Issue 35 — December 2003

Issue 35
Category		Titel		Author
Guest Article		Dermocosmetics: Cosmetics and skin care from dermatological view — Current trends in dermocosmetics		Martina Kerscher

The number of active substances in cosmetical products has lately considerably increased. This applies in particular to active substances for the prevention and cosmetic treatment of skin ageing. Special importance is attached in this context to the active substances that are to protect the skin from harmful effects of UV radiation or repair of UV-related skin damage. Seldom these substances or their chemical example originate from nature. However, there are also recent developments in the field of elements and galenics of cosmetic products.

The average life expectancy has substantially increased in the last decades. As skin is the organ that reflects ageing in the most visible way, increased significance has been placed on dermocosmetics containing active substances against skin ageing. Moreover, a well-groomed appearance plays a more and more prominent role in today's society. Since cosmetics - in contrast to drugs - do not have to be authorized before launched to the market, a high degree of effectiveness and tolerability, i.e. a possibly high VW-index (VWI) should be a primary objective. This seems the more important if one considers that results of surveys reveal that every third consumer of cosmetics has already been faced with intolerability of a cosmetic product. Decisive extents of influence on the VWI are high-quality elements, optimised galenics as well as differentiated active substances.

Enlarged version

Recent basic elements

Besides water, fats and oils are the central raw materials for high-quality bases of dermocosmetic preparations. To the recent developments in the sector element substances belongs the application of fats and oils of vegetable origin. An example of this substance is for instance coco-mono-glycerid sulphate that is synthesized from coconut oil and glycerine [1] and has the properties of an anionic surfactant.

An additional group of partial synthetically modified vegetable raw materials are the protein-fatty acid condensates that equally belong to the anionic surfactants and are very well skin-tolerable. The non-ionic alkyl polyglycosides [2] composed of sugar and fatty alcohol distinguish themselves as well through excellent skin tolerability and a very low irritative effectiveness.

Current galenic systems

Modern skin care products have to come up to demanding standards in particular regarding effectiveness and tolerability. A differentiated galenic basis is therefore just as important as the incorporated active substances. One of the targets for the development of a topical formulation is the establishing of a qualified system for the release of these substances.

As vehicle for a controlled release of cosmetical active substances and the optimization of the availability of active substances in certain skin layers, nanodisperse systems as liposomes, nano-emulsions and lipidnanoparticles gain more and more in importance. Thus, in some dermocosmetics uncharged liposomes are applied the most important effect of which can be seen in the increased hydratation of skin [3]. Moreover, liposomes allow a fixing of active substances in the upper skin layers. A washing out and continuing penetration are hereby impeded. The more difficult washing out raises for example the waterproofness of UV-filters.

In many cases even better suited than liposomes are nano-emulsions. Similar to liposomes they enhance the penetration of cosmetic active substances and intensify thus their concentration in skin [3]. Moreover, nano-emulsions gain more and more in importance because of their cosmetic intrinsic activity. By infiltrating of qualified lipids by means of nano-emulsions, the barrier function can equally be improved. Beyond it, lipidnanoparticles have been patented under the names Lipopearls® and Nanopearls® [4]. They seem to allow an improved stability of chemically unstable active substance as well as a controlled release of active substances, enhanced hydratation and a good control effect by film formation.

Many dermocosmetics consist of two or more substances that are not miscible with each other and only reach a sufficient stability by certain additives. Often such formulations are stabilized with classical emulsifiers of the type of ionic or non-ionic surfactants. These low-molecular, amphiphile substances, however, may cause incompatibilities as skin irritations over and over again. Systems that are stabilized by classical emulsifiers with polymers or solid matters serve as alternative systems.

Intrinsic und extrinsic skin ageing

Skin ageing is understood today as a consequence of a combination of chronological, intrinisic skin ageing and extrinsic skin ageing determined by exogenous noxae. In this context it is proceeded from the assumption that the intrinsic or chronological skin-ageing is a consequence of genetical processes leading to a decreasing functionality of the skin. The intrinsic skin ageing entails fine wrinkles in skin. Intrinsic ageing skin shows additionally a loss of elasticity.

The extrinsic skin ageing is determined by exogenous effects in particular UV-radiation. Also smoking is considered as noxa. The formation of reactive free radicals, also called reactive oxygen species, is considered to be an essential mechanism leading to extrinsic skin ageing [5]. These extremely reactive substances entail the oxidation of most varying cell elements such as DNA, proteins and membrane lipids [5, 6].

Furthermore, the expression of metalloproteinases is induced by UVA-radiation [7]. This leads to a reduction of collagenic and elastic fibers. Further, a deposition of elastotic material comes about as well as an increased development of glycosaminoglycanes. Clinically extrinsic skin ageing typically occurs at skin areas that are exposed to environmental influences. Here it superimposes the symptoms of intrinsic skin ageing. It is characterized by coarse wrinkles and elastosis.

If one considers the complex mechanisms that may lead to ageing symptoms of skin it is comprehensible that there is a large number of possible attempts in order to influence the ageing of skin. This is why in the following the latest scientifically investigated and at present frequently used active substances as well as some innovations are dealt with.

Vitamin A and its derivatives

Vitamin A and its derivatives belong to the longest applied anti-ageing substances. Used are both vitamin A (retinol) and vitamin-A-acid (tretinoine) and the aldehyde retinal (retinaldehyde). All derivatives of vitamin A exercise their specific effect on the nuclear receptors and have a complex impact on the skin tissue via their effects on the gene-expression. By applying tretinoine, a very good effect on the typical symptoms of skin ageing with epidermal and dermal effects could be proven [8]. Accordingly, the activity of collagen and elastine-decomposing collagenase are impeded by the vitamin-A-acid. The synthesis of new collagen is stimulated and damaged collagen- (type I and III) and elastine fibers are re-organized [9]. As drug available on prescription only, tretinoine may no longer be used for cosmetic preparations.

Similar as for tretinoine, recent scientific investigations have also shown a positive effect on ageing symptoms of skin [10] for retinol. Thus, by using retinol both with intrinsic and extrinsic skin ageing, a reduction of the mRNA-expression of the collagenase (MMP-I) as well as a stimulation of the collagen-synthesis [11] is effected. In contrast to vitamin-A-acid, retinol is also allowed for applications in cosmetic products. It is employed as active substance in numerous dermocosmetics and very well tolerated.

As for tretinoine and retinol a stimulation of the collagen synthesis and a reduction of the collagenase activity could also be shown for retinaldehyde. Partly, a restoration of damaged collagen fibers with restructuration of the connecting tissue has occurred [12]. In comparison with tretinoine, retinaldehyde has partly been better tolerated [13].

Oestrogens and phytooestrogens

In the frame of the menopause, the female oestrogen levels distinctly decrease. This leads among others to a weaker influence of oestrogens at the cells of the skin. Sinking oestrogen levels are therefore considered as a factor for intrinsic skin ageing with post-menopausal women. In various studies, a positive effect of topically applied oestrogens on elasticity and wrinkle formation of skin could be demonstrated. Also a stimulation of the collagen metabolism combined with a rise of the collage type III has been shown [14]. The exact scientific evaluation of effects of oestrogens in the context of skin ageing has nevertheless not been completed.

In contrast to oestrogens that are available on prescription only, the so-called phytooestrogens are applied in cosmetical products. This implies different substances of vegetable origin such as isoflavone, cumestane and lignane, as for example in soy and soy products, green tea and ginseng [15]. Scientific investigations regarding the effect of these substances on skin ageing is however not yet terminated, however positive effects on phytooestrogen-containing creams on skin ageing become apparent.

Antioxidant vitamins C and E

The significance of reactive oxygen species (ROS) in connection with skin-ageing has especially in the last years lead to an intensive search for active substances able to eliminate the harmful effects of ROS, thus protecting the tissues from oxidative damage. Substances possessing these properties are summarizingly called antioxidants. This is a very heterogeneous group of active substances that possess further effects on the skin tissue besides their antioxidative properties. In part, these substances are bound to certain cell compartments. Some antioxidants are oxidized and metabolized in contact with ROS, a part however, by oxidation of an additional molecule regenerated. Antioxidants are able to increase the dose, which is required to generate an immediate pigmentation [16].

Marked antioxidative properties possesses for example vitamin C (ascorbic acid). This hydrophilic substance is used today for different anti-aging products. Besides its antioxidative properties ascorbic acid acts on the differentiation of skin. Thus, the substance is involved in the hydroxylation of proline in the area of the protein cord of the collagen molecule. A supply of ascorbic acid entails a stimulation of the connecting tissue metabolism with increased mRNA expression of collagen-synthesizing enzymes and thus also the regeneration of age-related connecting tissue damages. In addition, an increase of the collagenase-inhibitor-protein comes about through which the collagen and elastine decomposing collagenase is impeded [17].

Besides the complex effect on the connective tissue metabolism and the effects related on skin-ageing, to vitamin C is also attributed a differentiation-enhancing effect in the sector of the epidermal barrier. Thus it could be shown that the differentiation degree of ceramides in the area of the epidermal barrier in reconstructed skin increases by adding of ascorbic acid [24].
Vitamin E or alpha-tocopherol belong to the lipophile antioxidants. Therefore, it can is able to catch free radicals especially in the lipophile milieu of biological systems for example at cell membranes. By topical applications of vitamin E, an additional protection by reduction of UVA-induced oxidative stress can be caused. A significant decrease of peroxidized phospholipids under the application of vitamin E could be shown [19]. Further, vitamin E also impedes the gene expression of the collagenase [20] by an inhibition of the proteinkinase C activity. Additional investigations have shown that vitamin E is able to protect from a ROS-related inhibition of the collagen biosynthesis and a ROS-caused stimulation of the glycosaminogklycansynthesis [11].

Additional antioxidants

Further substances with anti-oxidative properties are coenzyme Q 10 and flavonoids. An analysis has shown a reduction of the oxidative stress, a decrease of the collagenase activity by applying coenzyme Q 10 [21].

Flavonoids are a large group of polyphenolic compounds that have been found in plants and correspondingly in the most varied foodstuffs of vegetable origin [22]. Flavanoles, flavanones, antho-cyanidines, flavones and flavonoles belong to the flavonoids. Important examples are the polyphenoles with epica-techine, epigallocatechine and epicatechnin-3-gallat as the most significant representatives. Lately, a photo-protective effect could be proven in vivo for green tea phenols. When applying of green tea phenols before UV exposition, a significantly lower number of "sunburn cells" showed, a considerably lower decrease of Langerhans-cells as well as distinctly less DNS-damages than with previous application of these substances [23].

Skin protection substance ectoine

Ectoine, a tetrahydropyrimi-dincarbonacid belongs to the so-called compatible solutes. This term comprises a group of chemically differing substances that are naturally found with bacteriae. Ectoines are amphoteric water-binding substances that protect bacteriae at high exterior temperatures and low atmospheric humidity from water loss and heat. They stabilize proteins, nucleic acids and membranes. These properties lead to a testing of ectoine in recent times as skin protection substance. In first in-vitro analyses, protecting effects against UV radiation could be demonstrated for this substance. Thus, the UVB-induced decrease of Langerhans-cells when applying of ectoine before ray treatment is clearly lower. Furthermore, the number of the "sunburn cells" in vitro by application of ectoine is significantly reduced. Moreover, ectoine entails a swifter formation of heat-shock proteins. Additionally, a hydratizing effect could be shown in vivo [25].

DNS repair enzymes

Besides the protection of skin from exterior affecting environmental noxae as UV radiation and the oxidative stress connected herewith, the repair of occurring DNS damages by so-called DNS repair enzymes represent a relatively new trend. Representatives of this substance group are the photolyasis, the T4N5-endonucleasis or also the optitelomerasis.

When applying of a liposomal photolyase emulsion a partial disintegration of UVB-induced thymidindimers comes about. Photolyasis binds the DNS and disintegrates partially the dimers by activating of electromagnetic radiation in the spectral area between 300 and 500 nanometers. In a corresponding investigation by applying of photolyasis, a reduction of thymindindimere by 40 to 45 percent could be shown [26].

The application of liposomal T4N5-endonucleasis represents a further approach for the repair of UV-induced pyrimi-dindimers. Thus the rate of newly developing skin carcinomae after application of a liposomal endonucleases-lotion could be significantly reduced with patients suffering from xeroderma pigmentosum [27]. To what extent such a product is useful for the improvement of UV-induced long-term damage without the presence of enzyme defects appearing with Xeroderma pigmentosum cannot be finally evaluated at present.

Literature

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This article by Prof. Dr. med. Martina Kerscher and Dr. med. Tilmann Reuther of the course of studies Cosmetics and Personal Hygiene at the department Chemistry of Hamburg University, Martin Luther-King Platz 6, D-20146 Hamburg was published in DermoTopics 1 (2002).

Professor Kerscher held a lecture referring to this subject on the occasion of the symposium "Effects of Dermocosmetics" on 17 October 2001 organized by the Gesellschaft für Dermopharmazie at the Fritz-Henkel-Haus in Düsseldorf.

Author

Martina Kerscher



Dermatologist Professor Dr. med. Martina Kerscher is regarded as advocate of scientifically based dermocosmetics. She contributes her expertise in her work for the Gesellschaft für Dermopharmazie.