EP1844146A2 - Cosmetic or pharmaceutical preparations containing nucleic acids having sequences suited for forming stem-loop secondary structures - Google Patents

Abstract

The invention relates to: cosmetic or pharmaceutical preparations for preventing and/or treating epithelium that contain nucleic acids, which have sequences suited for forming stem-loop secondary structures; the use of nucleic acids of this type, which have sequences suited for forming stem-loop secondary structures, for preventing and/or treating epithelium, and; fabric softeners, hand detergents, body and hair care products, hair coloring agents or hand dishwashing detergents containing these nucleic acids that have sequences suited for forming stem-loop secondary structures.

Description

Cosmetic or pharmaceutical preparations containing nucleic acids comprising sequences suitable for the formation of stem-loop secondary structures

Description:

The present invention relates to cosmetic or pharmaceutical preparations for the prophylaxis and / or treatment of epithelial cover tissue containing nucleic acids comprising sequences suitable for the formation of stem-loop secondary structures; the use of such nucleic acids which comprise sequences suitable for the formation of stem-loop secondary structures, for the prophylaxis and / or treatment of epithelial covering tissue and fabric softeners, hand washing compositions, body and hair care preparations, hair dyes or hand dishwashing detergents containing such nucleic acids which are used to form stem loop secondary structures comprise suitable sequences.

Inflammations of the skin organ are widespread diseases that can be triggered both endogenously and exogenously. For treatment, steroid-based therapeutics are usually administered topically or systemically. This class of drugs, in addition to their efficacy, also has a number of undesirable side effects (e.g., skin atrophy, Cushing syndrome). An alternative principle for the treatment of inflammation of the skin is therefore desirable.

One such alternative treatment principle is the use of antiinflammatory nucleic acids.

The historical background of the immunostimulatory activity of DNA dates back to the 19th century. In 1893, the New York surgeon William Coley reported that bacterial lysates (streptococcal lysates, later called "Coley's tox / πe") - injected intratumorally - contributed to the regression of tumors Induce sarcoma patients. The importance of Coley's historical discovery that a specific antitumoral immune response is enhanced by imitation of a bacterial infection was not recognized until 100 years later, when the mechanism of the antitumoral action of bacterial lysates was characterized.

Further evidence for immunostimulatory effects of "foreign" DNA has been reported since the 1960's, describing the induction of interferon gamma production as well as activation of natural killer cells and induction of antitumoral activity by fractions of Bacillus Calmette-Guerin (BCG ) The immunostimulatory activity of this fraction could be destroyed by pre-incubation with DNAses, but not with RNAses, suggesting that the bacterial DNA constitutes the immunostimulatory portion of the BCG fraction, and detailed examination of the immunologically active DNA sequences revealed that these are oligonucleotides consisting of a central palindrome with a CpG motif.

Further investigations led to the hypothesis that the motive important for the immunostimulatory effect consists of a central CpG group (a dinucleotide of cytosine and guanine), which at the 5'-end of two purines and at the 3'-end of two pyrimidines flanked .DNA- sequences with the consensus sequence δ ^'-A / GA / GCGC / TC / ^TS' are referred to as CpG. CpG dinucleotides are suppressed in eukaryotic DNA.

These motifs occur in eukaryotic DNA only at a quarter of the expected frequency and are also mostly methylated on cytosine. In contrast, the CpG motif is unmethylated in bacterial DNA and at the expected frequency (1:16). It has been shown that methylation destroys the stimulatory potential of the CpG motif. These differences between bacterial and eukaryotic DNA make it possible to meaningfully interpret the biological observations regarding the immunostimulatory effect of bacterial DNA and synthetic oligonucleotides (ODN) with CpG motif (CpG-ODN). Obviously, recognition of CpG motifs is part of a conserved defense mechanism of the vertebrate immune system, to protect against the penetration of microbial pathogens. CpG-containing DNA is recognized by cells of the innate immune system as a molecular pattern for the presence of a pathogen and triggers an immune reaction as a danger signal, which is suitable to combat a microbial infection. Synthetic oligonucleotides containing CpG motifs (CpG-ODN) mimic bacterial DNA and can potentiate an immune response in vitro and in vivo.

The detection of "foreign" DNA and the subsequent immunological reaction is a way for the innate immune system to differentiate between "self" and "foreign", without relying on mediation or intervention of the adaptive immune system CpG motifs are therefore included the so-called PAMPs (Pathogen Associated Molecular Patterns).

CpG motifs are recognized by TLR-9 (Toll-like Receptor-9). TLR-9 is a member of the family of Toll-like receptors that serve pattern recognition to detect microbial infections. These receptors recognize conserved molecular structures of various microorganisms, such as bacteria, fungi, protozoa or viruses. So far, eleven members of this receptor family have been identified, with corresponding ligands are now known in most cases. Thus, e.g. TLR4 bacterial lipopolysaccharides, TLR3 double-stranded RNA, TLR7 / 8 single-stranded RNA motifs and TLR9 CpG motifs as previously described.

B cells and plasmacytoid dendritic cells (pDCs) in humans are the cell types that are directly stimulated by CpG motifs. The activation of these cells then leads to an immunostimulatory cascade, resulting in the maturation, differentiation and proliferation of natural killer cells (NK cells), T cells and monocytes / macrophages. Therefore, oligonucleotides with CpG motif are currently being tested as adjuvants for boosting vaccinations. Due to their immunostimulatory effect, they are also being discussed as potential therapeutics in the fight against infections and in cancer therapy. Besides, they are used in the treatment of allergies and asthma tested because they cause a TH 1 -mediated immune environment. The efficacy of some CpG ODN is currently being tested in clinical trials.

Applicant's work has shown that CpG ODNs have an immunosuppressive effect on the skin. From this, a patent application emerged (WO 2004/012688).

Over the last few years, it has been found that CpG motifs vary significantly in sequence and backbone (phosphorothioate, phosphodiester, or mixer) in terms of profile and kinetics of their immunostimulating action. Thus, three major classes of CpG ODN are currently distinguished: CpG A (also CpG D), CpG B (also CpG K) and CpG C ODN.

The structure of CpG-A is characterized by a chimeric backbone: the 5 ^' and 3 ^' ends are phosphorothioate-modified for increased stability against nucleases, while the middle region consists of unmodified phosphodiesters. Unmodified phosphodiester oligonucleotides are rapidly degraded in vivo by endogenous nucleases. By chemical modification of the phosphodiester backbone, the so-called phosphorothioate modification, one achieves an increased stability of the ODN (oligo-deoxynucleotide) towards nucleases. In the phosphorothioate modification, an oxygen atom of the phosphate group not involved in the bond is replaced by a sulfur atom.

CpG A ODNs usually have only one CpG motif embedded in a palindromic sequence. In addition, at the 5 'and 3' ends, they have sequences of guanines, which are probably important for the uptake of the oligonucleotides and the intracellular localization. Characteristic of the action of CpG-A ODN is the induction of IFN-α secretion by pDCs (plasmacytoid dendritic cells), which indirectly promotes maturation of antigen-presenting cells, and poor B cell activation.

CpG-B ODNs have a phosphorothioate backbone and often have multiple CpG motifs. At the δ 'end there is often a TCGTCG motif. in the Unlike CpG-A, CpG-B induces only very weak IFN-α production in pDC. Therefore, the IFN-dependent secondary effects of CpG-B on T cells, NK cells, γ / δ T cells and monocytes are significantly less pronounced than those of CpG-A. However, CpG-B ODN cause strong B cell activation (proliferation, IgM and cytokine production).

CpG-C-ODNs are a mixture of CpG-A and CpG-B-ODNs. Like the CpG-B ODNs, they have a phosphorothioate backbone, often possessing several CpG motifs and frequently at the 5'-end a TCGTCG motif. Like the CpG A ODN, they contain a central CpG motif embedded in a palindromic sequence. However, they lack the guanine episodes. Characteristic of the effect of CpG-C-ODN is that they combine some stimulatory properties of the A and B types. Thus, they lead both to the induction of IFN-α secretion by pDCs and to the activation of B cells.

However, the use of CpG ODN as an anti-inflammatory agent on the skin is not completely free of risks. In a murine model for the contact hypersensitivity reaction of type IV (triggered by 2,4-dinitrofluorobenzene), it could be shown that after subcutaneous administration of a CpG ODN, the reaction was significantly enhanced. A control ODN without CpG motif showed no effect. The authors conclude that CpG ODNs may worsen T cell-mediated skin diseases (Akiba H, Satoh M, Iwatsuki K, Kaiserlian D, Nicolas JF, Kaneko F: CpG immunostimulatory sequences enhance contact hypersensitivity responses in mice.) J Invest Dermatol; 123: 488-493, 2004). The topical use of CpG ODN could therefore in fact entail the risk that they stimulate immune cells in the event of a deep penetration into the skin and thus even lead to a worsening of inflammatory skin diseases.

Although these findings are only of limited significance, since murine and human systems have crucial differences in the recognition of CpG ODN, as described in the dissertation by Anja Marschner, p. 29, 30; Chapter 1.8.5, Available online on 26.01.2006 at http://edoc.ub.uni-muenchen.de/archive/00002874/01/Marschner Anja K.pdf.

It has been found that ODN, which are composed only of guanidine nucleotides (poly-G homopolymers), have a strong immunosuppressive action on skin cells (DE 10361502).

However, these ODNs are difficult to synthesize due to the properties of the nucleotide (low coupling efficiency in the synthesis) and, moreover, tend to form gel-like secondary and tertiary structures, which makes drug-like synthesis of such ODN very difficult. The ability to formulate ODN into effective drug formulations is also strongly negatively affected.

Nevertheless, there is a great need for new, topically applicable immunosuppressive agents that avoid the disadvantages and risks of the prior art as much as possible.

Surprisingly, it has been found that nucleic acids without a CpG motif which comprise sequences suitable for the formation of stem-loop secondary structures exert an immunosuppressive effect on topical application to the skin. Due to the lower guanidine content, they are also easier to produce than the poly-G homopolymers.

The present invention therefore relates to a cosmetic or pharmaceutical preparation for the prophylaxis and / or treatment of epithelial covering tissue, in particular for the prophylaxis and / or treatment of inflammatory epithelial covering tissue, which comprises nucleic acids without CpG motif, which are used to form stem-loop secondary structures comprise suitable sequences.

The preparation according to the invention may contain the nucleic acids without CpG motif, the sequences which are suitable for the formation of stem-loop secondary structures also in combination with other suitable, in particular anti-inflammatory agents (eg corticosteroids).

Nucleic acids without a CpG motif which comprise sequences suitable for the formation of stem-loop secondary structures are to be understood as meaning nucleic acids which a) do not contain a CpG motif and b) contain at least one sequence which can fold back on itself; wherein two essentially mirror-symmetric subsequences form the stem and an area lying between the subsequences forms the loop. The stem essentially has Watson-Crick base pairs.

The sequence of a DNA is a string describing it. Specifically, it defines the linear sequence of their bases and thus essentially determines the physical and chemical properties of the DNA. The chain is also called the primary structure of DNA.

In nature, DNA rarely occurs as a single chain. Rather, pairings can form between individual bases that are located on the same DNA strand. It is said that a strand of DNA folds back on itself. Mainly pairings occur between complementary bases (e.g., A and T, C and G), but also (much less frequently) between other bases.

The term mirror-symmetric subsequences in this context means that the ODN according to the invention contains at least two subsequences which are suitable for generating a double-stranded region by base pairing of subsequences or regions of these subsequences, the so-called stem, the bases of these preferably being Partial sequences are largely or substantially complementary to each other. The stem in particular has Watson-Crick base pairs. The secondary structure of a DNA now describes which bases are paired with it. It contains more information than the sequence. A distinction is made between so-called stars (these are connected structures that consist only of base pairings) and all other arrangements that are called loops.

Preferably, the two essentially mirror-symmetric partial sequences which form the stem essentially by Watson-Crick base pairing of complementary bases, in each case at least 2, preferably 3 or more, more preferably 3 to 10 nucleotides. Irrespective of this, it is preferred for the loop to have at least a length of 2, preferably 3 or more bases, so that at least 2, preferably 3 or more, bases which do not undergo base pairing lie between the two partial sequences which form the stem.

Whether a sequence can form a stem-loop structure can be predicted by means of suitable computer programs, for example with the URL http://www.bioinfo.rpi.edu/applications/mfold/old/dna/form1.cgionline (version 3.1 on January 30, 2006) available from Michael Zuker (Mfold web server for nucleic acid folding and hybridization prediction, Nucleic Acids Res. 31 (13), 3406-15, (2003)).

Preferably, nucleic acids without CpG motif which comprise sequences suitable for the formation of stem-loop secondary structures according to the invention preferably contain C-, G- or L-rich sequences with a content of .sym. At the 5 'and / or 3' end of the star of C, G or I in the range of 25% to 100%, preferably 50% to 100%, more preferably 75% to 100% and most preferably 100% (ie homopolymers).

The length of the C-, G- or L-rich, particularly preferably G-rich sequences is preferably in the range from 2 to 12 nucleotides, in particular in the range from 2 to 10 nucleotides, preferably in the range from 2 to 8 nucleotides, more preferably in Range of 2 to 6 nucleotides, and most preferably in the range of 4 to 6 nucleotides. The C, G or L rich, more preferably G-rich sequences can either be located only on one side of the star (in which case the 3'-end is preferred) or, more preferably, be located on either side of the star.

When the C, G or I rich, more preferably G-rich sequences are located on either side of the star, there may be a symmetric arrangement (the C, G or I rich sequences are exactly opposite each other), or an asymmetric arrangement (the C, G or I rich sequences are not exactly opposite each other). The asymmetric arrangement is preferred.

Preference is given to poly-1-homopolymers, poly-C-homopolymers or poly-G-homopolymers; particularly preferably poly-1-homopolymers or poly-G-homopolymers. Very particular preference is given to poly-G homopolymers. C is cytosine, G is guanine and I is inosine.

Most preferred is an array of 4 guanines at the 5 'end of the star and 6 guanines at the 3' end of the star.

Nucleic acids without CpG motif which can be used according to the invention and contain sequences suitable for the formation of stem-loop secondary structures have a length of 10 to 100, in particular 10 to 40, preferably 10 to 30, preferably 13 to 27 and very particularly preferably 16 to 24 nucleotides.

The nucleic acids without CpG motif which can be used according to the invention and comprise sequences suitable for the formation of stem-loop secondary structures can be of eukaryotic or prokaryotic origin (also hydrolyzed or partially hydrolyzed). Synthetic DNA is preferred according to the invention, however.

The nucleic acids without CpG motif which can be used according to the invention and which comprise sequences suitable for the formation of stem-loop secondary structures can be completely (all nucleotides) or partially (only a few nucleotides) chemically modified. Preferred modifications are, for example:

a) Alteration of the internucleoside bridges: Exchange of phosphodiesters for methylphosphonates, phosphoramidates, phosphorothioates (PTO) or hydroxylamines;

b) Modification of the sugar components: Exchange of the ribose for various hexo- or pentopyranoses or 3'-5'-carbocyclic bridged derivatives of 2'-deoxy ribose.

c) replacement of the strand backbone: replacement of the polyester chains based on sugar-phosphate units by carboxamide chains based on amino acid derivatives such as N- (2-aminoethyl) -glycine units;

Particularly preferred according to the invention are phosphorothioate-phosphodiester mixmers.

In the context of the present invention, epithelial covering tissue is understood as meaning, on the one hand, the skin covering the outer body surface (consisting of subcutis, corium and epidermis), on the other hand the tissue lining the hollow organs and body cavities, including the epithelia of the uterus and the mouth. In particular, skin and mucous membrane (especially conjunctiva, oral, nasal, vaginal and intestinal mucosa) should be understood. Particularly preferred is the application to keratinizing epithelia.

"Inflammatory changes" in the context of the present invention means "affected by an acute or chronic inflammation". Inflammation may be due to biological (eg, pathogens, autoimmune reactions, TNFs), chemical (eg, poisons, irritants), or physical (eg, ultraviolet radiation, osmotic changes, mechanical stress, heat stress) noxious or stressors be. An acute inflammation is characterized by sudden onset with rapid, often violent course over hours or days.

Cardinal symptoms of acute inflammation are rubor (redness due to vasodilation), tumor (tissue swelling due to inflammatory exudate), calor (heating due to increased tissue perfusion), dolor (pain due to nerve irritation) and functio leasa (disturbed function).

The different phases of an acute inflammation are controlled by the following mediators:

a) Cellular mediators: biogenic vasoactive amines (histamine and serotonin), arachidonic acid derivatives (leukotrienes, prostaglandins, prostacyclin, thromboxane A2), platelet-activating factor (PAF), cytokines (interleukins, TNF-D, interferons), NO.

b) Plasma mediators: complement system, coagulation and fibrinolytic system, kallikrein-kinin system

The best known forms of acute inflammation are exudative inflammation, serous inflammation, fibrinous inflammation, purulent inflammation, haemorrhagic inflammation, necrotizing and ulcerating inflammation, gangrenous inflammation and acute lymphocytic inflammation.

On the other hand, chronic inflammation is characterized by a long course (weeks, months, or years) with often creeping onset and developing symptoms, in particular persistence of the injury.

The preparation according to the invention is particularly suitable for the prophylaxis and treatment of the following inflammatory changes, diseases or undesirable conditions: inflammatory aging processes, psoriasis, atopic eczema, seborrheic eczema, scleroderma, "dry skin", alopecia arreata, vitiligo, bullous disorders, lupus erythematodis, Repulsion reactions (graft-versus-host reactions), radiation-related, especially UV-related skin inflammations, toxic contact dermatitis, irritation and inflammation of the mucous membranes, in particular nasal irritation and vulvovaginitis, angular cornering and functional disorders of the epidermal barrier, listed on page 2 of WO 98/32444 which are hereby incorporated by reference.

As mentioned above, CpG ODNs can induce or enhance a Th1 immune response. Non-CpG ODNs (ODN without CpG motif) can be used to treat Th 1 -mediated reactions as they stimulate a Th2 immune response and thus inhibit Th 1 -mediated responses. It has now been found that Th2-mediated reactions can also be treated with the non-CpG ODN according to the invention.

The Th2-mediated diseases to be treated according to the invention include in particular diseases of the atopic type, in particular hay fever, atopic dermatitis (atopic dermatitis, atopic dermatitis), exogenous bronchial asthma, allergic enteritis, allergic conjunctivitis, hives and other allergic skin diseases.

A preferred inflammatory disease of the gums (the oral mucosa) to be treated with the aid of a preparation according to the invention is periodontosis. Periodontal disease is an infectious disease caused in most cases by the bacteria Porphyramonas gingivalis, Bacteroides forsythus and Actinobacillus actinomycetemcomitans. The presence of bacteria is a necessary but not sufficient precondition for the onset of the disease. The continuous release of harmful substances, especially lipopolysaccharides, by the bacteria activates the immune system of the host and triggers the release of inflammatory mediators and MMPs (matrix metallo-proteases) by the monocytes. Proinflammatory cytokines, such as IL-1β and TNF-α, in turn, activate the fibroblasts of the surrounding tissue, which in turn enhance the secretion of MMPs. Activated macrophages and fibroblasts also reduce the Expression of TIMPs (tissue inhibitor of metallogroteinase). The result is an increase in the net activity of MMPs and the destruction of surrounding tissue.

In the early stages of periodontal disease, the MMP-mediated dissolution of small amounts of connective epithelial tissue between the gum and the root surface of the tooth creates a pocket that provides the bacteria access to the deeper layers, thus allowing the disease to progress. The reduction of extracellular matrix destruction is therefore a promising approach for the treatment and prevention of periodontal disease.

The nucleic acids supplied to the epithelial covering tissue with the aid of the preparation according to the invention ensure suppression of the excess immune response in the epithelial covering tissue and thus a controlled balance between the formation and breakdown of collagen.

In contrast to steroid therapy, unwanted effects can not be expected when using the preparation according to the invention, since stem-loop structures represent naturally occurring DNA secondary structures.

According to a preferred embodiment, the preparations according to the invention are applied topically to the epithelial cover tissue.

The nucleic acids without CpG motif which can be used according to the invention and which comprise sequences suitable for the formation of stem-loop secondary structures can be chemically synthesized in a manner known to the person skilled in the art or can be obtained from biological sources, in particular from bacteria.

The efficacy of nucleic acids in formulations for use particularly on the skin depends on the availability of the nucleic acids in the living cells of the skin. The penetration of a macromolecule through the stratum corneum (natural barrier of the skin) into the skin is not always guaranteed. However, nucleic acids packaged in liposomes may be stratum Penetrate corneum of skin models. Preparations preferred according to the invention are therefore those which comprise the nucleic acids which can be used according to the invention and which have no CpG motif and which comprise sequences suitable for the formation of stem-loop secondary structures, packed in liposomes. Equally preferred are preparations containing other suitable carrier systems, for. As nanotechnology-based systems or penetration enhancers (for example, urea, Azone or DMSO) included.

Particular preference is given to the preparation of suitable liposomes as described in DE-A-197 40 092, to which reference is hereby fully made.

Another object of the present invention is the use of nucleic acids without CpG motif, which comprise sequences suitable for the formation of stem-loop secondary structures, for the prophylaxis and / or treatment of epithelial cover tissue, in particular for the prophylaxis and / or treatment of inflammatory epithelial cover tissue.

Another object of the present invention is a process for the preparation of a cosmetic or pharmaceutical preparation, in particular for the prophylaxis and / or treatment of inflamed epithelial cover tissue, characterized in that nucleic acids without CpG motif, which are suitable for the formation of stem-loop secondary structures Sequences include, as described for the preparations according to the invention, mixed with cosmetically and pharmacologically suitable and compatible carriers.

Further objects of the present invention are fabric softeners, hand washing agents, body and hair care products, hair dyes or hand dishwashing detergents which comprise nucleic acids without CpG motif which comprise sequences suitable for the formation of stem-loop secondary structures, as described for the preparations according to the invention. include. For the purposes of the present invention, the nucleic acids without CpG motif which comprise sequences suitable for the formation of stem-loop secondary structures are preferably incorporated or incorporated as a component in a cosmetic or pharmaceutical preparation or in fabric softeners, hand washing agents, hand dishwashing detergents or personal care products.

Depending on the nature of the formulation, the pharmaceutical compositions of the invention may contain at least one further auxiliary or additive, such as. As oils, protective colloids, plasticizers, antioxidants and / or emulsifiers. In the case of a dispersion, especially in the case of a suspension or emulsion, it is advantageous, in addition to a physiologically acceptable oil such as sesame oil, corn oil, cottonseed oil, soybean oil or peanut oil, esters of medium-chain fatty acids or fish oils such as mackerel, sprat or salmon oil use.

To increase the stability of the active ingredient against oxidative degradation, it is advantageous to add stabilizers such as a-tocopherol, t-butylhydroxytoluene, t-butylhydroxyanisole, ascorbic acid or ethoxyquine.

The dosage and duration of use of the inventively employable nucleic acids without CpG motif, which comprise sequences suitable for the formation of stem-loop secondary structures, can be suitably adapted and varied by the person skilled in the art.

The laundry softeners according to the invention, hand washing agents and hand dishwashing detergents and the cosmetic preparations, body and hair care products and hair colorants, such as hair shampoos, hair lotions, bubble baths, shower baths, creams, gels, lotions, alcoholic and aqueous / alcoholic solutions, emulsions, wax / fat masses, Stick preparations, powders or ointments may - depending on the nature of the formulation - as auxiliaries and mild surfactants, oils, emulsifiers, superfatting agents, pearlescing, consistency, thickeners, polymers, silicone compounds, fats, waxes, stabilizers, biogenic agents, deodorants, antiperspirants, Anti-dandruff agent, film former, swelling agent, UV Sunscreens, antioxidants, hydrotropes, preservatives, insect repellents, self-tanning agents, solubilizers, perfume oils, dyes and the like.

Typical examples of suitable mild, i. particularly skin-compatible surfactants are fatty alcohol polyglycol ether sulfates, monoglyceride sulfates, mono- and / or dialkyl sulfosuccinates, fatty acid isethionates, fatty acid sarcosinates,

Fatty acid taurides, fatty acid glutamates, α-olefinsulfonates, ether carboxylic acids, alkyl oligoglucosides, fatty acid glucamides, alkylamido betaines and / or protein fatty acid condensates, the latter preferably based on wheat proteins.

Guerbet alcohols based on fatty alcohols having 6 to 18, preferably 8 to 10, carbon atoms, esters of linear C ₆ -C ₂ -fatty acids with linear C ₆ -C ₂₂ -fatty alcohols, esters of branched C ₆ -C 13 -carboxylic acids are included as oil bodies linear C ₆ -C ₂₂ -fatty alcohols, such as myristyl myristate, myristyl palmitate, myristyl stearate, Myristylisostearat, myristyl, Myristylbehenat, Myristylerucat, cetyl myristate, cetyl palmitate, cetyl stearate, Cetylisostearat, cetyl oleate, cetyl behenate, Cetylerucat, Stearylmyristat, stearyl palmitate, stearyl stearate, Stearylisostearat, stearyl oleate, stearyl behenate , Stearylerucat, isostearyl, isostearyl palmitate, Isostearylstearat, isostearyl isostearate, Isostearyloleat, isostearyl behenate, Isostearyloleat, oleyl myristate, oleyl palmitate, oleyl stearate, oleyl isostearate, oleyl oleate, Oleylbehenat, oleyl erucate, behenyl myristate, behenyl palmitate, behenyl, Behenylisostearat, behenyl oleate, behenyl behenate, behenyl erucate, Erucylmyr isatate, erucyl palmitate, erucyl stearate, erucyl isostearate, erucyl oleate, erucyl behenate and erucyl erucate.

In addition, esters of linear C ₆ -C ₂₂ fatty acids with branched alcohols, in particular 2-ethylhexanol, esters of hydroxycarboxylic acids with linear or branched C ₆ -C ₂₂ fatty alcohols, in particular dioctyl malates, esters of linear and / or branched fatty acids with polyhydric alcohols (for example propylene glycol, dimer diol or trimer triol) and / or Guerbet alcohols, triglycerides based on C ₆ -C ₀ fatty, liquid mono- / di- / Triglyceride mixtures based on C ₆ -C ₈ fatty acids, esters of C ₆ -C ₂₂ - fatty alcohols and / or Guerbet alcohols with aromatic carboxylic acids, in particular benzoic acid, esters of C ₂ -C ₂ dicarboxylic acids with linear or branched alcohols having 1 to 22 carbon atoms or polyols having 2 to 10 carbon atoms and 2 to 6 hydroxyl groups, vegetable oils, branched primary alcohols, substituted cyclohexanes, linear and branched C ₆ -C ₂₂ fatty alcohol carbonates, Guerbet carbonates, esters of benzoic acid with linear and / or branched C ₆ -C ₂₂ -alcohols (eg Finsolv ^® TN), linear or branched, symmetrical or asymmetrical dialkyl ethers having 6 to 22 carbon atoms per alkyl group, ring-opening products of epoxidized fatty acid esters with polyols, silicone oils and / or aliphatic or naphthenic hydrocarbons, such as. As squalane, squalene or dialkylcyclohexanes.

Examples of suitable emulsifiers are nonionic surfactants from at least one of the following groups:

(1) addition products of 2 to 30 moles of ethylene oxide and / or 0 to 5 moles of propylene oxide to linear fatty alcohols having 8 to 22 carbon atoms, to fatty acids having 12 to 22 carbon atoms, to alkylphenols having 8 to 15 carbon atoms in the Alkyl group and alkylamines having 8 to 22 carbon atoms in the alkyl radical;

(2) Ci _{2 /} i ₈ fatty acid monoesters and diesters of addition products of 1 to 30 mol ethylene oxide onto glycerol;

(3) glycerol mono- and diesters and sorbitan mono- and diesters of saturated and unsaturated fatty acids having 6 to 22 carbon atoms and their ethylene oxide addition products;

(4) alkyl and / or alkenyl mono- and oligoglycosides having 8 to 22 carbon atoms in the alk (en) yl radical and their ethoxylated analogs;

(5) addition products of 15 to 60 moles of ethylene oxide with castor oil and / or hydrogenated castor oil;

(6) polyol and especially polyglycerol esters;

(7) addition products of 2 to 15 moles of ethylene oxide with castor oil and / or hydrogenated castor oil; (8) _{partial esters} based on linear, branched, unsaturated or saturated C _6/22 fatty acids, ricinoleic acid and 12-hydroxystearic acid and glycerol, polyglycerol, pentaerythritol, dipentaerythritol, sugar alcohols (eg sorbitol), alkyl glucosides (eg methyl glucoside, butyl glucoside, lauryl glucoside) as well as polyglucosides (eg cellulose);

(9) mono-, di- and trialkyl phosphates and mono-, di- and / or tri-PEG-alkyl phosphates and their salts;

(10) wool wax alcohols;

(11) polysiloxane-polyalkyl-polyether copolymers or corresponding derivatives;

(12) mixed esters of pentaerythritol, fatty acids, citric acid and fatty alcohol according to DE 1165574 PS and / or mixed esters of fatty acids having 6 to 22 carbon atoms, methyl glucose and polyols, preferably glycerol or polyglycerol,

(13) Polyalkylene glycols as well

(14) Glycerol carbonate.

The addition products of ethylene oxide and / or of propylene oxide to fatty alcohols, fatty acids, alkylphenols, glycerol mono- and diesters and sorbitan mono- and diesters of fatty acids or to castor oil are known, commercially available products.

These are homolog mixtures whose mean degree of alkoxylation corresponds to the ratio of the molar amounts of ethylene oxide and / or propylene oxide and substrate with which the addition reaction is carried out. C _12/1 8- fatty acid mono- and diesters of addition products of ethylene oxide onto glycerol are known from DE 2024051 as refatting agents for cosmetic preparations.

Alkyl and / or alkenyl mono- and oligoglycosides, their preparation and their use are known in the art. They are prepared in particular by reacting glucose or oligosaccharides with primary alcohols having 8 to 18 carbon atoms. With regard to the glycoside residue, it applies that both monoglycosides in which a cyclic sugar residue is glycosidically attached to the Fatty alcohol is bound, as well as oligomeric glycosides having a degree of oligomerization to preferably about 8 are suitable. The degree of oligomerization is a statistical mean, which is based on a homolog distribution typical for such technical products.

Typical examples of suitable polyglycerol esters are Polyglyceryl-2 Dipolyhydroxystearate (Dehymuls ^® PGPH), Polyglycerin-3-Diisostearate (Lameform ^® TGI), Polyglyceryl-4 Isostearate (Isolan ^® GI 34), Polyglyceryl-3 Oleate, Diisostearoyl Polyglyceryl-3 Diisostearate (Isolan ^® PDI), Polyglyceryl-3 methylglucose Distearate (Tego Gare ^® 450), Polyglyceryl-3 Beeswax (Gera Bellina ^®), Polyglyceryl-4 Caprate (polyglycerol Caprate T2010 / 90), Polyglyceryl-3 Cetyl ether (Chimexane ^® NL), Polyglyceryl -3 Distearate (Cremophor ^® GS 32) and Polyglyceryl polyricinoleates (Admul ^® WOL 1403), polyglyceryl dimerates Isostearate and mixtures thereof.

Furthermore, zwitterionic surfactants can be used as emulsifiers. Zwitterionic surfactants are those surface-active compounds which carry at least one quaternary ammonium group and at least one carboxylate and one sulfonate group in the molecule. Particularly suitable zwitterionic surfactants are the so-called betaines such as the N-alkyl-N, N-dimethylammoniumglycinate, for example the

Kokosalkyldimethylammoniumglycinat, N-acylaminopropyl-N, N-dimethylammoniumglycinate, for example Kokosacyl- aminopropyldimethylammoniumglycinat, and 2-alkyl-3-carboxylmethyl-3-hydroxyethylimidazoline having in each case 8 to 18 carbon atoms in the alkyl or acyl group and Kokosacylaminoethylhydroxyethylcarboxymethylglycinat. Particularly preferred is the fatty acid amide derivative known under the CTFA name Cocamidopropyl Betaine. Also suitable emulsifiers are ampholytic surfactants. Ampholytic surfactants are surface-active compounds which, apart from a _{C8 /} i ₈ alkyl or - acyl group in the molecule and at least one at least one free amino group - COOH or -SO ₃ H group and are capable of forming inner salts , Examples of suitable ampholytic surfactants are N-alkylglycines, N-alkyl alkylpropionic acids, N-alkylaminobutyric acids, N-alkyliminodipropionic acids, N-hydroxyethyl-N-alkylamidopropylglycines, N-alkyltaurines, N-alkylsarcosines, 2-alkylaminopropionic acids and alkylaminoacetic acids each having about 8 to 18 C atoms in the alkyl group. Particularly preferred ampholytic surfactants are N-cocoalkylaminopropionate, cocoacylaminoethylaminopropionate and _C 12/18 acylsarcosine. In addition to the ampholytic, quaternary emulsifiers are also suitable, with those of the esterquat type, preferably methyl-quaternized difatty acid triethanolamine ester salts, being particularly preferred.

Superfatting agents may be substances such as lanolin and lecithin, as well as polyethoxylated or acylated lanolin and lecithin derivatives, polyol fatty acid esters, monoglycerides and fatty acid alkanolamides, the latter also serving as foam stabilizers.

Suitable pearlescing waxes are, for example: alkylene glycol esters, especially ethylene glycol distearate; Fatty acid alkanolamides, especially

coconut fatty acid diethanolamide; Partial glycerides, especially stearic acid monoglyceride; Esters of polybasic, optionally hydroxy-substituted carboxylic acids with fatty alcohols having 6 to 22 carbon atoms, especially long-chain esters of tartaric acid; Fatty substances, such as fatty alcohols, fatty ketones, fatty aldehydes, fatty ethers and fatty carbonates, which in total have at least 24 carbon atoms, especially lauron and distearyl ether; Fatty acids such as stearic acid, hydroxystearic acid or behenic acid, ring-opening products of olefin epoxides having 12 to 22 carbon atoms with fatty alcohols having 12 to 22 carbon atoms and / or polyols having 2 to 15 carbon atoms and 2 to 10 hydroxyl groups and mixtures thereof.

As consistency factors are primarily fatty alcohols or hydroxy fatty alcohols having 12 to 22 and preferably 16 to 18 carbon atoms and in addition partial glycerides, fatty acids or hydroxy fatty acids into consideration. A combination of these substances with alkyl oligoglucosides and / or fatty acid N is preferred. methylglucamides of the same chain length and / or polyglycerol poly-12-hydroxystearaten.

Suitable thickening agents are, for example, Aerosil types (hydrophilic silicas), polysaccharides, in particular xanthan gum, guar guar, agar agar, alginates and tyloses, carboxymethyl cellulose and hydroxyethyl cellulose, furthermore higher molecular weight polyethylene glycol mono- and diesters of fatty acids, polyacrylates, (eg Carbopols ^® from Goodrich or Synthalene ^® from Sigma), polyacrylamides, polyvinyl alcohol and polyvinylpyrrolidone, surfactants such as ethoxylated fatty acid glycerides, esters of fatty acids with polyols such as pentaerythritol or trimethylolpropane, fatty alcohol ethoxylates with narrow homolog distribution or alkyl oligoglucosides and electrolytes such as saline and ammonium chloride.

Suitable cationic polymers are, for example, cationic cellulose derivatives, such as, for example, a quaternized hydroxyethylcellulose which is obtainable under the name Polymer JR 400® from Amerchol, cationic starch, copolymers of diallylammonium salts and acrylamides, quaternized vinylpyrrolidone / inylimidazole polymers, such as, for example, Luviquat® (BASF) , Condensation products of polyglycols and amines, quaternized collagen polypeptides such as lauryldimonium hydroxypropyl hydrolyzed collagen (Lamequat®L / Grünau), quaternized wheat polypeptides, polyethylenimine, cationic silicone polymers such as amidomethicones, copolymers of adipic acid and dimethylaminohydroxypropyldiethylenetriamine (Cartaretine® / Sandoz), copolymers of Acrylic acid with dimethyldiallylammonium chloride (Merquat® 550 / Chemviron), polyaminopolyamides, as described, for example, in FR 2252840 A and their crosslinked water-soluble polymers, cationic chitin derivatives such as, for example, quaternized chitosa n, optionally microcrystalline distributed, condensation products of dihaloalkylene, such as dibromobutane with bis-dialkylamines, such as bis-dimethylamino-1, 3-propane, cationic guar gum, such as Jaguar® CBS, Jaguar® C-17, Jaguar® C-16 of the Celanese, quaternized ammonium salt polymers such as Mirapol® A-15, Mirapol® AD-1, Mirapol® AZ-1 from Miranol.

Examples of anionic, zwitterionic, amphoteric and nonionic polymers are vinyl acetate / crotonic acid copolymers, vinylpyrrolidone / vinyl acrylate copolymers, vinyl acetate / butyl maleate / isobornyl acrylate copolymers,

Methyl vinyl ether / maleic anhydride copolymers and their esters, uncrosslinked and polyols crosslinked polyacrylic acids, acrylamidopropyltrimethylammonium chloride / acrylate copolymers, octylacrylamide / methyl methacrylate / tert.butylaminoethyl methacrylate / 2-hydroxypropyl methacrylate copolymers, polyvinylpyrrolidone, vinylpyrrolidone / inylacetate copolymers, Vinylpyrrolidone / DimethylaminoethylmethacrylatA / inylcaprolactam terpolymers and optionally derivatized cellulose ethers and silicones in question.

Suitable silicone compounds are, for example, dimethylpolysiloxanes, methylphenylpolysiloxanes, cyclic silicones and amino, fatty acid, alcohol, polyether, epoxy, fluorine, glycoside and / or alkyl-modified silicone compounds which may be both liquid and resin-form at room temperature. Also suitable are simethicones, which are mixtures of dimethicones having an average chain length of from 200 to 300 dimethylsiloxane units and hydrogenated silicates. A detailed overview of suitable volatile silicones can also be found in Todd et al. in Cosm.Toil. 91, 27 (1976).

Typical examples of fats are glycerides, as waxes include natural waxes, such as candelilla wax, carnauba wax, Japan wax, Espartograswachs, cork wax, guaruma wax, rice germ oil, sugar cane wax, ouricury wax, montan wax, beeswax, shellac wax, spermaceti, lanolin (wool wax), cushioned fat , Ceresin, ozokerite (groundwax), petrolatum, paraffin waxes, microwaxes; chemically modified waxes (hard waxes), such as montan ester waxes, Sasol waxes, hydrogenated jojoba waxes and synthetic waxes, such as polyalkylene waxes and polyethylene glycol waxes in question. As stabilizers metal salts of fatty acids, such as magnesium, aluminum and / or zinc stearate or ricinoleate can be used.

Biogenic active ingredients are, for example, tocopherol, tocopherol acetate, tocopherol palmitate, ascorbic acid, deoxyribonucleic acid, retinol, bisabolol, allantoin, phytantriol, panthenol, AHA acids, amino acids, ceramides, pseudoceramides, essential oils, plant extracts and vitamin complexes.

Cosmetic deodorants (deodorants) counteract, cover or eliminate body odors. Body odors are caused by the action of skin bacteria on apocrine sweat, forming unpleasant-smelling degradation products. Accordingly, deodorants contain active ingredients which act as anti-sprouting agents, enzyme inhibitors, odor absorbers or odor maskers.

As germ-inhibiting agents, which are optionally added to the cosmetics of the invention, in principle all substances effective against gram-positive bacteria are suitable, such as. For example, 4-hydroxybenzoic acid and its salts and esters, N- (4-chlorophenyl) -N ^' - (3,4-dichlorophenyl) urea, 2,4,4'-trichloro-2 ^' - hydroxydiphenyl ether (triclosan), 4-chloro -3,5-dimethylphenol, 2,2 ^{'methylene-bis} (6-bromo-4-chlorophenol), 3-methyl-4- (1-methylethyl) phenol, 2-benzyl-4-chlorophenol, 3- (4 -Chlorophenoxy) -1,2-propanediol, 3-iodo-2-propynyl butylcarbamate, chlorhexidine, 3,4,4'-trichlorocarbanilide (TTC), antibacterial fragrances, thymol, thyme oil, eugenol, clove oil, menthol, mint oil, farnesol, phenoxyethanol , Glycerol monolaurate (GML), diglycerol monocaprinate (DMC), salicylic acid N-alkylamides such. Salicylic acid n-octylamide or salicylic acid n-decylamide.

Enzyme inhibitors can also be added to the cosmetics according to the invention. Suitable enzyme inhibitors are, for example, esterase inhibitors. These are preferably trialkyl citrates such as trimethyl citrate, tripropyl citrate, triisopropyl citrate, tributyl citrate and in particular triethyl citrate (Hydagen® ^® CAT, Henkel KGaA, Dusseldorf / FRG). The substances inhibit the enzyme activity and thereby reduce odors. Further substances which are suitable as esterase inhibitors are sterol sulfates or phosphates, such as, for example, lanosterol, cholesterol, campesterol, stigmasterol and sitosterol sulfate or phosphate, dicarboxylic acids and their esters, for example glutaric acid, glutaric acid monoethyl ester, glutaric acid diethyl ester, adipic acid, Adipic acid monoethyl ester, diethyl adipate, malonic acid and diethyl malonate, hydroxycarboxylic acids and their esters such as citric acid, malic acid, tartaric acid or diethyl tartrate, and zinc glycinate.

Suitable odor absorbers are substances that absorb and largely retain odor-forming compounds. They reduce the partial pressure of the individual components and thus also reduce their propagation speed. It is important that perfume must remain unimpaired. Odor absorbers have no activity against bacteria. They contain, for example, as a main component of a complex zinc salt of ricinoleic acid or special, largely odorless fragrances, which are known in the art as "fixatives", such. B. Extracts of Labdanum or Styrax or certain Abietinsäurederivate. Odor maskers are fragrances or perfume oils which, in addition to their function as odor maskers, give the deodorants their respective scent. Examples of perfume oils are mixtures of natural and synthetic fragrances. Natural fragrances are extracts of flowers, stems and leaves, fruits, fruit peel, roots, woods, herbs and grasses, needles and twigs, as well as resins and balsams. Furthermore, animal raw materials come into question, such as civet and Castoreum. Typical synthetic fragrance compounds are ester type products, ethers, aldehydes, ketones, alcohols and hydrocarbons. Fragrance compounds of the ester type are, for example, benzyl acetate, p-tert-butylcyclohexyl acetate, linalyl acetate, phenylethyl acetate, linalyl benzoate, benzyl formate, allylcyclohexyl propionate, styrallyl propionate and benzyl salicylate. The ethers include, for example, benzyl ethyl ether, to the aldehydes, for example, the linear alkanals with 8 to 18 Carbon atoms, citral, citronellal, citronellyloxyacetaldehyde,

Cyclamen aldehyde, hydroxycitronellal, lilial and bourgeonal, to the ketones e.g. the alcohols include anethole, citronellol, eugenol, isoeugenol, geraniol, linalool, phenylethyl alcohol and terpineol; the hydrocarbons mainly include the terpenes and balsams. Preferably, however, mixtures of different fragrances are used, which together produce an attractive fragrance. Also, lower volatility volatile oils, which are most commonly used as aroma components, are useful as perfume oils, e.g. Sage oil, chamomile oil, clove oil, lemon balm oil, mint oil, cinnamon leaf oil, lime blossom oil, juniper berry oil, vetiver oil, oliban oil, galbanum oil, labdanum oil and lavandin oil. Preferably, bergamot oil, dihydromyrcenol, lilial, lyral, citronellol, phenylethyl alcohol, α-hexylcinnamaldehyde, geraniol, benzylacetone, cyclamen aldehyde, linalool, Boisambrene Forte, Ambroxan, indole, hedione, Sandelice, citron oil, tangerine oil, orange oil, Allylamylglycolat, Cyclovertal, Lavandinöl, Muskateller Sage oil, β-damascone, geranium oil Bourbon, cyclohexyl salicylate, Vertofix Coeur, Iso-E-Super, fixolide NP, evernyl, iraldeine gamma, phenylacetic acid, geranyl acetate, benzyl acetate, rose oxide, romilate, irotyl and floramate alone or in mixtures.

Antiperspirants (antiperspirants) reduce the formation of sweat by influencing the activity of eccrine sweat glands and thus counteract underarm wetness and body odor. Aqueous or anhydrous formulations of antiperspirants typically contain the following ingredients:

(a) astringent agents,

(b) oil components,

(c) nonionic emulsifiers,

(d) coemulsifiers,

(e) bodybuilder,

(f) adjuvants such as. B. thickener or complexing agent and / or

(g) non-aqueous solvents such as. As ethanol, propylene glycol and / or glycerol. Salts of aluminum, zirconium or zinc are especially suitable as astringent antiperspirant active ingredients. Such suitable antiperspirant active ingredients are, for example, aluminum chloride, aluminum chlorohydrate, aluminum dichlorohydrate, aluminum sesquichlorohydrate and their complex compounds z. With propylene glycol-1, 2. Aluminum hydroxyalloinate, aluminum chloride tartrate, aluminum zirconium trichlorohydrate, aluminum zirconium tetrachlorohydrate, aluminum zirconium pentachlorohydrate and their complex compounds e.g. With amino acids such as glycine.

In addition, antiperspirants may contain customary oil-soluble and water-soluble adjuvants in smaller amounts. Such oil-soluble adjuvants may be e.g. be:

• anti-inflammatory, skin-protecting or fragrant essential oils,

• synthetic skin-protecting agents and / or

• oil-soluble perfume oils.

Usual water-soluble additives are e.g. Preservatives, water-soluble fragrances, pH adjusters, e.g. Buffer mixtures, water-soluble thickeners, e.g. water-soluble natural or synthetic polymers such as e.g. Xanthan gum, hydroxyethyl cellulose, polyvinyl pyrrolidone or high molecular weight polyethylene oxides.

Climbazole, octopirox and zinc pyrithione can be used as anti-dandruff agents.

Typical film formers are, for example, chitosan, microcrystalline chitosan, quaternized chitosan, polyvinylpyrrolidone, vinylpyrrolidone-vinyl acetate copolymers, polymers of the acrylic acid series, quaternary cellulose derivatives, collagen, hyaluronic acid or salts thereof and similar compounds.

Suitable swelling agents for aqueous phases are montmorillonites, clay minerals, pemulen and alkyl-modified carbopol types (Goodrich). Further Suitable polymers or swelling agents can be reviewed by R. Lochhead in Cosm.Toil. 108, 95 (1993).

Under UV sun protection factors, for example, at room temperature, liquid or crystalline organic substances (sunscreen) to understand that are able to absorb ultraviolet rays and the absorbed energy in the form of longer-wave radiation, e.g. Heat again. UVB filters can be oil-soluble or water-soluble. As oil-soluble substances are e.g. to call:

3-benzylidene camphor or 3-benzylidene norcamphor and its derivatives, e.g. 3- (4-methylbenzylidene) camphor as described in EP 0693471 B1;

4-aminobenzoic acid derivatives, preferably 4-dimethylamino) benzoic acid 2-ethylhexyl ester, 4- (dimethylamino) benzoic acid 2-octyl ester and 4- (dimethylamino) benzoic acid amyl ester;

Esters of cinnamic acid, preferably 4-methoxycinnamic acid 2-ethylhexyl ester, 4-methoxycinnamic acid propyl ester, 4-methoxycinnamic acid isoamyl ester 2-cyano-3,3-phenylcinnamic acid 2-ethylhexyl ester (octocrylene);

Esters of salicylic acid, preferably 2-ethylhexyl salicylate, 4-isopropylbenzyl salicylate, homomenthyl salicylate;

Derivatives of benzophenone, preferably 2-hydroxy-4-methoxybenzophenone, 2-hydroxy-4-methoxy-4'-methylbenzophenone, 2,2'-dihydroxy-4-methoxybenzophenone;

Esters of benzalmalonic acid, preferably di-2-ethylhexyl 4-methoxybenzmalonate;

Triazine derivatives, e.g. 2,4,6-Trianilino- (p-carbo-2'-ethyl-1'-hexyloxy) -1, 3,5-triazine and octyl triazone, as described in EP 0818450 A1 or dioctyl butamido triazone (Uvasorb® HEB );

Propane-1,3-diones, e.g. 1- (4-tert-butylphenyl) -3- (4'-methoxyphenyl) propane-1,3-dione;

Ketotricyclo (5.2.1.0) decane derivatives as described in EP 0694521 B1.

Suitable water-soluble substances are: 2-phenylbenzimidazole-5-sulfonic acid and its alkali, alkaline earth, ammonium, alkylammonium, alkanolammonium and glucammonium salts;

Sulfonic acid derivatives of benzophenones, preferably 2-hydroxy-4-methoxybenzophenone-5-sulfonic acid and its salts;

Sulfonic acid derivatives of the 3-benzylidene camphor, e.g. 4- (2-Oxo-3-bornylidenemethyl) benzenesulfonic acid and 2-methyl-5- (2-oxo-3-bomylidene) -sulfonic acid and its salts.

As a typical UV-A filter in particular derivatives of benzoylmethane come into question, such as 1- (4'-tert-butylphenyl) -3- (4'-methoxyphenyl) propane-1, 3-dione, 4-tert-butyl 4'-methoxydibenzoylmethane (Parsol 1789), 1-phenyl-3- (4'-isopropylphenyl) -propane-1, 3-dione and also enamine compounds as described in DE 19712033 A1 (BASF). Of course, the UV-A and UV-B filters can also be used in mixtures. In addition to the soluble substances mentioned, insoluble photoprotective pigments, namely finely dispersed metal oxides or salts, are also suitable for this purpose. Examples of suitable metal oxides are in particular zinc oxide and titanium dioxide and, in addition, oxides of iron, zirconium, silicon, manganese, aluminum and cerium and mixtures thereof. As salts silicates (talc), barium sulfate or zinc stearate can be used. The oxides and salts are used in the form of the pigments for skin-care and skin-protecting emulsions and decorative cosmetics. The particles should have an average diameter of less than 100 nm, preferably between 5 and 50 nm and in particular between 15 and 30 nm. They may have a spherical shape, but it is also possible to use those particles which have an ellipsoidal or otherwise deviating shape from the spherical shape. The pigments can also be surface-treated, ie hydrophilized or hydrophobized. Typical examples are coated titanium dioxides, such as titanium dioxide T 805 (Degussa) or Eusolex® T2000 (Merck). Suitable hydrophobic coating agents are in particular silicones and in particular trialkoxyoctylsilanes or simethicones. In sunscreens, so-called micro- or nanopigments are preferably used. Preferably, micronized zinc oxide is used. Further suitable UV photoprotective filters can be found in the review by P.Finkel in SÖFW-Journal 122, 543 (1996).

In addition to the two aforementioned groups of primary light stabilizers, it is also possible to use secondary light stabilizers of the antioxidant type which interrupt the photochemical reaction chain which is triggered when UV radiation penetrates into the skin. Typical examples are amino acids (eg glycine, histidine, tyrosine, tryptophan) and their derivatives, imidazoles (eg urocaninic acid) and their derivatives, peptides such as D, L-camosine, D-camosine, L-carnosine and their derivatives (eg anserine) , Chlorogenic acid and its derivatives, lipoic acid and its derivatives (eg dihydrolipoic acid), aurothioglucose, propylthiouracil and other thiols (eg thioredoxin, glutathione, cysteine, cystine, cystamine and their glycosyl, N-acetyl, methyl, ethyl, propyl) , Amyl, butyl and lauryl, palmitoyl, oleyl, γ-linoleyl, cholesteryl and glyceryl esters) and their salts, dilauryl thiodipropionate, distearyl thiodipropionate, thiodipropionic acid and derivatives thereof (esters, ethers, peptides, lipids, nucleotides, nucleosides and salts) as well as sulfoximine compounds (eg buthionine sulfoximines, homocysteine sulfoximine, bithine sulfones, penta, hexa, heptathionine sulfoximine) in very low compatible dosages (eg pmol to μmol / kg), furthermore (metal) - chelators (eg Hydroxy fatty acids, palmitic acid, phytic acid, lactoferrin), α-hydroxy acids (eg citric acid, lactic acid, malic acid), humic acid, bile acid, bile extracts, bilirubin, biliverdin, EDTA, EGTA and their derivatives, unsaturated fatty acids and their derivatives (eg γ-linolenic acid, Linoleic acid, oleic acid), folic acid and its derivatives, ubiquinone and ubiquinol and derivatives thereof, vitamin C and derivatives (eg ascorbyl palmitate, Mg ascorbyl phosphate, ascorbyl acetate), tocopherols and derivatives (eg vitamin E acetate), vitamin A and derivatives (vitamin A-palmitate) and coniferyl benzoate of benzoin, rutinic acid and derivatives thereof, α-glycosylrutin, ferulic acid, furfurylidene glucitol, carnosine, butylhydroxytoluene, butylhydroxyanisole, nordihydroguaiacetic acid, nordihydroguiaretic acid, trihydroxybutyrophenone, uric acid and its derivatives, mannose and derivatives thereof, superoxide dismutase, zinc and its derivatives (eg ZnO, ZnSO ₄ ) selenium and its derivatives (eg selenium methionine), Sti level and their derivatives (eg stilbene oxide, trans-stilbene oxide) and the According to the invention, suitable derivatives (salts, esters, ethers, sugars, nucleotides, nucleosides, peptides and lipids) of said active substances.

In addition, compounds for suppressing or alleviating skin disorders induced by UV radiation, in particular activators of peroxisome proliferator-activated receptors (PPAR activators), as described in WO 02/38150, may be added to the present invention in full Scope is referred to.

Hydrotropes such as, for example, ethanol, isopropyl alcohol, or polyols can also be used to improve the flow behavior. Polyols contemplated herein preferably have from 2 to 15 carbon atoms and at least two hydroxyl groups. The polyols may contain other functional groups, in particular amino groups, or be modified with nitrogen. Typical examples are

• glycerin;

Alkylene glycols such as ethylene glycol, diethylene glycol, propylene glycol, butylene glycol, hexylene glycol, and polyethylene glycols having an average molecular weight of 100 to 1,000 daltons;

Technical Oligoglyceringemische with an intrinsic degree of condensation of 1, 5 to 10 such as technical Diglyceringemische with a diglycerol content of 40 to 50 wt .-%;

Methyolverbindungen, in particular trimethylolethane, trimethylolpropane, trimethylolbutane, pentaerythritol and dipentaerythritol;

Lower alkyl glucosides, especially those having 1 to 8 carbons in the alkyl radical, such as, for example, methyl and butyl glucoside;

Sugar alcohols having 5 to 12 carbon atoms, such as sorbitol or mannitol,

• sugars having 5 to 12 carbon atoms, such as glucose or sucrose;

• amino sugars, such as glucamine;

• Dialcoholamines, such as diethanolamine or 2-amino-1,3-propanediol. Suitable preservatives are, for example, phenoxyethanol, formaldehyde solution, parabens, pentanediol or sorbic acid and the other classes of substances listed in Appendix 6, Part A and B of the Cosmetics Regulation. Insect repellents are N, N-diethyl-m-toluamide, 1, 2-pentanediol or ethyl Butylacetylaminopropionate in question, suitable as a self-tanner dihydroxyacetone.

As perfume oils are called mixtures of natural and synthetic fragrances. Natural fragrances are extracts of flowers (lily, lavender, roses, jasmine, neroli, ylang-ylang), stems and leaves (geranium, patchouli, petitgrain), fruits (aniseed, coriander, caraway, juniper), fruit peel (bergamot, lemon, Oranges), roots (macis, angelica, celery, cardamom, costus, iris, calmus), wood (pine, sandal, guaiac, cedar, rosewood), herbs and grasses (tarragon, lemongrass, sage, thyme), Needles and twigs (spruce, fir, pine, pines), resins and balsams (galbanum, elemi, benzoin, myrrh, olibanum, opoponax). Furthermore, animal raw materials come into question, such as civet and Castoreum. Typical synthetic fragrance compounds are ester type products, ethers, aldehydes, ketones, alcohols and hydrocarbons. Fragrance compounds of the ester type are known e.g. Benzyl acetate, phenoxyethyl isobutyrate, p-tert-butylcyclohexyl acetate, linalyl acetate, dimethylbenzylcarbinyl acetate,

Phenylethyl acetate, linalyl benzoate, benzyl formate, ethylmethylphenyl glycinate, allyl cyclohexyl propionate, styrallyl propionate and benzyl salicylate. The ethers include, for example, benzyl ethyl ether, to the aldehydes, for example, the linear alkanals having 8 to 18 carbon atoms, citral, citronellal, citronellyloxyacetaldehyde, cyclamen aldehyde, hydroxycitronellal, lilial and bourgeonal, to the ketones such as the ionone, oc-lsomethylionon and Methylcedrylketon to the alcohols Anethole, citronellol, eugenol, isoeugenol, geraniol, linalool, phenylethyl alcohol and terpineol, the hydrocarbons mainly include the terpenes and balsams. Preferably, however, mixtures of different fragrances are used, which together produce an attractive fragrance. Also essential oils of lower volatility, mostly as aroma components are used as perfume oils, eg sage oil, chamomile oil, clove oil, lemon balm oil, mint oil, cinnamon leaf oil, lime blossom oil, juniper berry oil, vetiver oil, oliban oil, galbanum oil, labolanum oil and lavandin oil. Preferably, bergamot oil, dihydromyrcenol, lilial, lyral, citronellol, phenylethyl alcohol, α-hexylcinnamaldehyde, geraniol, benzylacetone, cyclamen aldehyde, linalool, Boisambrene Forte, Ambroxan, indole, hedione, Sandelice, citron oil, tangerine oil, orange oil, Allylamylglycolat, Cyclovertal, lavandin oil, Muscat Sage oil, β-damascone, geranium oil Bourbon, cyclohexyl salicylate, Vertofix Coeur, Iso-E-Super, fixolide NP, evernyl, iraldeine gamma, phenylacetic acid, geranyl acetate, benzyl acetate, rose oxide, romilllat, irotyl and floramate alone or in mixtures.

As dyes, the substances suitable and suitable for cosmetic purposes can be used, as compiled, for example, in the publication "Cosmetic Colorants" of the Dye Commission of the Deutsche Forschungsgemeinschaft, Verlag Chemie, Weinheim, 1984, pp. 81-106. These dyes are usually used in concentrations of 0.001 to 0.1 wt .-%, based on the total mixture.

The body care compositions according to the invention also include dentifrices and, in general, oral hygiene care products (Oral Gare products).

Toothpastes contain z. Typically:

- Cleaning and polishing body such. Chalk, silicic acids, aluminum hydroxide, aluminum silicates, calcium pyrophosphate, dicalcium phosphate, insoluble sodium metaphosphate or synthetic resin powder;

Humectants, e.g. Glycerol, 1,2-propylene glycol, sorbitol, XyNt and polyethylene glycols

Binders and consistency regulators, for example natural and synthetic water-soluble polymers and water-soluble derivatives of natural substances, for example cellulose ethers, phyllosilicates, finely divided silicas (airgel-silicas, fumed silicas) Flavors, for example peppermint oil, spearmint oil, eucalyptus oil, aniseed oil, fennel oil, caraway oil, menthyl acetate, cinnamaldehyde, anethole, vanillin, thymol and mixtures of these and other natural and synthetic flavors

Sweeteners, e.g. Saccharin sodium, sodium cyclamate, aspartame, acesulfan K, stevioside, monellin, glycyrrhicin, dulcine, lactose, maltose or fructose

Preservatives and antimicrobials, e.g. p-hydroxybenzoic acid esters, sodium sorbate, triclosan, hexachlorophene, phenylsalicylic acid ethers, thymol, etc.

Pigments such as e.g. Titanium dioxide or pigment dyes for producing colored stripes

- buffer substances e.g. primary, secondary or tertiary alkali phosphates, citric acid / Na citrate

wound healing and anti-inflammatory agents, e.g. Allantoin, urea, azulene, panthenol, acetylsalicylic acid derivatives, plant extracts, vitamins, e.g. Retinol or tocopherol.

The total amount of auxiliaries and additives may be 1 to 50, preferably 5 to 40 wt .-% - based on the means - amount. The preparation of the cosmetics and personal care products can be carried out by conventional cold or hot processes; It is preferable to work according to the phase inversion temperature method.

The following examples describe the invention without, however, limiting it to:

example 1

In in vitro models with a keratinocyte line (HaCaT), both basal and induced release of pro-inflammatory cytokines can be measured. In Examples 1a to 1d, the influence of ODN on basal IL8 secretion of HaCaT cells was investigated. The cells were incubated for 18 to 20 hours in culture medium (Hanks' basal medium with 5% fetal calf serum, 2 mM Glutamax I from Gibco ™ and 100 U / ml penicillin / streptomycin) with the indicated ODN (final concentration 4 μM) or without (control). The cell supernatants were briefly centrifuged off and the IL8 concentration determined by ELISA. Subsequently, relative IL8 secretion (ratio to control) was calculated. For each experiment, the IL8 values of at least three samples were determined and each experiment performed at least three times. Indicated are the mean values from the independent experiments and the corresponding standard deviations. Statistical significance of differences (unless otherwise specified from sample to control) was determined by Student's t-test, the corresponding p-values are given.

Example 1a (comparative example with CpG):

As can be seen in Figure 1, a typical member of the CpG-A ODN (1585 (A)), in contrast to ODN, leads to the CpG classes B (2084 (B)) and C (M362 (C)) in particular marked decrease in the basal Il_8 level of HaCaT keratinocytes. The inhibition is comparable to that of 20G-PTO (poly-G, 20mer, PTO backbone) and significantly stronger than that of 20C-PTO (poly-C, 20mer, PTO backbone). The anti-inflammatory effect is not dependent on the CpG motif, since the GpC control (2118 (KonA)) shows a similarly strong effect.

In general, CpG A ODN, like the corresponding GpC control, has a chimeric backbone that contains only phosphorothioate linkages at the ends. They have a palindromic sequence in which the CpG motif is embedded in the case of the CpG A ODN and a stem-loop structure can be trained. Probably for steric reasons, phosphodiester linkages in the area of the postulated stem-loop structure are important for optimal effect. In addition, at the 5 'and 3' ends, they show consequences of guanines. Figure 2 shows predicted structures of ODN 2118 (KonA).

Example 1b

Using the example of 2118 (KonA), the influence of the parameters stem-loop structure, phosphorothioate / phosphodiester distribution in the backbone, and length and number of guanine sequences were investigated. As shown in Figure 3, altering the stem-loop structure while retaining the guanine sequences and the corresponding phosphorothioate / phosphodiester linkages has little effect on the anti-inflammatory effect of the oligonucleotides. A change in the base composition of the loop (2118-11) or an extension of the "stem" structure from three to five base pairs (2118-13) as well as an extension of the loop from four to seven bases (2118-12) leads only to minor ones Alterations in the reduction of the basal IL8 level of HaCaT cells Even a strong change in the sequence of 2118 while retaining a stem-loop structure (2118 (KonA) -P) has little effect, but it is noteworthy that the replacement of the Stem-loop structure by a thymine sequence (SS-126) leads to a strong loss of anti-inflammatory potential, which illustrates the importance of this secondary structure for the efficacy of these oligonucleotides.

Example 1c

The position of the phosphorothioate and phosphodiester linkages is also important for the effect of this ODN class. As can be seen in Figure 4, an ODN of the same sequence, which also has loopwise connections to the phosphorothioate linkages of 2118 (KonA) (2118-1), leads to a smaller decrease in the basal IL8 level of HaCaT cells as 2118 (KonA). The same applies to an ODN which, for the same sequence, only phosphorothioate Contains links (2118 (KonA) -PTO). However, altering the PTO / PDE distribution such that phosphodiester linkages are present in the postulated loop and the remainder of the molecule still has phosphorothioate linkages (2118-2) gives the same effect as in 2118 (KonA).

Phosphorothioate linkages around the loop are said to be detrimental to the formation of the stem-loop structure due to lack of flexibility. The formation of the stem-loop structure at 2118-1 and 2118 (KonA) -PTO could thus be hindered by the phosphorothioate linkages. Since this obviously leads to a loss of effect, it underlines the importance of the stem-loop structure for the optimal effect of this ODN group. The secondary structure could be beneficial in bringing together the guanine sequences at the 5 'and 3' ends of the ODN.

An ODN derived from 2118 (KonA), which consists only of phosphodiester linkages, shows a markedly reduced effect in terms of lowering the basal IL8 level of HaCaT keratinocytes (2118 (KonA) -PDE). This could be due to the known lower stability of phosphodiesters compared to phosphorothioates or phosphodiester / phosphorothioate mixers.

Example 1d

Other important parameters for the anti-inflammatory effect of this ODN group are the number and length of guanine sequences at the 5 'and 3' ends. The ODNs tested to determine these parameters are all derived from 2118 (KonA). Sequence changes are limited to the guanine sequences at the ends, with one or more guanines usually replaced by adenines and / or thymines. The distribution of phosphorothioate and phosphodiester linkages in the ODN remained unchanged, as was the length of the ODN. For better orientation, the number of guanines is included in parentheses when naming the molecules. 2118 (KonA) has four guanines at the 5 'end and six guanines at the 3' end. For example, in 2118- (4-O) all guanines at the 3 'end were replaced by tymines and adenines, the four guanines at the 5 'end remained unchanged, which is reflected in the designation "(4-0)." This applies to all the experiments shown in Figures 5 to 10.

As can be seen in Figure 5, the omission of either guanine sequence at the 3 'or 5' ends results in loss of effect, regardless of which bases are used as a replacement. The drop in efficiency is particularly dramatic when the sequence of six guanines at the 3 'end is removed. The omission of the four guanines at the δ 'end has less severe effects on the anti-inflammatory effect. Not only the difference in length of the two guanine sequences is decisive for this difference, but also their position at the 5 'or 3' end. If the consequences are at the 3 'end, the ODNs lead to a greater reduction in the basal IL8 level of the HaCaT keratinocytes than if the same consequences are found at the 5' end (Figure 6).

In addition to the location and the presence of one or two guanine sequences, the length of the corresponding sequences is of great importance for the anti-inflammatory potential of this ODN group. If one shortens the four-guanine sequence at the 5'-end of 2118 (KonA) by one guanine, this only leads to a slight loss of effect. However, any further truncation leads to a sharp increase in the basal IL8 level of HaCaT keratinocytes and thus to a significant loss of ODN, regardless of whether two, one or no guanine remain at the 5'-end (Figure 7).

If the sequence consisting of six guanines is shortened at the 3'-end of 2118 (KonA), an increasing loss of ODN results with increasing shortening. Particularly striking is the difference between a four-guanine sequence at the 3'-end (2118- (4-4)) and one consisting of three guanines (2118- (4-3)). A further shortening of the sequence to two or less guanine leads to no further significant deterioration of the effect (Figure 8). Shortening both the six-guanine sequence at the 3'-end and the four-guanine sequence at the 5'-end of 2118 (KonA) simultaneously show a similar picture as in the experiments described above. With increasing shortening of the consequences, an increasing loss of effect of the ODN occurs. This is particularly noticeable when both episodes consist of only three guanines (2118- (3-3)). Further shortening will then result in no additional deterioration of the anti-inflammatory potential. However, these ODNs only lead to a slight decrease in the basal IL8 level of the HaCaT cells (Fig. 9).

The derivatives of Figure 9 derived from 2118 (KonA) are asymmetric molecules. Like 2118 (KonA) (see Fig. 2), they have different numbers of bases on the two sides of this structure outside the stem-loop structure, namely four to five on the 5 'side and six to seven on the 3' side. Side of the secondary structure. As a result, the guanines and guanine sequences are not directly opposite each other in 2118- (4-4), 2118- (3-3), 2118- (2-2) and 2118- (1-1). In order to investigate the influence of this asymmetry on the biological effect, ODNs were tested which are completely symmetrical and compared with the asymmetric ODN of Fig. 9. In Figure 10 it can be clearly seen that, with the exception of one ODN pair, the asymmetrically constructed ODNs always have the stronger anti-inflammatory effect and the symmetrical ODNs are generally only very weakly or not at all effective. Since the corresponding pairs differ not only in the symmetry but also in the sequence, influences due to the sequence differences can not be ruled out. However, they are rather unlikely, since all previous experiments show no particular sequence specificity. An asymmetric structure of the ODN, in which the guanine sequences are not directly opposite, thus does not seem to be a disadvantage for the anti-inflammatory effect, but may even be an advantage.

With the oligonucleotides described above, a group could be identified which has a particularly high anti-inflammatory potential distinguished against skin cells. The group is essentially characterized by three parameters: 1) a sequence segment, via which the formation of a stem-loop secondary structure is possible (by being able to fold back on itself or having mirror-symmetric sequences of bases, also as a palindromic sequence segment 2) one or more guanine sequences to one or both sides of the stem-loop structure and 3) phosphodiester linkages in the region of the loop structure, phosphorothioate linkages at least at both ends. Parameter 3) is necessary for an optimal effect, but does not have the same significance as 1) and 2).

ODN table

ODN table:

5 'and 3' end of the oligonucleotides are labeled, phosphorothioate linkages are indicated by *. Phosphodiester linkages are not extra labeled. The effect is classified into five categories after reduction of the basal IL8 level of HaCaT keratinocytes: no reduction or reduction to> 90% of baseline level: -; Reduction to values between 75% and 90%: +; Reduction to values between 50% and 74%: ++; Reduction to values between 25% and 49%: +++; Reduction to values <25%: ++++; The ability to form a stem-loop structure was calculated using the mfold 3.1 program

(Http://www.bioinfo.rpi.edu/applications/mfold/old/dna/form1.cgi). Sequences were entered as a linear DNA and the folding at 37 ⁰ C and in the presence of 15OmM Na ⁺ and 0.5 mM Mg ⁺⁺ by using the calculated correction oligomer function. Phosphorothioate linkages were not included in the calculation. The number, position and length of guanine sequences are given. The guanine sequence refers to those that contain at least two consecutive guanines. Terminal single guanine are also indicated. List of pictures:

Fig. 1: Influence of different CpG ODN and their GpC controls on the basal IL8 level of HaCaT keratinocytes.

A CpG-A ODN and the corresponding GpC control lead to a similar reduction in IL8 basal level as a poly-G-ODN (20G-PTO, 20mer, PTO backbone). Shown in each case is a representative of the three CpG classes. The class is indicated in brackets after the number of the ODN: (A) for CpG-A, (B) for CpG-B, and (C) for CpG-C. The designation (KonA) and (KonB) stands for the corresponding GpC control. 20C-PTO is a poly-C-ODN (20mer, PTO backbone). The exact sequences of the ODN can be found in the ODN table.

Fig. 2: Possible secondary structures of 2118 (KonA).

The shown secondary structures were calculated using the program mfold 3.1 http://www.bioinfo.rpi.edu/applications/mfold/old/dna/form1.cgi. The 5 'end is indicated by a dot. The sequence was entered as linear DNA and the folding was calculated at 37 ° C and in the presence of 15 mM Na ⁺ and 0.5 mM Mg ⁺⁺ using the oligomer correction function. Phosphorothioate linkages (marked with *) were not included in the calculation. The loop contains the GpC dinucleotide, which in the case of 1585 (A) is replaced by a CpG dinucleotide.

Fig. 3:

(A) Influence of the 2118 (KonA) stem-loop structure on the suppression of the basal IL8 level of HaCaT keratinocytes.

The formation of a stem-loop structure is essential for optimum performance of this ODN class. The exact sequences of the ODN can be found in the ODN table.

(B) Possible secondary structures of the oligonucleotides. The secondary structures shown were calculated using the program mfold 3.1 (http://www.bioinfo.rpi.edu/applications/mfold/old/dna/form1.cgi). The 5 'end is indicated by a dot. Sequences were entered as linear DNA, and calculates the convolution at 37 ⁰ C and in the presence of 15OmM Na ⁺ and 0.5 mM Mg ⁺⁺ using the oligomer-correction function. Phosphorothioate linkages (marked with *) were not included in the calculation.

Fig. 4: Influence of distribution and content of phosphodiester and phosphorothioate linkages in 2118 (KonA) on the basal IL8 level of HaCaT keratinocytes.

For optimal effect, the postulated loop of 2118 (KonA) phosphodiester linkages must be included and the ends protected by phosphorothioate linkages. The exact sequences of the oligonucleotides can be found in the ODN table.

Fig. 5: Influence of guanine sequences of 2118 (KonA) on the basal IL8 level of HaCaT keratinocytes. The omission of one of the two guanine sequences at the 3'- or 5'-end leads to a loss of effect. At 2118-6 (0-6), the guanine sequence was replaced at the 5 'end by a cytosine sequence and in 2118-7 (0-6) by alternating adenines and thymines. Replacement of the guanine sequence at the 5 'end by alternating thymines and adenines (2118- (4-O) results in the greatest loss of effect.) The exact sequences of the oligonucleotides can be found in the ODN table.

Fig. 6: Influence of the location of the guanine sequences of 2118 (KonA) on the basal IL8 level of HaCaT keratinocytes.

If a guanine sequence of 2118 (KonA) is deleted, the basal IL8 level of HaCaT cells is decreased the most when the remaining sequence is at the 3 'end. The exact sequences of the oligonucleotides can be found in the ODN table. Fig. 7: Influence of the length of the guanine sequence at the 5 'end of 2118 (KonA) on the basal IL8 level of HaCaT keratinocytes.

A shortening of the guanine sequence at the 5'-end of 2118 (KonA) leads to a reduction of the repressive influence of ODN on the basal IL8 level of HaCaT cells. The effect is particularly evident in less than three guanines. The exact sequences of the ODN can be found in the ODN table.

Fig. 8: Influence of the length of the guanine sequence at the 3 'end of 2118 (KonA) on the basal IL8 level of HaCaT keratinocytes.

A shortening of the guanine sequence at the 3 'end of 2118 (KonA) leads to a reduction of the repressive influence of ODN on the basal IL8 level of HaCaT cells. The effect is particularly evident in less than four guanines. The exact sequences of the ODN can be found in the ODN table.

Fig. 9: Influence of the length of both guanine sequences (at the 3 'and 5' ends) of 2118 (KonA) on the basal IL8 level of HaCaT keratinocytes.

A shortening of both guanine sequences of 2118 (KonA) leads to a reduction of the repressive influence of ODN on the basal IL8 level of HaCaT cells. The effect is particularly evident with less than four guanines in both sequences. The exact sequences of the ODN can be found in the ODN table.

Fig. 10: Influence of symmetry of Stem-loop-forming ODN with guanine sequences on the basal IL8 level of HaCaT keratinocytes.

Symmetric ODNs (SS-127 (4-4), SS-128 (3-3), SS-129 (2-2), and SS-130 (1-1)) result in lower basal IL8 Levels of HaCaT cells as the 2118 (KonA) -derived ODN with the same number, location, and length of guanine sequences. The exact sequences of the ODN can be found in the ODN table. Right: Possible secondary structures of two ODN, which are the show different symmetry of these two ODN groups. The shown stem-loop structures were calculated using the program mfold 3.1 (http://www.bioinfo.rpi.edu/applications/mfold/old/dna/form1.cgi). The 5 'end is indicated by a dot. Sequences were entered as linear DNA, and calculates the convolution at 37 ⁰ C and in the presence of 15OmM Na ⁺ and 0.5 mM Mg ⁺⁺ using the oligomer-correction function. Phosphorothioate linkages (marked with *) were not included in the calculation.

Claims

claims:

1. Cosmetic or pharmaceutical preparation for the prophylaxis and / or treatment of epithelial covering tissue, characterized in that it contains nucleic acids without CpG motif, which comprise sequences suitable for the formation of stem-loop secondary structures.

2. Preparation according to claim 1, characterized in that the nucleic acids without CpG motif, which comprise sequences suitable for the formation of stem-loop secondary structures, at the 5'- and / or at the 3-end of the star C, G or L-rich sequences containing from C, G or I in the range of 25% to 100%, preferably 50% to 100%, more preferably 75% to 100% and most preferably 100%.

3. Preparation according to one of the preceding claims, characterized in that the length of the C-, G- or L-rich, preferably G-rich sequences in the range of 2 to 12 nucleotides, in particular in the range of 2 to 10 nucleotides, preferably in Range of 2 to 8 nucleotides, more preferably in the range of 2 to 6 nucleotides, and most preferably in the range of 4 to 6 nucleotides.

4. Preparation according to one of the preceding claims, characterized in that the C-, G- or L-rich, preferably G-rich sequences are arranged only on one side of the star, in particular at the 3 'end.

5. Preparation according to one of claims 1 to 3, characterized in that the C-, G- or L-rich, preferably G-rich sequences on both sides of the star are arranged symmetrically or preferably asymmetrically.

6. Preparation according to one of the preceding claims, characterized in that the C, G or L-rich sequences are selected under poly-1-homopolymers, poly-C-homopolymers or poly-G-homopolymers, preferably poly-G-homopolymers.

7. Preparation according to one of claims 1 to 3 and 5 to 6, characterized in that on each side of the star 4 guanines at the 5'- end of the star and 6 guanine at the 3'-end of the star are arranged.

8. Preparation according to one of the preceding claims, characterized in that the nucleic acids without CpG motif, which comprise sequences suitable for the formation of stem-loop secondary structures, are selected from sequences with the Seq. IDs 1 to 31.

9. Preparation according to one of the preceding claims for the prophylaxis and / or treatment of inflammatory epithelial cover tissue.

10. A preparation according to any one of the preceding claims for the prophylaxis and / or treatment of inflammatory changes selected from chronic or acute inflammations, especially exudative inflammation, serous inflammation, fibrinous inflammation, purulent inflammation, hemorrhagic inflammation, necrotizing and ulcerating inflammations, gangrenous Inflammation and acute lymphocytic inflammation.

11. A preparation according to any one of the preceding claims for the prophylaxis and / or treatment of inflammatory changes caused by noxious or stressors selected from: a) biological noxae or stressors, especially pathogens, autoimmune reactions, TNF, b) chemical noxae or Stressors, in particular poisons, irritants and c) physical noxae or stressors, in particular UV radiation, osmotic changes, mechanical stress, heat stress.

12. Preparation according to one of the preceding claims for the prophylaxis and / or treatment of inflammatory changes selected from inflammatory aging processes, psoriasis, atopic eczema, seborrheic dermatitis, scleroderma, 'dry skin', alopecia arreata, vitiligo, bullous disorders, lupus erythematosus, rejection reactions (graft-versus-host reactions), radiation-related, in particular UV-related skin inflammations, toxic contact dermatitis, mucosal irritation and inflammation, in particular nasal irritation and vulvovaginitis, angular cornering of the mouth and functional disorders of the epidermal barrier.

13. Preparation according to one of the preceding claims for the prophylaxis and / or treatment of inflammatory changes which are selected from Th2-mediated diseases, in particular diseases of the atopic form, in particular selected from hay fever, atopic dermatitis (atopic dermatitis, atopic eczema), exogenous allergic bronchial asthma , allergic enteritis, allergic

Conjunctivitis, hives and other allergic skin diseases.

14. Preparation according to one of the preceding claims, characterized in that the nucleic acids without CpG motif, which comprise suitable sequences for the formation of stem-loop secondary structures, a length of 10 to 100, in particular 10 to 40, preferably 10 to 30, preferably 13 to 27 and most preferably from 16 to 24 nucleotides.

15. Preparation according to one of the preceding claims, characterized in that the nucleic acids without CpG motif, which comprise sequences suitable for the formation of stem-loop secondary structures, are completely or partially chemically modified.

16. Preparation according to claim 15, characterized in that the chemical modification is selected from a) modification of the internucleoside bridges, in particular exchange of phosphodiestems for methylphosphonates, phosphoramidates, phosphorothioates or hydroxylamines; b) modification of the sugar components, in particular exchange of the ribose for various hexo- or pentopyranoses or 3'-5'-carbocyclic bridged derivatives of 2'-deoxyribose; or c) exchange of the strand backbone, in particular replacement of the polyester chains based on sugar-phosphate units against carboxamide chains based on amino acid derivatives, such as N- (2-aminoethyl) -glycine units, wherein the exchange of phosphodiestems for phosphorothioates mentioned under a) is particularly preferred.

17. Preparation according to claim 15 or 16, characterized in that the nucleic acids without CpG motif, which comprise sequences suitable for the formation of stem-loop secondary structures, have phosphorothioate phosphodiester mixmere.

18. Preparation according to one of the preceding claims, characterized in that it is applied topically to the epithelial covering tissue.

19. Preparation according to one of the preceding claims, characterized in that it contains the nucleic acids without CpG motif, which comprise sequences suitable for the formation of stem-loop secondary structures, packaged in liposomes.

2O.Wascheweichspüler, hand washing, body and hair care products, hair dyes or hand dishwashing detergents, comprising nucleic acids without CpG motif, which comprise sequences suitable for the formation of stem-loop secondary structures, as described in claims 1 to 17.