in maintaining and modulating the efficiency and fortification of the stratum corneum barrier effect. In fact, the combination and incorporation of intercellular lipids restoring an existing condition of imbalance of the skin barrier matrix, allow to obtain a restoring agent of the intercellular lipid network with an immediate moisturizing effect to the stratum corneum, through the control of skin moisturization and protection.

Claims

1. A composition comprising a lipophilic matrix comprising at least 20% by weight of active compounds with respect to the composition weight, wherein said active compounds comprise at least 1 to 10% by weight of lecithin with respect to the composition weight.

2. A composition according to claim 1, comprising a lipophilic matrix comprising at least 30% by weight of active compounds with respect to the composition weight.

3. A composition according to claim 1 or 2, wherein said active compounds comprise disaccharides selected from the group consisting of fructose, saccharose, maltose, glucose, maltodextrin, trehalose and mixtures thereof.

4. A composition according to claim 3, wherein said active compounds comprise trehalose.

5. A composition according to any one of claims 1-4, further comprising ceramides, cholesterol and mixtures thereof.

6. A composition according to claim 5, comprising 1 to 10% by weight ceramides, 5 to 30% by weight trehalose and

1 to 10% by weight cholesterol, with respect to the composition weight.

7. A composition according to claim β, comprising 1 to 5% by weight ceramide 2, 10 to 20% by weight trehalose and 1 to 5% by weight cholesterol, with respect to the composition weight.

8. A composition according to any one of claims 1-7, wherein said active compounds comprise ethyl ximenynate .

9. A composition according to claim 8, comprising 10 to 50% by weight ethyl ximenynate, with respect to the composition weight.

10. A composition according to claim 9, comprising 15 to 25% by weight ethyl ximenynate, with respect to the composition weight.

11. A composition according to any one of claims 1-10, wherein said active compounds comprise lipoaminoacids .

12. A composition according to claim 11, wherein said lipoaminoacids are caproyl tyrosine.

13. A composition according to any one of claims 1-12, further comprising essential oils, vitamins and mixtures thereof.

14. A composition according to any one of claims 1-13, further comprising glycerine, medium- and long-chain triglycerides, linear or branched esters of saturated and unsaturated medium- and long-chain fatty acids and mixtures thereof.

15. A composition according to any one of claims 1-14, in the form of a gel.

16. A cosmetic formulation comprising the composition according to any one of claims 1-15 and one or more cosmetic excipients.

17. A dermopha-rmaceutical formulation comprising the composition according to any one of claims 1-15 and one or more dermopharmaceutical excipients.

18. A formulation according to claim 16 or 17, comprising 1 to 3% of the composition according to any one of claims 1 to 15.

19. A formulation according to any one of claims 16-18, in the form of a cream, a gel, a lypogel, a lotion or an emulsion.

20. A use of a composition according to any one of claims 1-15, as cosmetic component.

21. A use of a composition according to any one of claims 1-7, 13-15, for the preparation of a dermopharmaceutical formulation for the high-efficacy restoration treatment of skin barrier.

22. The use of a composition according to any one of claims 8-10, 13-15, for the preparation of a dermopharmaceutical formulation for the local high- efficacy topic treatment of microcirculation.

23. The use of a composition according to any one of claims 11-15, for the preparation of a dermopharmaceutical formulation for increasing skin pigmentation.