EP1443895A2

EP1443895A2 - Utilization of sterols and their derivatives in cosmetic and dermatological preparations for uva protection

Info

Publication number: EP1443895A2
Application number: EP02796498A
Authority: EP
Inventors: Susanne Grether-Beck
Original assignee: Skinlab GmbH
Current assignee: Skinlab GmbH
Priority date: 2001-11-12
Filing date: 2002-11-11
Publication date: 2004-08-11
Also published as: WO2003041675A2; DE10155200A1; WO2003041675A3

Abstract

The invention relates to the utilization of cholesterol, lanosterol, phytosterols and different sterols of natural and artificial origin in accordance with formula (I) for the protection of the skin against the harmful effects of UVA radiation. The above-mentioned substances are excellent active ingredients for the production of sunscreen agents. Particularly effective are cholesterol and lanosterol, in addition to different phytosterols such as stigmasterol.

Description

Use of sterols and their derivatives in cosmetic and dermatological preparations for the purpose of UVA protection

Exposing human skin to prolonged exposure to the sun can lead to light or photodermatosis in a wide variety of forms. Examples include sunburn, light-induced skin aging and skin cancer. The photodermatosis-triggering effect of sunlight is attributed, among other things, to the UVA radiation contained in the sunlight spectrum, which is also emitted by artificial radiation sources, for example solariums.

To protect against UV radiation, customary sunscreens contain substances to form a protective layer on the skin, which absorb and / or reflect the radiation in the range from 280 to 400 nanometers. Such inorganic photoprotective substances are for example oxides such as titanium dioxide in the form of its natural crystal forms rutile, brookite or anatase or zinc oxide, organic filters are for example cinnamic acid derivatives or derivatives of dibenzoyl methane.

In addition to pure absorber molecules, some of the previously known sunscreens also contain biologically active additives such as antioxidants, DNA repair enzymes or anti-inflammatories. Finally, sunscreen agents containing lanolin are also known. However, the lanolin containing cholesterol is used in these formulations only as an inert vehicle or galenic component, of which a protective effect has not become known and which, according to the knowledge of the experts consequently could only serve as a carrier for the solution or dispersion of active ingredients.

Particularly in view of the recently increasing intensity of the UV component in the spectrum of sunlight, it is desirable to provide the most comprehensive possible skin protection in addition to the above-mentioned radiation absorbers to be able to access substances which have a different effect and the known physical effects through a therapeutically novel physiological effect.

The object of the invention is therefore to improve the skin protection against the consequences of harmful UVA radiation in a physiological way.

In the broadest sense, the inventors have set themselves the task of effectively increasing the protection of the skin against the consequential damage caused by excessive UVA exposure beyond the abovementioned and already known possibilities, and of providing agents which protect the skin on a new physiologically unknown hitherto Complement the path in a valuable way.

To solve this problem, it is proposed to use one or more compounds of the general formula I

in which one of the two bonds identified by a and b and shown in dashed lines represents a single bond and the other represents a double bond, and the bond denoted by c can be both a double bond and a single bond,

Ri represents a hydrogen atom, a straight-chain or branched Ci to C ₄ alkyl radical or together with R ₂ a double bond,

R _{2 represents} a hydrogen atom or together with Ri a double bond and

R ₃ , R ₄ and R5 can independently of one another be a hydrogen atom or a methyl group,

and compounds containing the formula I or substances which increase the cholesterol content of human skin for the production of cosmetic or dermatological preparations for protecting the skin from the harmful effects of UVA radiation.

Formula I does not take into account the actual steric conditions.

The above substances are excellent as sunscreens and can therefore be used to protect the skin from the harmful effects of UVA radiation.

In addition to the abovementioned radicals, the alkyl radicals for R 1 are propyl, isopropyl, n-butyl, isobutyl or tert. Butyl residue in question.

The present invention therefore relates to the use of compounds of the general formula I and of compounds of the formula I or substances which increase the cholesterol content of human skin for the production of cosmetic or dermatological preparations for protecting the Skin before UVA radiation and for the prevention and treatment of inflammation conditions which are caused or caused by increased UVA radiation.

According to the invention, it has been possible to intervene effectively with the proposed agents in the inflammatory process, which is a consequence of excessive UVA radiation exposure to the skin. Another object of the invention is consequently the use of compounds of the general formula I, and of compounds of the formula I or substances which increase the cholesterol content of human skin for the prevention and treatment of inflammatory conditions which are caused or caused by increased UVA radiation.

The simplest representative of the compounds according to formula I is cholesterol (Ri to R5 = hydrogen, a = double bond, c = single bond).

Cholesterol (cholesterol) belongs to the family of lipids and occurs in almost all animal cells. Fish oil or wool fat are the best known representatives of the cholesterol-containing substances.

With the molecular formula C ₂₇ H ₄ 6θ and a molecular weight of 386.64 g / mol, cholesterol crystallizes in the form of colorless platelets which, under normal conditions, have a density of 1.052 g / cm ³ and a melting point of 148.5 ° C. Its boiling point is 360 ° C. As a lipid, cholesterol is practically insoluble in water. However, cholesterol is soluble in lower aliphatic alcohols such as ethanol and is readily soluble in nonpolar solvents such as benzene or ether.

Further representatives of the formula I are in particular lanosterol (Ri forms a double bond with R ₂ , b = double bond C = single bond, and the radicals R3, R ₄ and R5 are each methyl groups) and plant sterols (phytosterols), the most important of these Compounds for Ri have an alkyl substituent, in particular a methyl or ethyl group.

The methyl- or ethyl-substituted derivatives are the only ones that contain carbon atoms that do not originate from the known acetate-mevalonate pathway, and they are just as little present in the first sterol intermediates of plants (cycloartenol) as in such intermediates of animals or fungi [Nes and McKean, 1977)].

These connections include a .:

β-sitosterol (Ri = ethyl, R ₂ , R ₃ , R ₄ and R ₅ = H, a = double bond, c = single bond), which is made from soybeans, wheat germ, corn, cottonseed, rice germs, dandelion roots, potatoes or the bark of Pine, such as Peruvian pine and other vegetable sources, can be obtained;

Campesterol (Ri = methyl, R ₂ , R ₃ , R ₄ and R ₅ = H, a = double bond, c = single bond),

Stigmasterol, (Ri = ethyl, R ₂ , R ₃ , R ₄ and R ₅ = H, a and c are double bonds), which can be obtained from calabar beans (fruits of Physostig a venenosum) and soybeans. It serves as the starting material for steroid synthesis; such as

Lanosterol (Ri forms a double bond with R ₂ , b = double bond, c = single bond and the residues R ₃ , R ₄ and R5 are methyl groups), which is mainly obtained from sheep's wool. Lanosterol is a precursor to cholesterol synthesis.

Plant sterols are found in the fat-soluble fractions of plants and chemically correspond to cholesterol. They inhibit cholesterol absorption in the small intestine and are used, for example, in low-fat spreads, which are intended for this purpose are to lower total cholesterol and LDL cholesterol (Nigon et al. 2001). Plant sterols of edible oils and fatty acids from sunflower seed oil consist of 50% sitosterol esters, 25% campesterol esters, and 20% stigmasterol esters and other compounds. As one of the main sources of plant sterols, soybeans (Glycine max) were examined for their sterol composition. The following results were obtained for total sterols:

61% sitosterol, 17% stigmasterol, 5% campesterol in the seedlings and 23% sitosterol, 3% stigmasterol and 9% campesterol in the seed material (Marshall et al. 2001). This distribution of plant sterols is fairly widespread and even in Arabidopsis sitosterol is the predominant plant sterol (48%) followed by campesterol 20% (Diener et al. 2000). The most important plant sterols contain an alkyl substitution at the carbon atom 24, corresponding to R ¹ in the general formula I, which is missing from cholesterol.

The invention is based on the newly found activity of the compounds I, in particular cholesterol, against human keratinocytes.

It is known that UVA radiation triggers the expression of certain genes in the keratinocytes [Proc.Natl. Acad.Sci 93, p.14586-14591, Biol. Che 378 (1973) p. 1231-1236]. The resulting gene products, along with other influencing factors, are largely responsible for the undesirable occurrence of light dermatoses, such as polymorphic light dermatosis, and for the occurrence of degenerative skin changes. Examples of this are e.g. Mallorca acne, light-induced skin aging and skin cancer, especially malignant melanoma.

Expression of the inflammation marker intercellular adhesion molecule 1 (hereinafter: ICAM-1) is induced, for example, by increased radiation exposure by UVA. It has now been found that sterols of the general formula I, in particular cholesterol or lanosterol, and substances or compounds containing such sterols, which increase the cholesterol content of the skin, are surprisingly potent photoprotective active ingredients which essentially reduce the human skin against undesirable UVA-induced damage protect more effectively than that of protectors in preparations for the skin is known to date. Experimental investigations confirmed this finding and proved that the above-mentioned effect can be found not only in the basic skeleton of cholesterol, but also in the natural and possibly also artificial derivatives defined by formula I and listed above.

Preferred for Ri are hydrogen, methyl and ethyl, and a double bond formed jointly by the radicals R ¹ and R ² . Particularly preferred compounds of the formula I are cholesterol, lanosterol, β-sitosterol, campesterol and stigmasterol.

Not only the compounds of the general formula I themselves can be used as active according to the invention, but also a) those substances which contain compounds of the general formula I, in particular cholesterol, in a concentration which is suitable for the absorption of the compounds I through the skin ensures sufficient effect according to the invention, and b) compounds which pharmacologically enable the increase in cholesterol in human skin.

Group a) includes, for example, the cholesterol-containing wool wax alcohol lanolin.

Group b) includes, for example, docosanoic acid (or behenic acid), which occurs in mustard oil, liver oil, peanut oil and rapeseed oil, cafestol and Kahweol, diterpenes that can be isolated from coffee beans, lauric acid, myristic acid, palmitic acid and unsaturated trans fatty acids. Just as cholesterol-lowering agents such as statins (lovastatin, simvastatin, atorvatatin) can lower the cholesterol level in the body, such substances are able to increase the cholesterol concentration in the skin tissue via certain metabolic processes. The cholesterol content of human cells is 0.32% on average, whereby cholesterol is found, for example, in the brain, spinal cord, in the adrenal glands or in the blood. It is also present in large quantities in the gallstones from which it was isolated for the first time. Cholesterol is either free or is esterified with higher fatty acids. It is obtained by extracting cholesterol-containing substances, for example from powdered gallstones. Technically, cholesterol is obtained from wool fat or animal spinal cord, for example.

Cholesterol is biosynthesized starting from acetyl-CoA via mevalonic acid, squalene and lanosterol mainly in the liver but also in the minor cortex (Römpps Chemie Lexikon, 9th edition, 1995).

It is known to use cholesterol as an emulsifier for cosmetic and pharmaceutical preparations, textile goods, leather care products, hair restorer and as a starting material for vitamin D synthesis.

In particular, it is known that cholesterol is part of the cell membrane, although its mode of action and importance in this regard have not yet been fully elucidated. However, it has been demonstrated that an increase in the cholesterol content leads to an increase in the viscosity of the cell membrane and thus to a decrease in its permeability to water molecules. In this context, the orientation of the molecules at the lipid / water phase boundary obviously also plays a role. The change in membrane permeable speed can also influence the activity of surface-active enzymes or cell membrane-associated receptors. In the skin, cholesterol is an important component of the epidermal permeability barrier. The divisible keratinocytes of the skin in the stratum basale contain only small amounts of lipids, which mainly belong to the group of phospholipids, cholesterols and triglycerides. When the keratinocytes are divided and differentiated, their lipid content increases due to the synthesis of fatty acids, phospholipids, glucosylceramides and cholesterol. The lipids accumulate into lamellar granules, which fuse with the cell membrane when the keratinocytes of the stratum granulosum are converted into corneocytes of the stratum corneum. The contents of the granules, which consist of glycoproteins, glycolipids, phospholipids, free sterols and various hydrolases, pour into the intercellular space.

With regard to skin-related use, it is only known to use cholesterol or cholesterol-containing substances such as lanolin as an emulsifier in cosmetic or dermatological preparations.

DE-A 43 28 828, for example, discloses a hand disinfectant containing cholesterol, the cholesterol having an effect such that excessive skin drainage caused by frequent disinfection of the hands is avoided.

From [Arch. Dermatol. Res. 123 (1987) pp.1535-1538] it is also known that the use of cholesterol-lowering agents such as fluvastatin and lovastatin leads to hyperplasia with peeling and desquamation of the epidermis. The cholesterol-lowering agents inhibit HMG-CoA reductase as the key enzyme in cholesterol synthesis.

Clofazamine-induced ichthiosis has also been identified as a side effect of lepratherapy, which is also a Represents the inhibition of cholesterol synthesis [J. of Der atol., Venerol and Leprology 60 (1994), pp. 130-132].

It is also known to reduce the side effects on the skin caused by typical cholesterol-lowering drugs such as e.g. Lovastatin are caused by topical cholesterol treatment [J. Invest. Dermatol. 96 (1991), pp. 201 to 209 and 98 (1992), pp. 209 to 219].

It is also described that the ability of the skin to repair in older people is impaired due to a decreasing rate of synthesis [J. Clin. Invest. 95 (1995) pp. 2281-2290] and that lipid preparations with a high cholesterol content increase the skin's ability to repair in older people [J. At the. Acad. Dermatol. 37 (1997) pp. 403-408].

It is also described that the HMG-CoA reductase inhibitor lovastatin increases the phototoxicity of UVA radiation in cultured human keratinocytes [Bioche. j. 310 (1995) pp. 305-309].

It is also known from WO 00/45786 that the thickness of the stratum corneum can be increased by means of the sulfuric acid ester of cholesterol, which acts as a protease inhibitor, and a so-called light callus, a natural obstacle to UVB rays, can be generated in this way. However, this does not provide protection against UVA radiation. Cholesterol sulfate does not accumulate in the cell membrane and is therefore fundamentally unable to inhibit the expression of UVA-induced inflammation markers in the keratocytes.

The application of the substances according to the invention to the skin or the epidermis should depend on the respective expediency and is arbitrary in this sense, as long as only the interaction between the active substance according to the invention and the keratinocytes is ensured and the active substance is not isolated from the keratinocytes by the selected galenics becomes. In general, the active compounds according to the invention can be galenically processed in a customary manner using suitable skin-compatible and pharmaceutically acceptable additives. Such additives are, for example, emulsifiers, solvents, thickeners, fillers, stabilizers, preservatives, antioxidants or fragrances. If necessary, bioavailability can be improved with surface-active agents, such as polyoxyethylene sorbitan esters or salts of bile acid.

However, other active ingredients can also be added. These include, for example, vitamins, anti-inflammatories, the known inorganic or organic UVA filters mentioned above to further increase the protection factor, and antibacterial, fungistatic or fungicidal agents.

For incorporating insoluble substances, e.g. of the inorganic oxides mentioned, if desired, dispersants, such as e.g. Polyacrylates, lignin, tannates or their derivatives added. Colloidal silicon oxide or laponite can be used as the thickening agent. Hydrogels can be mixed with hydrophilic organic solvents, e.g. Prepare glycerin, glycol or with aliphatic alcohols.

Furthermore, it is also possible within the scope of the invention to use the active compounds according to the invention, for example cholesterol, in the form of microsomes or liposomes containing active compounds, and in repair systems encapsulated in microsomal or liposomes and so-called active agents, if appropriate in addition to other auxiliaries and other active compounds.

The active compounds according to the invention can, according to the invention, be processed into preparation forms suitable for use on human skin. Such forms of preparation are, for example, tinctures, hydrogels, O / W emulsions, W / O emulsions, lotions, creams, ointments or sprays. In the case of the compounds of the general formula I, the concentration suitably depends on the activity, since no toxic or skin-irritating factors of the compounds I are known which require the concentration to be limited. For cholesterol, for example, the most favorable concentration is in the range from 0.5 to 10% by weight.

The preparations contain the compounds of general formula I in a concentration of 0.1 to 20% by weight, based on the weight of the carrier material used. Concentrations of 2 to 10% by weight are preferred.

Cholesterol can, for example, be in a tincture consisting of propylene glycol and ethanol (in a volume ratio of 7: 3) and cholesterol in a concentration of about 25 grams per liter, e.g. with a brush, to be applied to the skin.

In another embodiment of the invention, a cholesterol-containing substance consisting of cholesterol, ceramide, palmitate and oleate in a weight ratio of 3: 1: 1: 1 is dissolved in an alcohol mixture of propylene glycol and n-propanol in a volume ratio of 7: 3, the The weight fraction of the cholesterol-containing substance is 3%, based on the total mass.

In a further exemplary embodiment, a common petrolatum-based cream was mixed with a lanolin-alcohol mixture with a mixing ratio of 1.5 g lanolin to 100 ml ethanol.

In a further embodiment, 1 ml of lanolin was added to 100 ml of a lotion. Foπαulierungsbeispiele:

1. Sunscreen milk based on cholesterol:

2. Cholesterol-based sunscreen:

3.Lanosterol-based sun protection cream:

4.Sunosterol-based sunscreen:

Fat bases: paraffin oil, amphiphilic substances such as long-chain fatty alcohols, isopropyl palmitic acid

Polyhydric alcohols: glycerin, propanediol, sorbitol

Solid thickeners: starch, dextrin, dextran, pectin, acacia, agar, methyl cellulose, gelatin / collagen, polyvinyl alcohol, carbopol, silica gel, diatomaceous earth.

Preservatives: 4-hydroxybenzoic acid methyl or propyl ester

Antioxidants: Vitamin E, Vitamin C and their derivatives.

perfume oil

UV absorber: derivatives of benzophenone; 4-aminobenzoic acid, salicylic acid ester, 4-methoxycinnamic acid ester, 3-benzylidene camphor derivatives, titanium dioxide

Using conventional manufacturing processes for creams and sun milk preparations, the auxiliary substances are mixed and emulsified in suitable vessels according to the examples mentioned above and, if appropriate, filled into tubes, bottles or cans. Experimental results:

FIG. 1 shows the time-resolved expression of ICAM-1 in primary human keratinocytes in relation to the expression of β-actin after continuous UVA irradiation for 10 to 15 minutes with an energy density of 30 J / cm ² . The investigated keratinocytes were thus exposed to a radiation dose which essentially corresponds to that of sunlight around noon on a summer day in a latitude of 30-35 ° N for a period of 1 to 2 hours.

It can be seen that the ICAM-1 content increases three to four times after just half an hour. This influence of UVA radiation on the gene expression of the keratinocytes, shown here by way of example for ICAM-1, corresponds to the initial change that can be observed in the development of light dermatoses such as polymorphic light dermatosis and in the development of light aging and skin cancer in human skin ,

Figure: 2

shows the β-actin-related expression of ICAM-1 in primary human keratinocytes, which were preincubated in cholesterol before a corresponding UVA radiation. The addition of cholesterol showed no increase in ICAM-1 expression even after half an hour. With longer waiting times there was even a decrease in ICAM-1 expression. Since UVA-induced gene expression, here using the example of ICAM-1 shows that it is a measure of the probability of the occurrence of polymorphic light dermatoses, skin cancer or light-induced skin aging, it could be demonstrated for the first time that preincubation of primary normal human keratinocytes with cholesterol leads to a complete inhibition of UVA-induced gene expression. It follows that cholesterol has a previously unknown photoprotective effect.

In accordance with the above model, in addition to cholesterol, the UVA-induced ICAM-1 expression on primary human keratinocytes (FIGS. 3 to 10) or on human skin equivalents (FIGS. 11-21) was analyzed after preincubation with sitosterol, campesterol, stigmasterol or lanosterol.

FIG. 3 shows that the value of the ICAM imRNA undergoes an increase after UVA irradiation of primary human keratinocytes with a dose of 30 J / cm ² UVA.

FIG. 4 shows that the value of the ICAM imRNA after incubation of primary human keratinocytes with cholesterol in a concentration of 30 μM is not significantly increased.

FIG. 5 shows that ICAM-lmRNA expression is inhibited after incubation of primary human keratinocytes with cholesterol in a concentration of 30 μM and subsequent UVA irradiation with a dose of 30 J / cm ² UVA.

FIG. 6 shows that the value of the ICAM imRNA experiences a slight increase after incubation of primary human keratinocytes with sitosterol in a concentration of 30 μM. FIG. 7 shows that UVA-induced ICAM-lmRNA expression is inhibited after preincubation with sitosterol in a concentration of 30 μM and subsequent UVA irradiation with a dose of 30 J / cm ² UVA.

FIG. 8 shows that the value of the ICAM imRNA experiences a slight increase after incubation of primary human keratinocytes with campesterol in a concentration of 30 μM.

Figures 9 to 20:

In order to further investigate the concept of photoprotection by means of sterol treatment, the induction of inflammation-promoting molecules was e.g. ICAM-1 also tested on human skin equivalents (see the following Figures 9 to 20). This concept makes sense because a three-dimensional skin model comes particularly close to human tissue because it includes the basal lamina and the epidermis with the stratum corneum. This skin model is recognized as a test model for cosmetic and pharmaceutical products (Noll et al. 1999).

FIG. 9 shows that ICAM-lmRNA expression is inhibited after preincubation of keratinocytes with campesterol in a concentration of 30 μM and subsequent UVA irradiation with a dosage of 30 J / cm ² UVA.

FIG. 10 shows that the value of the ICAM imRNA increases after UVA irradiation of human skin equivalents with a dosage of 10 J / cm ² UVA 1.

Figure: 11 shows that after treatment of human skin equivalents with cholesterol in a dosage of 30 µM, the value of ICAM-1 experiences a slight increase by a factor of 1.4 after 16 hours. Figure: 12 shows that UVA-induced ICAM-1 expression in skin equivalents was prevented by a 24-hour pre-incubation with a cholesterol dosage of 30 M.

Figure: 13

Preincubation with ß-sitosterol in a dose of 30 µM results in a slightly increased ICAM-1 induction up to a factor of 1.4 after 16 hours.

Figure: 14

UVA-induced ICAM-1 expression in skin equivalents was prevented by a 24 hour pre-incubation with ß-sitosterol at a dose of 30 µM.

Figure: 15

Treatment of skin equivalents with campesterol in a dosage of 30 μM results in a slightly increased ICAM-1 induction up to a factor of 1.4 after 16 hours.

Figure: 16

UVA-induced ICAM-1 expression in skin equivalents was prevented by a 24-hour pre-incubation with campesterol at a dose of 30 μM.

Figure: 17th

Treatment of skin equivalents with stigmasterol in a dosage of 30 µM results in a slightly increased ICAM-1 induction up to a factor of 1.4 after 16 hours.

Figure: 18th

UVA-induced ICAM-1 expression in skin equivalents was prevented by preincubation with stigmasterol at a dose of 30 μM for 24 hours.

Figure: 19th

Treatment of skin equivalents with lanosterol in a dose of 30 µM results in a slightly increased ICAM-1 induction up to a factor of 1.4 after 16 hours. Figure: 20

UVA-induced ICAM-1 expression in skin equivalents was prevented by a 24 hour pre-incubation with lanosterol with a dosage of 30 μM.

Claims

claims

Use of sterol derivatives of the general formula I,

in which one of the two bonds marked with a and b and shown in dashed lines represents a single bond and the other a double bond, and the bond denoted by c can be both a double bond and a single bond,

R _{2 represents} a hydrogen atom or together with Ri a double bond and

R3 R ₄ and R5 can independently of one another be a hydrogen atom or a methyl group, and of compounds of the formula I and / or substances which increase the cholesterol content of human skin for the production of cosmetic or dermatological preparations for protecting against or for treating skin damage which are brought about by UV radiation.

2. Use according to claim 1, wherein Ri is a hydrogen atom, a methyl or ethyl radical or together with R∑ forms a double bond, R ^{2 represents} a hydrogen atom or together with R ^{1 forms} a double bond and the radicals R ₃ , R ₄ and R are hydrogen or represent a methyl group.

3. Use according to claim 1 or 2, wherein the sterol derivative is cholesterol.

4. Use according to claim 1 or 2, wherein the sterol derivative is lanosterol.

5. Use according to claim 1 and 2, wherein the cholesterol-containing substance is lanolin.

6. Use according to claim 1 and 2, wherein the sterol derivative is a plant sterol.

7. Use according to claim 6, wherein the plant sterol is β-sitosterol, camposterol, stigmasterol or lanosterol.

8. Use according to claim 1 to 7, wherein the skin damage is light dermatoses, in particular polymorphic light dermatoses, light-induced skin aging or skin cancer.

9. Use according to claim 1 to 8, wherein the cosmetic or dermatological composition is one of the usual Auxiliary tincture, lotion, o / w emulsion, w / o emulsion, cream, ointment or a hydrogel or spray.

10. Use according to claim 1 to 9, wherein the cosmetic or dermatological composition is a sunscreen preparation containing conventional UVA-absorbing active ingredients.

11. Use according to claim 1 to 10, wherein the cosmetic or dermatological preparation is an ointment, cream or lotion which has active ingredient-containing flexible liposomes.

12. Use according to claim 1 to 11, wherein the cosmetic or dermatological preparation is an ointment, cream or lotion which contains the microsomally encapsulated active ingredient.

13, use of sterol derivatives of the formula I,

in which one of the two bonds marked with a and b and shown in dashed lines represents a single bond and the another represents a double bond, and the bond denoted by c can be both a double bond and a single bond,

R _{2 represents} a hydrogen atom or together with Ri a double bond and

as well as compounds of the formula I and / or substances which increase the cholesterol content of the human skin according to the preceding claims 2 to 12, for protection against or for the treatment of skin damage caused by UV radiation.