WO2006105805A1

WO2006105805A1 - Delaying skin ageing and disorders caused by skin ageing by suppression of angiotensin ii production or activity

Info

Publication number: WO2006105805A1
Application number: PCT/EP2005/003666
Authority: WO
Inventors: Miso Sabovic
Original assignee: Miso Sabovic
Priority date: 2005-04-07
Filing date: 2005-04-07
Publication date: 2006-10-12

Abstract

The present invention relates to the field of ageing of the skin, particularly to the prevention and/or treatment of skin ageing and disorders caused by skin -ageing. The use of a topical applicable composition is envisaged, which comprises three or more active ingredients to reduce or suppress skin ageing and disorders associated with ageing and their symptoms, such as wrinkles.

Description

DELAYING SKIN AGEING AND DISORDERS CAUSED BY SKIN AGEING BY SUPPRESSION OF ANGIOTENSIN II PRODUCTION OR ACTIVITY

The present invention relates to the field of ageing of the skin, particularly to the prevention and/or treatment of skin ageing itself and disorders caused by skin ageing. The use of a topical applicable composition is envisaged, which comprises three or more active ingredients to reduce or suppress skin ageing and disorders associated with skin ageing and their symptoms, such as wrinkles.

Skin ageing is a part of the complex process in the human body. Aged skin, with its specific characteristics like wrinkles, is one of the most visible consequences of the ageing process and for most of the affected individuals disturbing and undesired. In general, skin is predisposed to two main ageing processes, the "internally driven ageing" (skin ageing due to genetic predetermination and damage brought about by metabolic side products) and the "externally driven ageing" (skin ageing due to damage caused by UV radiation, cigarette smoke, air pollution, etc.). The complex process of skin ageing is so far only partially understood. It seems that three different mechanisms are involved in skin damage and act through numerous pathways, but their common point of action is an increased oxidative damage of cellular and extra cellular components: nuclear and mitochondrial DNA, cellular and matrix proteins and lipid membranes, destruction and impeded collagen synthesis.

The literature and available data suggest that the major mechanisms responsible for skin ageing are increased oxidative stress, UV radiation and the overexpression of the local renin- angiotensin (RAS) system in the skin.

An increased oxidative stress in the skin occurs preliminary due to aggressive free radicals, like singlet oxygen or ozone, which are generated in the course of normal physiological processes, including aerobic metabolism and inflammatory response, but may inflict cellular damage as well, when the radical generation is increased and antioxidant defence mechanisms are overwhelmed. Oxidants and antioxidants play an important role in maintaining a balance between free radicals produced by metabolism or derived from environmental sources. Intrinsic ageing is mainly controlled by progressive telomere shortening caused by low-grade oxidative damage to telomeres and other cellular constituents, as a consequence of aerobic cellular metabolism. Cellular antioxidants may change their redox state, be targeted for destruction, regulate the oxidative process involved in signal transduction, affect gene expression and pathways of cell proliferation and death. The overall skin low molecular weight antioxidant (LMWA) capacity has been evaluated during the ageing process and following exposure to oxidative stress. It has been found that the skin possesses an extremely efficient and unique antioxidant activity that seems to be more effective than that of other tissues. During the ageing process, a significant decrease in the level and activity of the water-soluble LMWA (uric acid, ascorbic acid) was detected, while no change or even a slight increase was recorded for the lipophilic LMWA. Similar results were obtained following exposure to oxidative stress. A significant decrease in the water soluble LMWA was recorded in all stress induced procedures, indicating a common mechanism of response. It has also been shown that along with the reduction in total water soluble antioxidant activity there is an accumulation of oxidized adducts. This was observed both on the surface and in deeper layers of the skin. It has been found that the skin releases LMWA from its surface. This secretion phenomenon occurred in an age dependent manner. Thus, oxidative stress is increased on the one hand by ageing and has on the other hand an important role in skin ageing, since the skin possesses a unique and effective antioxidant defence.

As the outermost barrier of the body, the skin is also directly and frequently exposed to a pro- oxidative environment, including solar ultra-violet radiation, namely UVA and UVB radiation, and air pollution. UV irradiation alters the expression of multiple genes that encode functions to repair DNA damage, arrest cell growth, and induce apoptosis. UV irradiation induces oxidative stress and inflammation mediated by reactive oxygen radicals, lipid peroxidation, liberation of arachidonic acid from membrane phospholipids and formation of prostaglandins and leucotrienes, and consequently to photo ageing over a long period. UV- induced infiltrating leukocytes contribute to developing oxidative stress in UV-irradiated skin. UV induces the matrix metalloproteinases, collagenase, gelatinase, and stromelysin, which degrade skin connective tissue and may contribute to photo ageing. UV irradiation also reduces production of type I procollagen, the major structural protein in human skin. The skin is equipped with an elaborate system of antioxidant substances and enzymes that includes a network of redox active antioxidants. Skin exposure to UV and ozone alone and in combination resulted in a significant potentiation of UV-induced vitamin depletion.

Recent studies have also shown that numerous tissues, particularly the skin, and organs contain their own (locally generated or absorbed from the blood) components of renin- angiotensin system (RAS) and exhibit their own corresponding activities. Such an intrinsic angiotensin-generating system performs a specific tissue function in the body, frequently via regulatory mechanisms of a paracrine, autocrine or intracrine nature. Angiotensin II has long been regarded to be primarily responsible for the regulation of blood-pressure and of volume- and electrolyte-homeostasis. The local renin-angiotensin (RAS) system has been shown to be responsive to various stimuli of physiological and pathophysiological importance. Such trophic actions have already been observed in tissues not belonging to the renal or cardiovascular systems, including skin. Moreover, the locally generated angiotensin peptides have multiple and novel actions, including cell growth, , apoptosis, reactive oxygen species generation, hormonal secretion, pro-inflammatory, and pro-fibrogenic actions, as well as vasoconstriction. Evidence for the role of angiotensin II in the skin is so far scanty and mainly based on the demonstration of angiotensin receptors on cultured human keratinocytes and in subcutaneous tissue of rats. ATI and AT2 receptors were found within the epidermis and in dermal vessel walls. The same expression pattern was found for angiotensinogen, renin and angiotensin-converting enzyme (ACE). All these components could further be demonstrated at rnRNA level in cultured primary keratinocytes, melanocytes, dermal fibroblasts and dermal microvascular endothelial cells. Although almost every single component of the RAS system has already been identified in skin of one or another species, comprehensive data regarding the skin RAS system as a whole within one particular species, especially in man, are still lacking. Angiotensin II, a vasoconstrictive peptide, is reported to have profibrotic activity as a result of induction of the extracellular matrix. The profibrotic process also takes place in the skin as well as in other organs such as the heart and kidney, which have been extensively studied. On the basis of the available data, it may be assumed that an overexpressed skin RAS system importantly contributes to skin ageing. The main mechanism for such damage could be increased oxidative stress, with all its damaging effects on cells and matrix components.

Currently used compositions for the treatment or prevention of ageing of the skin include for example an agent with elastase inhibiting activity capable to maintain the tautness and elasticity of the skin and to maintain a youthful state of the skin (c.f. EP 0 919 223). The anti ageing agent is proposed for use in all kind of cosmetics, e.g. basic cosmetics and comprises a natural product extract at low concentration.

WO 2004060288 relates to topical compositions with an active ingredient derived from a plant or plant material for improving the appearance of skin, especially by alleviating skin irritation. The topical compositions contain at least one natural plant extract that inhibits COX-2 enzyme, NGF protein and/or TNF-alpha protein activity. The plant extract may be isolated for example from Ilex purpurea Hassk, Ligusticum chiangxiong, Asmunda japonica, Butea frondosa or Ligusticum lucidum.

In FR 2837702 a composition particularly suitable for the preparation of a night-cream is disclosed. The cream exhibits antioxidant effects and may be used for the prevention and or treatment of symptoms assigned to photo ageing. Three active components are contained in the cream, such as the extracts of Mirabilis jalapa, of brown algae, like Laminaria cloustoni, and of tangerines, e.g. Citrus reticulata.

However, the above-mentioned compositions are still deficient in that their efficacy for the intended purpose is poor. Hence there is a need for an improved regimen for treating and/or preventing the ageing of skin.

Thus, the problem of the present invention resides in the provision an improved treatment regimen, wherein said regimen bestows protection against an ageing of the skin. This objective has been achieved by the use a topical composition, which comprises a mixture of at least three constituents. Each of said constituents exhibits the capacity to beneficially influence one or more of the above three mechanisms responsible for ageing of the skin. The present invention discloses, in the form of a topical applicable formulation, the use of ACE-inhibitors or angiotensin receptor blockers in combination with at least one antioxidant vitamin and at least one compound conferring protection towards UV radiation.

In combination said constituents surprisingly show synergistic effects towards the prevention and/or treatment of skin ageing and specific skin disorders related to ageing. Without wishing to be bound by any theory, it is presently assumed that the synergistic effects instigated by the use of the different combined constituents in one composition reside in that the compound suppressing angiotensin production concurrently impedes the generation of free radicals, whereas the antioxidant functions as a radical scavenger, which facilitates the elimination of already generated radicals. These two complementary mechanisms result in a significant reduction of oxidative stress in the skin and are additionally supported by a sunscreen compound obstructing energetic UV radiation, which radiation in turn could promote the generation of free radicals. The particular effect of the present composition resides in the combination of compounds preventing the generation of free radicals at different metabolic stages and a compound, which intercepts already generated free radicals. Thus, the ageing process of skin is delayed or slowed by the above pharmacological treatment, which is properly focused on the three main pathological mechanisms.

According to a first embodiment of the present invention, the use of a topical applied composition for the preparation of a medicament for the prevention and/or treatment of a skin disorder caused by ageing is envisaged. Said composition comprises as active ingredients a compound suppressing angiotensin II production or activity, at least one antioxidant and at least one barrier compound, which acts as a sunscreen.

The term ageing is presently used to describe the changes in appearance and/or function of human skin as a result of repeated exposure to sunlight, and especially regarding the development of wrinkles as characteristic symptoms and other changes in the appearance of the skin, such as sunburns. This effect commonly occurs in skin that is habitually exposed to sunlight, such as the face, ears, bald areas of the scalp, neck, forearms and hands.

The signs of ageing or photo ageing of the skin may be induced or caused by intrinsic factors or extrinsic factors, e.g., chronological ageing and/or environmental damage. These signs may result from processes which include, but are not limited to, the development of textural discontinuities such as wrinkles and coarse deep wrinkles, skin lines, crevices, bumps, large pores (e.g., associated with adrenal structures such as sweat gland ducts, sebaceous glands, or hair follicles), or unevenness or roughness, loss of skin elasticity (loss and/or inactivation of functional skin elastin), sagging (including loss and/or damage to functional subcutaneous muscle tissue and including puffmess in the eye area and jowls), loss of skin firmness, loss of skin tightness, loss of skin recoil from deformation, discoloration (including under eye circles), blotching, shallowness, hyper pigmented skin regions such as age spots and freckles, keratoses, abnormal differentiation, hyperkeratinization, elastosis, collagen breakdown, and other histological changes in the stratum corneum, dermis, epidermis, the skin vascular system (e.g., telangiectasia or spider vessels), and underlying tissues, especially those proximate to the skin.

Topical compositions according to the present invention generally contain a base or carrier, such as an ointments, creams, salves, lotions, gels, sprays, aerosols, patches, solutions, suspensions and emulsions, that allow the application of the active ingredients on the skin. Compositions suitable for topical application to the skin preferably take the form of an ointment, cream, lotion, paste, gel, spray, aerosol, or oil. Carriers which may be used include vaseline, lanolin, polyethylene glycols, alcohols, transdermal enhancers, and combinations of two or more thereof. Compositions suitable for transdermal administration may be presented as discrete patches adapted to remain in intimate contact with the epidermis of the recipient for a prolonged period of time.

The compound, capable to suppress the angiotensin production or function, is preferably selected from the group consisting of an angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers. Since basic mechanisms of skin ageing rely on increased oxidative stress and overexpression of the RAS system in the skin, the use a topical angiotensin receptor blockers (ARBs) or angiotensin-converting enzyme (ACE) inhibitors have proven beneficial effects in the present composition. In contrast to antioxidants, such as vitamins, ARBs and ACE inhibitors reduce the production of free radicals and do not scavenge them like the antioxidant vitamins. An ARB or ACE inhibitor is a highly effective constituent of the present formulation. Different representatives of ARBs or ACE inhibitors, which are well known to the skilled person, may be chosen for the present composition.

According to another embodiment of the present invention, the ARB is preferably selected from the group consisting of valsartan, losartan, irbisartan, and ACE inhibitor from the group consisting of perindopril, ramipril and trandolapril. Due to an improved uptake and bioavailability, said lipophilic agents exhibit a higher effectiveness than other ARBs and ACE inhibitors. Said ARBs and ACE inhibitors are also skin tolerant, non-allergic, well penetrating, chemically stable and bioactive.

A preferred ARB is the compound valsartan, which reveals highest specificity for the inhibition of Angiotensin II ATI receptors in different tissues compared to other ARBs. Additionally, valsartan has an anti-inflammatory capacity. In the mouse model, it has been shown that valsartan specifically inhibits overproduction of collagen in the extracellular matrix of skin. Thus, valsartan directly and indirectly affects increased oxidative stress.

According to another preferred embodiment said at least one antioxidant is a vitamin, which is preferably selected from the group consisting of Vitamin A, Vitamin C and Vitamin E. Likewise, derivatives of said vitamin(s) may be included in the present composition.

Vitamin A or retinoids, either naturally occurring or synthetic, are defined by their ability to bind nuclear retinoid receptors of the steroid/thyroid superfamily. Their protean but key function in physiology is control of cellular proliferation and differentiation. In the treatment of photo ageing, numerous large-scale, double-blind, placebo-controlled trials have shown the efficacy of topical retinoin. Topical retinoids, namely retinoin, prevent and repair clinical features of photo ageing; these processes are facilitated by an ability to prevent loss of collagen, and stimulate new collagen formation in the papillary dermis of sun-exposed skin. Emerging evidence indicates that intrinsic ageing of the skin shares several mechanistic features with photo ageing. However, as retinoin remains a prescription drug, over-the- counter products mainly utilize the vitamin A derivatives retinol and retinyl palmitate. These forms are not biologically active until enzymatic conversion to the principal active metabolite, retinoic acid. Research data suggest that skin ageing results from the interplay of extrinsic damage by UV radiation (resulting in increased oxidative stress), intrinsic increases in collagen-degrading matrix metalloproteinases, and decreased collagen synthesis. Retinol plays important roles in countering all these mechanisms.

Vitamin C or L-ascorbic acid, the biologically active form of vitamin C, has well-established roles in the human body as an antioxidant and as a cofactor for collagen synthesis. Ascorbate participates in the hydroxylation of procollagen, and studies show that it may also stimulate collagen synthesis directly by activating its transcription and stabilizing procollagen mRNA. The physiological mechanisms affected by vitamin C are likely to include the increased production of collagen, as well as the decreased production of matrix metalloproteinase, an enzyme that enhances dermal collagen degradation. Ascorbic acid may also have some anti- inflammatory effects. Further, its role as an antioxidant gives ascorbate similar photo protecting properties as vitamin E by neutralizing UVB-generated free radicals. Beyond its well-known antioxidant effects vitamin C may also have cytoprotective effects. As an antioxidant, ascorbic acid is the body's main water-soluble, non-enzymatic scavenger of free radicals, enabling it to function efficiently in aqueous compartments. In addition to these roles in the maintenance of skin health, ascorbic acid also helps to regenerate the oxidized forms of α-tocopherol. Topically applied l-ascorbic acid increased ascorbate levels in skin up to 25 times. Stable and hydrophobic solutions of ascorbic acid consist of the molecule in its non-ionized form at a low pH.

Vitamin E, or α-tocopherol, is a lipid-soluble antioxidant, which plays key roles in protecting cellular membranes from lipid peroxidation by free radicals. These free radicals contribute significantly to the environmental or extrinsic ageing of skin, especially UV-mediated damage. Although the human skin possesses various intrinsic defence systems which help to mitigate these types of oxidative damage, both excessive and chronic exposure to free radicals can deplete the body's defence, α-tocopherol modulates this damage by scavenging free radicals and lipid peroxyl radicals. Vitamin E is distributed in a gradient fashion in the stratum corneum of healthy skin, with the highest levels in the deepest layers and the lowest levels closest to the surface, α-tocopherol is further the major antioxidant in the human epidermis and its depletion is an early and sensitive marker of environmental oxidative damage. Vitamin E is available most commonly as α-tocopherol or tocopherol acetate. However, as with other vitamins and antioxidants applied topically, success of delivery and clinical efficacy are separate and crucial elements of an effective anti ageing treatment. The topical application of vitamin E increases stratum corneum hydration and enhances water- binding capacity. The protective effects of vitamin E against photo ageing have been already demonstrated in various animals and in vitro skin models.

Said least one barrier compound is preferably a UV filter, which is more preferably selected from the group consisting of UVA and UVB filters.

The solar radiation responsible for photo ageing is generally divided into ultraviolet light A (UVA) and ultraviolet light B (UVB) radiation. UVB encompasses the solar spectrum from 290 to 320 nanometres (nm), and UVA encompasses the spectrum from 320 to 400 nm. Thus, UVA radiation includes longer wavelengths, allowing deeper penetration into the skin. UVB rays are important contributors to wrinkling, skin disease, and skin cancer, but recent studies have shown that UVA radiation is equally or even more important. In the mouse model, it has been shown that sagging of the skin is produced by UVA exposure, and that this sagging can be reduced or prevented with a sunscreen agent including a UVA and/or UVB filter.

Suitable UVA and UVB filters are known to the skilled person. UVA filters are e.g. di- benzoylmethane derivatives, particularly l-(4'-tert-butylphenyl)-3-(4'-methoxyphenyl)pro- pane-l,3-dione and l-phenyl-3-(4'-isopropylphenyl)propane-l,3-dione. Examples of suitable UVB filters comprise 3-benzylidenecamphor derivatives such as preferably 3-(4-methyl- benzylidene)camphor, aminobenzoic acid derivatives, such as 2-ethyl-hexyl 4-(dimethyl- amino)benzoate and amyl 4-(dimethyl-amino)benzoate and benzophenone derivatives, such as 2-hydroxy-4-methoxybenzophenone, 2-hydroxy-4-methoxy-4'-methylbenzophenone and 2,2'-dihydroxy-4-methoxybenzoρhenone.

In another embodiment, the compound suppressing angiotensin II production or activity is contained in an amount of about 0.25 to 7.5 % by weight, preferably in an amount of about 0.5 to 2.5 % by weight and more preferably in an amount of about 1.0 to 2.0 % by weight.

hi still another embodiment said at least one antioxidant is contained in an amount of 0.5 to 25% by weight. In case of vitamin A and vitamin E said at least one antioxidant is preferably contained in an amount of about 0.5 to 15 % by weight, more preferably in an amount of about 1.0 to 5.0 % by weight and most preferably in an amount of about 2.5 to 5.0 % by weight. If vitamin C is included, preferably an amount of about 1 to 25 % by weight, more preferably an amount of about 3 to 10 % by weight and most preferably an amount of about 3 to 7 % by weight is envisaged.

In an embodiment said least one barrier compound, which is capable to act as sunscreen, is contained in an amount of 0.5 to 15 % by weight, preferably in an amount of about 0.5 to 5.0 % by weight and more preferably in an amount of about 2.0 to 5.0 % by weight.

The concentration of active compounds in the topical composition will nevertheless depend on e.g. absorption, inactivation, excretion rates, the dosage schedule and amount administered as well as other factors known to those of skilled in the art. The other ingredients to produce a topical applicable composition, such as an ointment, cream, salve, lotion or gel are also well known to the skilled person and may be formulated depending on the desired consistency and other properties envisaged.

The following examples illustrate the invention without limiting it thereto. Examples

1. Preparation of 1 g of adipoid ointment A:

15 mg valsartan,

30 mg vitamin A,

30 mg vitamin C,

30 mg vitamin E, 30 mg 2-hydroxy-4-methoxybenzophenone,

100 mg macrogolstearate,

100 mg 1000-cetylstearylalcohol,

100 mg 1 ,2-propandiole, and

565 mg vaseline (white).

Followed by blending to achieve a homogenous consistence.

2. Preparation of 1 g of adipoid ointment B:

25 mg valsartan,

50 mg vitamin A,

50 mg vitamin C,

50 mg vitamin E, 25 mg 2-hydroxy-4-methoxybenzophenone,

25 mg l-phenyl-3-(4'-isopropylphenyl)propane-l,3-dione,

100 mg macrogolstearate,

100 mg 1 OOO-cetylstearylalcohol,

100 mg 1 ,2-propandiole, and 475 mg vaseline (white).

Followed by blending to achieve a homogenous consistence.

3. Assay for the influence of the active ingredients on cell growth and number of juvenile cells

Pre-characterized rat smooth muscle cells, deposited with DSM-Deutsche Sammlung von Mikroorganismen and the Accession No. DSM ACC 132, have been used to study the influence of the combined active ingredients. The tissue cells were grown in 96-well microtitreplates, containing 150 μl/well 80% Dulbecco's MEM/20% FBS medium, preheated at 37⁰C and 5% CO₂ to a density of ≥IOOO cells/well up to 1500 cells/well, determined by means of a Thoma chamber under a light microscope. 80% Dulbecco's MEM/20% FBS medium (cf. DSMZ catalogue, Human and Animal Cell Lines, 1999) represents also the medium for cell growth and was changed daily.

The influence of the active ingredients of ointments A and B have been tested by preparing solutions containing 15 mg valsartan, 30 mg vitamin A, 30 mg vitamin C, 30 mg vitamin E, 30 mg 2-hydroxy-4-methoxybenzophenone in 10 ml 80% Dulbecco's MEM/20% FBS medium (solution A) and 25 mg valsartan, 50 mg vitamin A, 50 mg vitamin C, 50 mg vitamin E, 25 mg 2-hydroxy-4-methoxybenzophenone and 25 mg l-phenyl-3-(4'-isopropylphenyl)propane-l,3- dione in 10 ml 80% Dulbecco's MEM/20% FBS medium (solution B). Dissolving of the components in 80% Dulbecco's MEM/20% FBS medium was promoted by using an ultrasonic- bath at ambient temperature. As negative control RPMI medium (solution C) was used.

Different amounts (0, 1, 5, 10, 25 μl) of each solution (A, B or C) were added to each well. Subsequently, amounts of 25, 24, 20, 15 and 0 μl of 80% Dulbecco's MEM/20% FBS medium were added to each well to maintain a constant total volume. The growth behaviour and the amount of juvenile cells was checked after 96 hours. Therefore, a 50 μl sample was removed from each well. The cell number and the number of juvenile cells was determined by means of a Thoma chamber and divided by the initial cell amount of the respective cells. The cell number and number of juvenile cells in wells treated with 0 or 1 μl of solutions A, B or C were regarded as basic values and compared to that of wells treated with 5, 10 or 25 μl of solution A₅B or C, respectively. In comparison to the basic values, the addition of 5 μl solution A, B or C did not result in a detectable effect, since the values were within a 0.025 error range. The ratio of the cell number per initial cell number divided by the basic value obtained by addition of 10 and 25 μl of each solution are shown in table 1.

Table 1

The ratio of the number of juvenile cells per initial cell number divided by the basic value obtained by addition of 10 and 25 μl of each solution are shown in table 2.

Table 2

These values indicate that amounts of 10 and 25 μl of solution A and B have both a positive effect towards cell growth and cell reproduction, in that increased numbers of juvenile cells could be detected.

Claims

1. Use of a topical composition, comprising (i) a compound suppressing angiotensin II production or activity

(ii) at least one antioxidant; and (iii) at least one barrier compound; for the preparation of a medicament for the prevention and/or treatment of a skin ageing and disorders caused by skin ageing.

2. The use according to claim 1, wherein said topical composition is in the form of an ointment, cream, salve, lotion or gel.

3. The use according to claim 1, wherein said compound suppressing angiotensin II production or activity is selected from the group consisting of an angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers .

4. The use according to claim 3, wherein said angiotensin II receptor blockers are selected from the group consisting of valsartan, losartan, irbisartan, and angiotensin-converting enzyme from the group consisting of perindopril, ramipril, trandolapril.

5. The use according to claim 1, wherein said at least one antioxidant is a vitamin.

6. The use according to claim 5, wherein said vitamin is selected from the group consisting of vitamin A, vitamin C and vitamin E.

7. The use according to claim 1, wherein said least one barrier compound is a UV filter.

8. The use according to claim 7, wherein said UV filter is selected from the group consisting of UVA and UVB filters.

9. The use according to claim 1, wherein said compound suppressing angiotensin II production or activity is contained in an amount of 0.25 to 7.5 % by weight.

10. The use according to claim 1, wherein said at least one antioxidant is contained in an amount of 0.5 to 25 % by weight.

11. The use according to claim 1 , wherein said least one barrier compound is contained in an amount of 0.5 to 15 % by weight.

12. The use according to any of the preceding claims, wherein the skin disorder ageing of the skin is selected from the group consisting of wrinkles, skin lines, crevices, bumps, large pores, loss of skin elasticity, sagging, loss of skin firmness, loss of skin tightness, loss of skin recoil from deformation, discoloration, blotching, shallowness, hyper pigmented skin regions, keratoses, abnormal differentiation, hyperkeratinization, elastosis, collagen break- down.

13. The use according to any of the preceding claims, wherein the skin ageing is photo- ageing.