DE10361502A1 - Cosmetic or pharmaceutical preparations containing superstructure-forming nucleic acid sequences - Google Patents

Abstract

The present invention relates to cosmetic or pharmaceutical preparations for the prophylaxis and / or treatment of epithelial cover tissue containing superstructure-forming nucleic acid sequences, the use of such superstructure-forming nucleic acid sequences for the prophylaxis and / or treatment of epithelial cover tissue, and laundry softeners, hand detergents, personal care products. and hair care products, hair dyes or hand dishwashing detergents containing such superstructure-forming nucleic acid sequences.

Description

The The present invention relates to cosmetic or pharmaceutical Preparations for the prophylaxis and / or treatment of epithelial covering tissue, contain the superstructure-forming nucleic acid sequences that Use of such superstructure-forming nucleic acid sequences for the prophylaxis and / or treatment of epithelial covering tissue as well Laundry softener, hand detergent, body and Hair care products, hair dye or hand dishwashing detergent, containing such superstructure-forming nucleic acid sequences.

Hints for immunostimulatory Effects of "foreign" DNA already exist since the 1960's (Jensen KE, Neal AL, Owens RE, Warren J: Interferon Responses of Chick Embryo Fibroblasts to Nucleic Acids and Related Compounds. Nature; 200: 433-434, 1963). Described was both the induction of the production of Interferon gamma, as well as the activation of natural Killer cells and induction of antitumoral activity by fractions of Bacillus Calmette-Guerin (BCG) (Tokunaga T, Yamamoto H, Shimada S, Abe H, Fukuda T, Fujisawa Y, Furutani Y, Yano O, Kataoka T, Sudo T, Makiguchi N, Suganuma T: Antitumor Activity of Deoxyribonucleic Acid Fraction From Mycobacterium Bovis BCG. I. Isolation, Physicochemical Characterization and Antitumor Activity. J Natl Cancer Res; 72: 955-962, 1984). The immunostimulant activity of this Fraction could by pre-incubation with DNAsen, but not RNAses destroyed become. This suggested the conclusion that the bacterial DNA is the immunostimulating part of the BCG fraction accounts. Exact investigation of the immunologically active DNA sequences revealed that these are oligonucleotides consisting of a central palindrome with a CpG motif exist.

Further Investigations gave rise to the Hypothesis that this is for the immunostimulatory effect important motif from a central CpG group composed at the 5'-end from two purines and at the 3'-end flanked by two pyrimidines (War AM, Yi A, Matson S, Waldschmidt TJ, Bishop GA, Teasdale R, Koretzky GA, Klinman DM: CpG Motifs in Bacterial DNA Trigger direct B-Cell Activation. Nature; 374: 546-549, 1995). DNA sequences with the consensus sequence 5'-A / GA / GCGCT / TC / T-3 'are referred to as CpG. CpG dinucleotides are suppressed in eukaryotic DNA.

On the one hand These motifs in eukaryotic DNA come only with a fifth of the expected frequency, on the other hand, they are methylated to 60-90% (Bird AP: CpG-rich Islands and the Function of DNA Methylation. Nature; 321: 209-213, 1986). In contrast, the CpG motif is found in bacterial DNA unmethylated and with the expected frequency (1:16). It could be shown that methylation has the stimulatory potential of the CpG motif destroyed (War, see above). These differences between bacterial and eukaryotic DNA it, the biological observations concerning the immunostimulatory Effect of bacterial DNA and synthetic CpG oligodeoxynucleotides Meaningfully interpret (ODN).

The Detection of "foreign" DNA and the on it The following immunological reaction is for the innate immune system a possibility to distinguish between "self" and "foreign", without mediation and intervention of the adaptive immune system to be instructed.

The Effects and the mechanism of action of CpG ODN were mainly examined in the murine system. ODN affects both the innate as well also stimulatory to the adaptive immune system of the mouse, wherein the effects differ with respect to signal transmission and sequence specificity.

It For example, CpG ODN could be shown to be different Presenting types of antigen Cells (APZ) have an immunostimulatory effect. The stimulation of purified B lymphocytes with unmethylated CpG ODN leads to Proliferation and secretion of immunoglobulins (Krieg, supra). CpG ODNs induce activation of the transcription factor in macrophages Nuclear Factor kB (NF-kB), the transcription of cytokine mRNA and the secretion of cytokines such as TNFa, IL-1, IL-6 and IL-12 (Sparwasser T, Miethke T, Lipford GB: Macrophages Sense Pathogens via DNA Motifs: Induction of Tumor Necrosis Factor Alpha Mediated Shock. Eur J Immunol; 27: 1671-1679, 1997).

CpG ODN affect both mature and immature dendritic cells activating. You reinforce on both cell populations MHC II expression and expression of costimulatory molecules (CD40, CD86) and induce the production of cytokines such as IL-6, IL-12 and TNFa. To further investigate the mechanism of action of CpG ODN, experiments were performed with immobilized CpG ODN. The Results of these experiments indicate that a recording the CpG ODN into the cell for the immunostimulatory effect is necessary (Krieg, see above).

Other experiments show that the uptake of DNA at the cell surface of macrophages can be blocked by any competitively added ODN (Haecker H, Mischak H, Mieth ke T, Liptary S, Schmid R, Sparwasser T, Heeg K, Lipford GB, Wagner H: CpG DNA Specific Activation of Antigen Presenting Cells Requires Stress Kinase Activity and Is Preceded by Non-Specific Endocytosis and Endosomal Maturation. EMBO Journal; 17: 6230-6240, 1998), suggesting that uptake of ODN into the cell is not sequence specific. In contrast, CpG specificity could be mediated by an intracellular receptor located, for example, in the endosome.

The Hypothesis of endosomal localization of an intracellular CpG receptor is underpinned by results that show that the endosomal acidification for the Signal path of the CpG ODN is necessary because the CpG ODN effect by Inhibitors of endosomal acidification such as. Chloroquine is blocked (Häcker, see above).

Of the full However, the mechanism of action and pathway of the CpG ODN is largely still unclear. CpG ODNs exert their effect on macrophages and dendritic cells Cells directly while the CpG ODN effect on B cells both directly and in the sense a costimulation possible is (war, see above). In contrast, direct effects of CpG ODN not shown on T cells. However, T cells that have one T cell receptor ligation get its signal 1, costimulated by CpG ODN (Bendigs S, Salzer U, Lipford GB, Wagner H, Heeg K: CpG Oligodeoxynucleotides Co-Stimulate Primary T Cells in the Absence of Antigen Presenting Cells. EUR. J Immunol; 29: 1209-1218, 1999).

These Results suggest that the mechanism of T cell stimulation another is that of a direct CpG ODN effect on APZ. The Studies of the direct effect of ODN on T cells were performed in vitro. However, there are many in vivo results in which CpG ODN as an adjuvant, and by the injection of CpG ODN T cell activation was induced in vivo. The CpG ODNs support the Formation of a TH1 immune response and induce a strong peptide-specific cytotoxic T lymphocyte activity (CTL).

in the Unlike the murine system, the effects of ODN in the human System only a few findings before. It is known that ODN with CpG motifs induce the production of IFNa in peripheral blood lymphocytes. Furthermore, it is shown that by CpG ODN - similar to the murine system - natural killer cells through the mediation of IL-12 produced by activated macrophages will be activated (Ballas ZK, Rasmussen WL, War AM: Induction of NK Activity in Murine and Human Cells by CpG Motifs in Oligodeoxynucleotides and bacterial DNA. J Immunol; 157: 1840 -1845, 1996). Humane peripheral mononuclear Cells (peripheral blood monocytic cells = PBMZ) are replaced by CpG ODN sequence-specific activated.

These Activation leads to an increased Expression of CD86, CD40, MHC I and MHC II molecules and to production of the cytokines IL-12, IL-6 and TNFa. Like in murine system, CpG ODN induce the proliferation of human B cells (Bauer M, Heeg K, Wagner H, Lipford GB: DNA Activates Human Immune Cells through a CpG Sequence Dependent Manner. Immunology; 97: 699-705, 1999). The Hitherto obtained results in the human system have many similarities with the results in the murine system.

CpG Therefore, in the prior art, an immunoprotective and immunostimulating Impact attributed and in this sense they are - currently still experimental - used.

Next Oligonucleotides (ODN) containing CpG motifs have been more recently It can also be shown that ODNs that do not contain CpG also have an immunostimulating effect To be effective. These ODNs are referred to in the literature as non-CpG. The quality of the immune stimulation but can differ between CpG and non-CpG. So could shown that CpG cause a Th1 response in immune cells, while non-CpG induce a Th2 phenotype (Sano K, Shirota H, Terui T, Hattori T, Tamura G: Oligodeoxynucleotides without CpG Motifs work as adjuvant for the induction of Th2 differentiation in a sequence-independent manner. J Immunol; 170: 2367-2373, 2003). In this context, an amplification of the antigen-induced Activation of T helper cells and Th2 differentiation of naive T cells to be watched. These results are in line with works by McCluskie and Davis (McCluskie MJ, Davis HL: Oral, Intrarectal and Intranasal immunizations using CpG and non-CpG oligodeoxynucleotides as adjuvants. Vaccine; 19 (4-5): 413-422, 2000), in the mouse model a Th2-directed have found immunostimulatory effect of non-CpG by CpG can be moved back towards a Th1 response.

While at The effect of CpG TLR-9 seems to play an important role and co-localized with the CpG, this is likely in the case of non-CpG not the case (Bauer S, Kirschning CJ, Hacker H, Redecke V, Hausmann S, Akira S, Wagner H, Lipford GB: Human TLR9 confers responsiveness to bacterial DNA via species-specific CpG motif recognition. Proc Natl Acad Sci USA; 98 (16): 9237-9242, 2001).

The non-CpG has been mainly attributed an immunostimulatory role. however Immunosuppressive effects of non-CpG were also found. For example, an inhibitory motif (CCT block near the 5'-end, GGG (G) block near the 3'-end, linker 3-5 nucleotides) could be identified, which interferes with the stimulation of murine spleen cells by certain CpG motifs (Lenert P, Rasmussen W, Ashman RF, Ballas ZK: Structural characterization of the inhibitory DNA motif for type A (D) -CpG-induced cytokine secretion and NK-cell lytic activity in mouse spleen cells. "DNA and Cell Biol; 22 (10) : 621-631, 2003).

in the Mouse model could be shown that inhibitory phosphorothioate ODN the manifestation and reduce severe CpG-induced arthritis by up to 80% (Zeuner RA, Ishii KJ, Lizak MJ, Gursel I, Yamada H, Klinman DM, Verthelyi D: Reduction of CpG-induced arthritis by suppressive oligodeoxynucleotides. Arthritis Rheumatism; 46 (8): 2219-2224, 2002).

One suppressive effect of non-CpG on the immune system of the skin so far, however, not known.

at the search for particularly effective immunosuppressive nucleotide sequences has the applicant first looking for sequence-specific similarities and motifs, the could characterize immunosuppressive non-CpG. Surprisingly, however found that not sequence but structure-specific functional principles immunosuppressive non-CpG characterize when topically applied to the skin exert an immunosuppressive effect. For other systems, however, these principles are not or likely not the effective motive dar.

inflammation der Hautorgans are widespread diseases that are both endogenous as well as being triggered exogenously. To be treated mostly topically or systemically administered steroid-based therapeutics. This substance class shows in addition to their effectiveness and a number of unwanted Side effects (e.g., skin atrophy, Cushing syndrome). An alternative Principle for the treatment of inflammation the skin is therefore desirable.

object The present invention is therefore 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 altered epithelial Covering tissue, which is characterized by being superstructure-forming Nucleic acid sequences, especially G-quadruplex, frayed Wire- or i-motif-forming DNA sequences contains.

The inventive preparation The superstructure-forming nucleic acid sequences can also be used in combination with other suitable, especially anti-inflammatory agents (eg corticosteroids).

Under Superstructure-forming nucleic acid sequences are nucleic acids to understand that empowers are non-covalent bonds to other nucleic acids superstructures, in particular G-quadruplexes, so-called "Frayed Wires" or "i-motifs" form. Preferably include usable according to the invention Superstructure-forming nucleic acid sequences C, G or I rich Sequences containing C, G or I in the range of 25 % to 100%, preferably 50% to 100%, especially preferred 75% up to 100% and most preferably 100% in very particular Dimensions are preferred poly-I-homopolymers, poly-C-homopolymers or poly-G-homopolymers. Where C stands for Cytosine, G for Guanin and I for Inosine.

The in the below Examples presented results suggest that the effect of non-CpG is dependent on the guanine, cytosine or hypoxanthine content. Since random polymers are also effective, the effect does not seem to be dependent on a defined sequence. Especially effective are C-, G- and I-rich ODNs (I-rich means inosine-rich. inosine is the hypoxanthine-containing nucleoside). These ODN are particular suitable for forming DNA superstructures. The formation of such ODN superstructures is primarily dependent from the base composition of the ODN. Of further importance in the Formation of ODN superstructures are the pH, the ionic strength, the Temperature and the presence of certain cations.

Guanosine-rich and inosine-rich ODNs can form G-quartets via Hoogsteen base pairings, which "stacked together" lead to the formation of G-quadruplexes, which constitute a multimer consisting of four single-stranded DNAs. The formation can be intermolecular and intramolecular Thus, it is important that the ODN contain several consecutive guanines (Stefl R, Spackova N, Berger I, Koca J, Sponer J: Molecular Dynamics of DNA Quadruplex Molecules containing Inosine, 6- thioguanine and 6-thiopurine Biophys J, 80: 455-468, 2001; Keniry MA: Quadruplex structures in nucleic acids Biopolymers; 56: 123-146, 2001; Shafer RH & Smirnov I: Biological aspects of DNA / RNA quadruplexes. Biopolymers; 56: 209-227, 2001) G-quadruplexes can be formed from both phosphodiester and phosphorothioate (Dapic V, Bates PJ, Trent JO, Rodger A, Thomas SD, Miller DM: Antiproliferative activity of G-quartet). f orming oligonucleotides with backbone and sugar modifications. Biochemistry, 41: 3676-3685, 2002).

It it is likely that G-quadruplexes occur naturally in the cell and of biological importance (Shafer RH & Smirnov I: Biological aspects of DNA / RNA quadruplexes. biopolymer; 56: 209-227, 2001).

So is e.g. suspected that the telomeres of chromosomes have such structures can train (Phan AT & Mergny JL: Human telomeric DNA: G-quadruplex, i-motif and Watson-Crick double helix. Nucleic Acid Res, 30 (21): 4618-4625, 2002).

moreover anti-proliferative effects of G-quadruplex-forming ODN have been described (Bates PJ, Kahlon JB, Thomas SD, Trent JO, Miller DM: Antiproliferative activity of G-rich oligonucleotides correlates with protein binding. J Biol Chem, 274 (37): 26369-26377, 1999), as well as some aptamers that form such structures and antiviral (Suzuki J, Miyano-Kurosaki N, Kuwasaki T, Takeuchi H, Kawai G, Takaku H: Inhibition of human immunodeficiency virus type 1 activity in vitro by a new self-stabilized oligonucleotide with guanosine thymidine quadruplex motifs. J Virol, 76 (6): 3015-3022, 2002) or thrombin-binding act (Bock LC, Griffin LC, Latham JA, Vermaa's EH, Toole JJ: Selection of single-stranded DNA molecules that bind and inhibit human thrombin. Nature, 355: 564-566, 1992). Furthermore Many proteins have been described that bind G-quadruplexes can. About their Function with regard to these structures still largely prevails Uncertainty (Shafer RH & Smirnov I: Biological aspects of DNA / RNA quadruplexes. biopolymer; 56: 209-227, 2001). An anti-inflammatory effect has not been described.

Next G-quadruplexes can Many G-rich Oligos also train so-called "Frayed Wires" are u.a. longer G-sequences in ODN necessary. These structures are about them G sequences for the aggregation of ODN involving a large number of single strands could be (Poon K & MacGregor RB Jr: Formation and structural determinants of multi-stranded guanine-rich DNA complexes. Biophys Chem, 84: 205-216, 2000).

C-rich oligonucleotides can form relatively stable so-called "i-motifs" in the neutral and above all in the slightly acidic pH range, provided that several sequences of at least two consecutive cytosines are involved in the protonation of one cytosine. protonated cytosine are formed ( 9 ).

As well As with G-quadruplexes, there are proteins in i-motifs as well can bind these structures (Shafer RH & Smirnov I: Biological aspects of DNA / RNA quadruplexes. biopolymer; 56: 209-227, 2001). Also, poly-C-ODN with a length attributed an antiviral activity of more than 20 bases (Majumdar C, Stein CA, Cohen JS, Broder S, Wilson SH: Stepwise mechanism of HIV reverse transcriptase: primer function of phosphorothioate oligodeoxynucleotide. Biochemistry; 28: 1340-1346, 1989).

I motifs can formed by both phosphodiesters and phosphorothioates (Kanehara H, Mizuguchi M, Tajima K, Kanaori K, Makino K: Spectroscopic evidence for the formation of four-stranded solution structure of oligodeoxycytidine phosphorothioate. Biochemistry; 36: 1790-1797, 1997). Generally, over i motifs less well known than about G-quadruplexes. An anti-inflammatory effect was also found for i-motifs not described anywhere yet.

According to the invention suitable Superstructure-forming nucleic acid sequences have a length from 8 to 100, especially 8 to 40, preferably 14 to 40, preferred 20 to 40 and most preferably from 30 to 40 nucleotides on.

The can be used according to the invention Superstructure-forming nucleic acid sequences can be eukaryotic or prokaryotic origin (also hydrolyzed or partially hydrolyzed) be. According to the invention preferred is however synthetic DNA.

• a) Veränderung der Internukleosidbrücken: Austausch von Phosphodiestern gegen Methylphosphonate, Phosphoramidate, Phosphorothioate oder Hydroxylamine;
• b) Veränderung der Zuckerkomponenten: Austausch der Ribose gegen diverse Hexo- bzw. Pentopyranosen oder 3'-5'-carbocyclisch verbrückte Derivate der 2'-Deoxyribose (Steffens R & Leumann CJ: Tricyclo-DNA: A phosphodiesterbackbone based DNA analog exhibiting strong complementary base-pairing properties. J Am Chem Soc; 119: 11548–11549, 1997);
• c) Austausch des Strangrückgrats: Austausch der Polyesterketten auf Basis von Zucker-Phosphat-Einheiten gegen Carboxamidketten auf Basis von Aminosäurederivaten wie N-(2-Aminoethyl)-glycin-Einheiten;

The superstructure-forming nucleic acid sequences which can be used according to the invention can be chemically modified completely (all nucleotides) or partially (only a few nucleotides) in a manner known to the person skilled in the art. Preferred modifications are, for example:

• a) Alteration of the internucleoside bridges: Exchange of phosphodiesters for methylphosphonates, phosphoramidates, phosphorothioates 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'-deoxyribose (Steffens R & Leumann CJ: Tricyclo-DNA: A phosphodiester-based DNA analog exhibiting strong complementary base-pairing properties, J Chem Chem, 119: 11548-11549, 1997);
• 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 according to the invention preferred are phosphorothioates (PTO).

in the The scope of the present invention is used under epithelial cover tissue on the one hand covering the outer body surface Skin (consisting of subcutis, corium and epidermis) understood, on the other hand the tissue lining the hollow organs and body cavities, including the Epithelia of the uterus and the mouth.

"Inflammatory changes" means in the context of present invention "of an acute or chronic inflammation affected. "The inflammation can by biological (eg pathogens, autoimmune reactions, TNF), chemical (eg poisons, irritants) or physical (eg. B. UV radiation, osmoti cal changes, mechanical stress, heat stress) Noxa or stressors conditional be.

A acute inflammation is due to sudden onset marked with rapid, often violent course over hours or days.

The Cardinal symptoms of acute inflammation are rubor (redness by Vasodilation), tumor (tissue swelling due to inflammatory Exudate), Calor (warming due to increased tissue perfusion), Dolor (pain through Nerve irritation) as well as functio leasa (disturbed function).

• a) Zelluläre Mediatoren: biogene vasoaktive Amine (Histamin und Serotonin), Arachidonsäurederivate (Leukotriene, Prostaglandine, Prostazyklin, Thromboxan A2), plättchenaktivierender Faktor (PAF), Zytokine (Interleukine, TNF-a, Interferone), NO.
• b) Plasmamediatoren: Komplementsystem, Gerinnungs- und fibrinolytisches System, Kallikrein-Kinin-System

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-a, interferons), NO.
• b) Plasma mediators: complement system, coagulation and fibrinolytic system, kallikrein-kinin system

The The most well-known forms of the acute inflammation are the exudative inflammation, serous inflammation, fibrinous inflammation, purulent Inflammation, haemorrhagic Inflammation, necrotizing and ulcerating inflammation, gangrenous inflammation as well the acute lymphocytic Inflammation.

Typical for one chronic inflammation is, however, a long course (weeks, months or years) with often creeping onset and developing symptoms, in particular a persistence of injury.

A by means of a preparation according to the invention preferably inflammatory disease to be treated is the periodontal disease. Periodontal disease is an infectious disease that in most cases caused 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 payout of harmful Substances, especially lipopolysaccharides, activated by the bacteria the immune system of the host and triggers the discharge of inflammatory mediators and MMPs (matrix metallo-proteases) the monocytes out. Proinflammatory cytokines such as IL-1β and TNF-a in turn activate the fibroblasts of the surrounding tissue, the in turn, the distribution amplify from MMPs. Activated macrophages and fibroblasts also reduce expression from TIMPs. The result is an increase in the net activity of MMPs and the destruction of the surrounding tissue.

in the Initial stage of periodontal disease arises through the MMP-mediated resolution small amounts of connective epithelial tissue between gums and the tooth root surface one Pocket that gives the bacteria access to the deeper layers provides and thus allows the progression of the disease. The Reduction of destruction the extracellular Matrix is therefore a promising approach to treatment and Prophylaxis of periodontal disease.

The the epithelial covering tissue with the aid of the preparation according to the invention provide supplied nucleic acids in the epithelial covering tissue for a suppression of the excess immune response and thereby for a regulated balance between collagen buildup and degradation.

The inventive preparation is also for the prophylaxis and treatment of various other diseases or unwanted conditions suitable, in particular flammable conditioned aging, psoriasis, atopic eczema, "dry Skin ", alopecia arreata, vitiligo, bullous Diseases, rejection reactions (graft-versus-host reactions), UV-related skin inflammation as well as malfunctions the epidermal barrier enumerated on p. 2 of WO 98/32444 which is hereby incorporated by reference.

in the Contrary to steroid therapy is when using the preparation of the invention not with unwanted Effects expected since CpG course represent occurring DNA motifs.

The can be used according to the invention Superstructure-forming nucleic acid sequences can be found in the person skilled in the known manner chemically synthesized or from biological Sources, especially from bacteria, are obtained.

The Effectiveness of nucleic acids in formulations for use especially on the skin depends on the availability of nucleic acids in from 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. Liposomes packed nucleic acids can however, penetrate the stratum corneum of skin models. According to the invention preferred Preparations are therefore those which can be used according to the invention Superstructure-forming nucleic acid sequences contained in liposomes. Equally preferred are preparations, the other suitable carrier systems, eg. B. Nanotechnology-based Systems or penetration enhancers (eg urea, Azone or DMSO).

Especially Preferably, the preparation of suitable liposomes as in the DE-A-197 40 092, to which reference is hereby made in its entirety becomes.

One Another object of the present invention is the use of superstructure-forming nucleic acid sequences for prophylaxis and / or Treatment of epithelial covering tissue, in particular for prophylaxis and / or treatment inflammatory changed epithelial covering tissue.

One Another object of the present invention is a method for the preparation of a cosmetic or pharmaceutical preparation, in particular for prophylaxis and / or treatment changed inflammatory Epithelial covering tissue, characterized in that superstructure-forming Nucleic acid sequences, as for the preparations according to the invention described, with cosmetically and pharmacologically suitable and compatible carriers mixed.

Further objects of the present invention are fabric Softener, Handwaschmittel, Body- and hair care products, hair dye or hand dishwashing detergent, the superstructure-forming nucleic acid sequences, as for the preparations according to the invention described include.

The Superstructure-forming nucleic acid sequences are in the context of the present invention preferably as a component in a cosmetic or pharmaceutical preparation or in laundry softener, hand detergent, Hand dishwashing detergents or personal care products introduced or incorporated.

ever according to the type of formulation the pharmaceutical according to the invention Preparations at least one other auxiliary or additive, such as z. Oils, Protective colloids, plasticizers, antioxidants and / or emulsifiers contain.

in the Case of a dispersion, in particular 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, soy or peanut oil, esters medium-chain vegetable fatty acids or fish oils such as Mackerel, sprat or salmon oil to use.

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

The Dosage and duration of use of the inventively employable superstructure-forming Nucleic acid sequences can be suitably adapted and varied by the person skilled in the art.

The fabric softener according to the invention, hand detergent and hand dishwashing detergents as well as the cosmetic preparations, body and hair care products and hair dyes, 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 can - depending on Type of formulation - as auxiliaries and additives mild surfactants, oils, emulsifiers, superfatting agents, Pearlescent waxes, bodying agents, thickeners, polymers, silicone compounds, Fats, waxes, stabilizers, biogenic agents, deodorants, Antiperspirants, antidandruff agents, film formers, swelling agents, UV sun protection factors, Antioxidants, hydrotropes, preservatives, insect repellents, Self, Solubilizers, perfume oils, dyes and the like.

typical examples for 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, taurides, Fatty acid glutamates, α-olefinsulfonates, Ether carboxylic acids, alkyl oligoglucosides, fatty acid glucamides, Alkylamidobetaines and / or protein fatty acid condensates, the latter preferably based on wheat proteins.

Examples of oil bodies are Guerbet alcohols based on fatty alcohols having 6 to 18, preferably 8 to 10 carbon atoms, esters of linear C ₆ -C ₂₂ fatty acids with linear C ₆ -C ₂₂ fatty alcohols, esters of branched C ₆ -C ₁₃ carboxylic acids ren with 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, erucyl myristate, erucyl , 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 (such as propylene glycol, dimerdiol or trimer triol) and / or Guerbet alcohols, triglycerides based on C ₆ -C ₁₀ fatty acids, liquid mono- / di- / Triglyceridmisungen based on C ₆ -C ₁₈ 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 ₁₂ 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 lin earen and / or branched C ₆ -C ₂₂ alcohols (such as Finsolv ^® TN) linear, or branched, symmetrical or asymmetrical dialkyl ethers having 6 to 22 carbon atoms per alkyl group, ring opening products of epoxidized Fettsäureestern with polyols, silicone oils and / or aliphatic or naphthenic Hydrocarbons, such as. As squalane, squalene or dialkylcyclohexanes.

• (1) Anlagerungsprodukte von 2 bis 30 Mol Ethylenoxid und/oder 0 bis 5 Mol Propylenoxid an lineare Fettalkohole mit 8 bis 22 C-Atomen, an Fettsäuren mit 12 bis 22 C-Atomen, an Alkylphenole mit 8 bis 15 C-Atomen in der Alkylgruppe sowie Alkylamine mit 8 bis 22 Kohlenstoffatomen im Alkylrest;
• (2) C_12/18-Fettsäuremono- und -diester von Anlagerungsprodukten von 1 bis 30 Mol Ethylenoxid an Glycerin;
• (3) Glycerinmono- und -diester und Sorbitanmono- und -diester von gesättigten und ungesättigten Fettsäuren mit 6 bis 22 Kohlenstoffatomen und deren Ethylenoxidanlagerungsprodukte;
• (4) Alkyl- und/oder Alkenylmono- und -oligoglycoside mit 8 bis 22 Kohlenstoffatomen im Alk(en)ylrest und deren ethoxylierte Analoga;
• (5) Anlagerungsprodukte von 15 bis 60 Mol Ethylenoxid an Ricinusöl und/oder gehärtetes Ricinusöl;
• (6) Polyol- und insbesondere Polyglycerinester;
• (7) Anlagerungsprodukte von 2 bis 15 Mol Ethylenoxid an Ricinusöl und/oder gehärtetes Ricinusöl;
• (8) Partialester auf Basis linearer, verzweigter, ungesättigter bzw. gesättigter C_6/22-Fettsäuren, Ricinolsäure sowie 12-Hydroxystearinsäure und Glycerin, Polyglycerin, Pentaerythrit, Dipentaerythrit, Zuckeralkohole (z.B. Sorbit), Alkylglucoside (z.B. Methylglucosid, Butylglucosid, Laurylglucosid) sowie Polyglucoside (z.B. Cellulose);
• (9) Mono-, Di- und Trialkylphosphate sowie Mono-, Di- und/oder Tri-PEG-alkylphosphate und deren Salze;
• (10) Wollwachsalkohole;
• (11) Polysiloxan-Polyalkyl-Polyether-Copolymere bzw. entsprechende Derivate;
• (12) Mischester aus Pentaerythrit, Fettsäuren, Citronensäure und Fettalkohol gemäß DE 1165574 PS und/oder Mischester von Fettsäuren mit 6 bis 22 Koh lenstoffatomen, Methylglucose und Polyolen, vorzugsweise Glycerin oder Polyglycerin,
• (13) Polyalkylenglycole sowie
• (14) Glycerincarbonat.

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) C _12/18 fatty acid _mono- and diesters of addition products of 1 to 30 moles of ethylene oxide with 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 Fatty alcohols, fatty acids, Alkylphenols, glycerol mono- and diesters and sorbitan mono- and diesters of fatty acids or castor oil make known, commercially available products represents.

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 _12/18 fatty acid _mono- and diesters of addition products of ethylene oxide with glycerol are made DE 2024051 PS known as a refatting agent 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. Regarding the glycoside residue, it holds true that both monoglycosides in which a cyclic sugar residue is glycosidically linked to the fatty alcohol is attached, 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 Care ^® 450), Polyglyceryl-3 Beeswax (Cera Bellina ^®), poly glyceryl-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 Kokosalkyldimethylammoniumglycinat, N-acylaminopropyl-N, N-dimethylammoniumglycinate, for example Kokosacylaminopropyldimethylammoniumglycinat, and 2-alkyl-3-carboxylmethyl-3-hydroxyethylimidazoline each having 8 to 18 carbon atoms in the alkyl or acyl group and the 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 understood as meaning those surface-active compounds which, apart from a C _8/18 -alkyl or -acyl group in the molecule, contain at least one free amino group and at least one -COOH or -SO ₃ H group and are capable of forming internal salts. Examples of suitable ampholytic surfactants are N-alkylglycines, N-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.

As superfatting agent can Substances such as lanolin and lecithin and polyethoxylated or acylated lanolin and lecithin derivatives, polyol fatty acid esters, Monoglycerides and fatty acid alkanolamides be used, the latter also as foam stabilizers serve.

When Pearlescent waxes are, for example, suitable: alkylene glycol esters, especially ethylene glycol distearate; Fatty acid alkanolamides, especially coconut fatty acid diethanolamide; Partial glycerides, especially stearic acid monoglyceride; Esters of polyfunctional, optionally hydroxysubstituted carboxylic acids with Fatty alcohols with 6 to 22 carbon atoms, especially long-chain Esters of tartaric acid; Fatty substances, such as, for example, fatty alcohols, fatty ketones, fatty aldehydes, Fatty ethers and fatty carbonates totaling at least 24 carbon atoms specifically, lauron and distearyl ether; Fatty acids like stearic acid, hydroxystearic 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.

When Bodying agents are primarily fatty alcohols or hydroxy fatty alcohols with 12 to 22 and preferably 16 to 18 carbon atoms and next to it Partial glycerides, fatty acids or hydroxy fatty acids into consideration. Preference is given to a combination of these substances with alkyl oligoglucosides and / or fatty acid N-methylglucamides same chain length and / or Polyglycerol poly-12-hydroxy stearates.

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 a quaternized hydroxyethyl cellulose obtainable from Amerchol under the name Polymer JR 400 ^®, cationic starch, copolymers of diallyl ammonium salts and acrylamides, quaternized vinylpyrrolidone / vinylimidazole polymers, for example Luviquat ^® (BASF) , Condensation products of polyglycols and amines, quaternized collagen polypeptides, for example lauryldimonium hydroxypropyl hydrolyzed collagen (Lamequat® ^® L / Grunau), quaternized wheat polypeptides, polyethyleneimine, cationic silicone polymers, for example, amodimethicone, copolymers of adipic acid and dimethylaminohydroxypropyl diethylenetriamine (Cartaretine ^® / Sandoz), copolymers of acrylic acid with dimethyldiallylammonium chloride (Merquat ^® 550 / Chemviron) , Polyaminopolyamides, such as described in FR 2252840 A and their crosslinked water-soluble polymers, cationic chitin derivatives such as quaternized chitosan, 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 Celanese, quaternized ammonium salt polymers, for example Mirapol ^® A-15, Mirapol ^® AD-1, Mirapol ^® AZ-1 the company Miranol.

When anionic, zwitterionic, amphoteric and nonionic polymers For example, vinyl acetate / crotonic acid copolymers, vinyl pyrrolidone / 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.Butylaminoethylmethacrylat / 2 Hydroxyproyl methacrylate copolymers, Polyvinylpyrrolidone, vinylpyrrolidone / vinylacetate copolymers, vinylpyrrolidone / dimethylaminoethylmethacrylate / vinylcaprolactam terpolymers and optionally derivatized cellulose ethers and silicones in question.

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

typical examples for Fats are glycerides, as waxes come u.a. natural waxes, e.g. candelilla, Carnauba wax, japan wax, esparto wax, cork wax, guaruma wax, rice germ oil wax, Sugarcane wax, ouricury wax, montan wax, beeswax, shellac wax, Spermaceti, lanolin (wool wax), cudgel fat, Ceresin, ozokerite (groundwax), petrolatum, paraffin waxes, microwaxes; chemically modified waxes (hard waxes), e.g. Montanesterwachse, Sasol waxes, hydrogenated jojoba waxes and synthetic waxes, such as e.g. Polyalkylene waxes and polyethylene glycol waxes in question.

When Stabilizers can Metal salts of fatty acids, such as. Magnesium, aluminum and / or zinc stearate or ricinoleate be used.

Under biogenic agents 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 to understand.

cosmetic Deodorants (deodorants) counteract body odors, cover up or eliminate them. Body odors arise by the action of dermal bacteria on apocrine sweat, taking unpleasant-smelling degradation products are formed. Accordingly contain deodorants active substances that act as germ-inhibiting agents, Enzyme inhibitors, odor absorbers or odor maskers act.

When antimicrobial agents, optionally the cosmetics of the invention to be added are basically all substances active against gram-positive bacteria are suitable, such as z. For example, 4-hydroxybenzoic acid and their 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-chloro phenol), 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. B. 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 such as trimethyl citrate, tripropyl, triisopropyl, tributyl citrate and especially 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.

When Odor absorbers are suitable substances, the odor-forming compounds record and largely hold. They lower the partial pressure of the individual components and thus also reduce their propagation speed. It is important that perfumes must remain undisturbed. odor absorbers have no activity against bacteria. They contain, for example as main ingredient a complex zinc salt of ricinoleic acid or special, largely odorless fragrances that the expert known as "fixators", like z. B. Extracts of Labdanum or Styrax or certain Abietinsäurederivate. As an odor masker Fragrances or perfume oils that work additionally to their function as odor maskers Give the deodorants their respective scent. As perfume oils are For example, called mixtures of natural and synthetic fragrances. natural Fragrances are extracts of flowers, Stems and leaves, fruits, Fruit peels, roots, woods, herbs and grasses, Needles and twigs as well as resins and balsams. Furthermore come animal Raw materials in question, such as civet and castoreum. typical synthetic fragrance compounds are products of the ester type, Ethers, aldehydes, ketones, alcohols and hydrocarbons. fragrance compounds the type of esters are e.g. Benzyl acetate, p-tert-butylcyclohexyl acetate, Linalyl acetate, phenylethyl acetate, linalyl benzoate, benzyl formate, Allyl cyclohexyl propionate, styrallyl propionate and benzyl salicylate. Count to the Ethern for example, benzyl ethyl ether, to the aldehydes e.g. the linear ones Alkanals of 8 to 18 carbon atoms, citral, citronellal, citronellyloxyacetaldehyde, Cyclamenaldehyde, Hydroxycitronellal, Lilial and Bourgeonal, to the Ketones e.g. the Jonone and Methylcedrylketone, to the alcohols Anethole, citronellol, eugenol, isoeugenol, geraniol, linalool, phenylethyl alcohol and terpineol, the hydrocarbons mainly include the terpenes and balsams. However, preference is given to using mixtures of different fragrances, which together create an appealing scent. Also essential oils lesser Volatility, The most commonly used as Aro makomponenten are suitable as perfume oils, e.g. Sage oil, Chamomile oil, Clove oil, 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 be bergamot oil, Dihydromyrcenol, Lilial, Lyral, Citronellol, Phenylethylalcohol, α-Hexylcinnamaldehyde, Geraniol, benzylacetone, cyclamenaldehyde, linalool, Boisambrene Forte, Ambroxan, indole, hedione, sandelice, lemon oil, tangerine oil, orange oil, allylamyl glycolate, Cyclovertal, lavandin oil, Muscat sage oil, β-damascone, geranium 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, used.

• (a) adstringierende Wirkstoffe,
• (b) Ölkomponenten,
• (c) nichtionische Emulgatoren,
• (d) Coemulgatoren,
• (e) Konsistenzgeber,
• (f) Hilfsstoffe wie z. B. Verdicker oder Komplexierungsmittel und/oder
• (g) nichtwässrige Lösungsmittel wie z. B. Ethanol, Propylenglykol und/oder Glycerin.

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.

When Astringent antiperspirant active ingredients are especially suitable Salts of aluminum, zirconium or zinc. Such suitable antiperspirant active agents are e.g. Aluminum chloride, Aluminum chlorohydrate, aluminum dichlorohydrate, aluminum sesquichlorohydrate and their complexes z. With propylene glycol-1,2. Aluminiumhydroxyallantoinat, Aluminum chloride tartrate, aluminum zirconium trichlorohydrate, aluminum zirconium tetrachlorohydrate, Aluminum zirconium pentachlorohydrate and their complex compounds z. With amino acids like glycine.

• • entzündungshemmende, hautschützende oder wohlriechende ätherische Öle,
• • synthetische hautschützende Wirkstoffe und/oder
• • öllösliche Parfümöle.

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

• • 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 Thickening agents, e.g. water-soluble natural or synthetic polymers such as e.g. Xanthan gum, hydroxyethyl cellulose, Polyvinylpyrrolidone or high molecular weight polyethylene oxides.

When Anti-dandruff agents can Climbazole, Octopirox and Zinkpyrithion be used.

common Film formers are, for example, chitosan, microcrystalline chitosan, quaternized chitosan, polyvinylpyrrolidone, vinylpyrrolidone-vinyl acetate copolymers, polymers the acrylic acid series, quaternary Cellulose derivatives, collagen, hyaluronic acid or salts thereof and the like Links.

When Swelling agent for aqueous phases can montmorillonites, Clay minerals, pemulen and alkyl-modified carbopol types (Goodrich) serve. Other suitable polymers or swelling agents can the overview by R. Lochhead in Cosm.Toil. 108, 95 (1993).

• • 3-Benzylidencampher bzw. 3-Benzylidennorcampher und dessen Derivate, z.B. 3-(4-Methylbenzyliden)campher wie in der EP 0693471 B1 beschrieben;
• • 4-Aminobenzoesäurederivate, vorzugsweise 4-Dimethylamino)benzoesäure-2-ethylhexylester, 4-(Dimethylamino)benzoesäure-2-octylester und 4-(Dimethylamino)benzoesäureamylester;
• • Ester der Zimtsäure, vorzugsweise 4-Methoxyzimtsäure-2-ethylhexylester, 4-Methoxyzimtsäurepropylester, 4-Methoxyzimtsäureisoamylester 2-Cyano-3,3-phenylzimtsäure-2-ethylhexylester (Octocrylene);
• • Ester der Salicylsäure, vorzugsweise Salicylsäure-2-ethylhexylester, Salicylsäure-4-isopropylbenzylester, Salicylsäurehomomenthylester;
• • Derivate des Benzophenons, vorzugsweise 2-Hydroxy-4-methoxybenzophenon, 2-Hydroxy-4-methoxy-4'-methylbenzophenon, 2,2'-Dihydroxy-4-methoxybenzophenon;
• • Ester der Benzalmalonsäure, vorzugsweise 4-Methoxybenzmalonsäuredi-2-ethylhexylester;
• • Triazindenivate, wie z.B. 2,4,6-Trianilino-(p-canbo-2'-ethyl-1'-hexyloxy)-1,3,5-triazin und Octyl Triazon, wie in der EP 0818450 A1 beschrieben oder Dioctyl Butamido Triazone (Uvasorb^® HEB);
• • Propan-1,3-dione, wie z.B. 1-(4-tert.Butylphenyl)-3-4'methoxyphenyl)propan-1,3-dion;
• • Ketotricyclo(5.2.1.0)decan-Derivate, wie in der EP 0694521 B1 beschrieben.

By UV sun protection factors, for example, liquid or crystalline organic substances (light protection filters) are to be understood, which are able to absorb ultraviolet rays and release the absorbed energy in the form of longer-wave radiation, for example heat, at room temperature. UVB filters can be oil-soluble or water-soluble. Examples of oil-soluble substances are:

• • 3-Benzylidencampher or 3-Benzylidennorcampher and its derivatives, eg 3- (4-methylbenzylidene) camphor as in EP 0693471 B1 described;
• 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, such as 2,4,6-trianilino (p-canbo-2'-ethyl-1'-hexyloxy) -1,3,5-triazine and octyl triazone, as described in U.S. Pat EP 0818450 A1 Dioctyl Butamido Triazone or described (Uvasorb HEB ^®);
• Propane-1,3-diones such as 1- (4-tert-butylphenyl) -3-4'-methoxyphenyl) propane-1,3-dione;
• • Ketotricyclo (5.2.1.0) decane derivatives as described in U.S. Pat EP 0694521 B1 described.

• • 2-Phenylbenzimidazol-5-sulfonsäure und deren Alkali-, Erdalkali-, Ammonium-, Alkylammonium-, Alkanolammonium- und Glucammoniumsalze;
• • Sulfonsäurederivate von Benzophenonen, vorzugsweise 2-Hydroxy-4-methoxybenzophenon-5-sulfonsäure und ihre Salze;
• • Sulfonsäurederivate des 3-Benzylidencamphers, wie z.B. 4-(2-Oxo-3-bornylidenmethyl)benzolsulfonsäure und 2-Methyl-5-(2-oxo-3-bornyliden)-sulfonsäure und deren Salze.

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, such as 4- (2-oxo-3-bomylidenemethyl) benzenesulfonic acid and 2-methyl-5- (2-oxo-3-bomylidene) -sulfonic acid and salts thereof.

As a typical UV-A filter in particular derivatives of benzoylmethane are suitable, 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 enamine compounds as described in U.S.P. 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, for example Titandioxid 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-carnosine, D-carnosine, L-carnosine and their derivatives (eg anserine) , Chlorogenic acid and their 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) and also Sulfoximinverbindungen (eg Buthioninsulfoximine, Homocysteinsulfoximin, Butioninsulfone, penta-, hexa-, Heptathioninsulfoximin) in very low tolerated dosages (eg pmol to mol / kg), further (metal) chelators (eg α-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 de derivatives (for example γ-linolenic acid, linoleic acid, oleic acid), folic acid and derivatives thereof, ubiquinone and ubiquinol and their derivatives, vitamin C and derivatives (eg ascorbyl palmitate, magnesium ascorbyl phosphate, ascorbyl acetate), tocopherols and derivatives (eg vitamin E acetate) , Vitamin A and derivatives (vitamin A palmitate) and benzylic resin, benzylic acid, rutinic acid and their derivatives, α-glycosylrutin, ferulic acid, furfurylidene glucitol, carnosine, butylhydroxytoluene, butylhydroxyanisole, nordihydroguaiacetic acid, nordihydroguiaretic acid, trihydroxybutyrophenone, uric acid and its derivatives, mannose and their derivatives Derivatives, superoxide dismutase, zinc and its derivatives (eg ZnO, ZnSO ₄ ) selenium and its derivatives (eg selenium methionine), stilbenes and their derivatives (eg stilbene oxide, trans-stilbene oxide) and the inventively suitable Deri derivatives (salts, esters , Ethers, sugars, nucleotides, nucleosides, peptides and lipids) of these drugs.

In addition, according to the invention compounds for suppression or reduction of skin disorders added, which are induced by UV radiation, in particular Activators of peroxisome proliferator-activated receptors (PPAR activators), as described in WO 02/38150, hereby fully incorporated herein by reference Reference is made.

• • Glycerin;
• • Alkylenglycole, wie beispielsweise Ethylenglycol, Diethylenglycol, Propylenglycol, Butylenglycol, Hexylenglycol sowie Polyethylenglycole mit einem durchschnittlichen Molekulargewicht von 100 bis 1.000 Dalton;
• • technische Oligoglyceringemische mit einem Eigenkondensationsgrad von 1,5 bis 10 wie etwa technische Diglyceringemische mit einem Diglyceringehalt von 40 bis 50 Gew.-%;
• • Methyolverbindungen, wie insbesondere Trimethylolethan, Trimethylolpropan, Trimethylolbutan, Pentaerythrit und Dipentaerythrit;
• • Niedrigalkylglucoside, insbesondere solche mit 1 bis 8 Kohlenstoffen im Alkylrest, wie beispielsweise Methyl- und Butylglucosid;
• • Zuckeralkohole mit 5 bis 12 Kohlenstoffatomen, wie beispielsweise Sorbit oder Mannit,
• • Zucker mit 5 bis 12 Kohlenstoffatomen, wie beispielsweise Glucose oder Saccharose;
• • Aminozucker, wie beispielsweise Glucamin;
• • Dialkoholamine, wie Diethanolamin oder 2-Amino-1,3-propandiol.

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;
• Dialcohols, such as diethanolamine or 2-amino-1,3-propanediol.

When Preservatives are, for example, phenoxyethanol, Formaldehyde solution, parabens, Pentanediol or sorbic acid and the other listed in Appendix 6, Part A and B of the Cosmetics Regulation Classes. Insect repellents are N, N-diethyl-m-toluamide, 1,2-pentanediol or ethyl butylacetylaminopropionate in question, is 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, for example, benzyl acetate, phenoxyethyl isobutyrate, p-tert-butylcyclohexyl acetate, linalyl acetate, dimethylbenzylcarbinyl acetate, phenylethyl acetate, linalyl benzoate, benzylformate, ethylmethylphenylglycinate, allylcyclohexylpropionate, styrallylpropionate and benzylsalicylate. 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 ionones, Α-Isomethylionon and Methylcedrylketon, to the alcohols anethole, citronellol, eugenol, isoeugenol, geraniol, linalool, phenylethyl alcohol and terpineol, the hydrocarbons include mainly the terpenes and balsams. Preferably, however, mixtures of different fragrances are used, which together produce an attractive fragrance. Also essential oils of lower volatility, which are mostly used as flavoring components, are suitable as perfume oils, eg sage oil, chamomile oil, clove oil, lemon balm oil, mint oil, cinnamon 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, 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, romilllat, irotyl and floramate alone or in mixtures.

When Dyes can the for used for cosmetic purposes suitable and approved substances as described, for example, in the publication "Cosmetic Colorants" of the Dye Commission the Deutsche Forschungsgemeinschaft, Verlag Chemie, Weinheim, 1984, Pp. 81-106. These dyes are commonly in concentrations of 0.001 to 0.1 wt .-%, based on the total Mixture, used.

To the body care compositions according to the invention counting also dentifrices and general oral care products (Oral care products).

• – Putz- und Polierkörper wie z.B. Kreide, Kieselsäuren, Aluminiumhydroxid, Aluminiumsilikate, Calciumpyrophosphat, Dicalciumphosphat, unlösliches Natriummetaphosphat oder Kunstharzpulver;
• – Feuchthaltemittel wie z.B. Glycerin, 1,2-Propylenglycol, Sorbit, Xylit und Polyethylenglycole
• – Bindemittel und Konsistenzregler, z.B. natürliche und synthetische wasserlösliche Polymere und wasserlösliche Derivate von Naturstoffen, z.B. Celluloseether, Schichtsilikate, feinteilige Kieselsäuren (Aerogel-Kieselsäuren, pyrogene Kieselsäuren)
• – Aromen, z.B. Pfefferminzöl, Krauseminzöl, Eukalyptusöl, Anisöl, Fenchelöl, Kümmelöl, Menthylacetat, Zimtaldehyd, Anethol, Vanillin, Thymol sowie Mischungen dieser und anderer natürlicher und synthetischer Aromen
• – Süßstoffe wie z.B. Saccharin-Natrium, Natrium-cyclamat, Aspartame, Acesulfan K, Steviosid, Monellin, Glycyrrhicin, Dulcin, Lactose, Maltose oder Fructose
• – Konservierungsmittel und antimikrobielle Stoffe wie z.B. p-Hydroxybenzoesäureester, Natriumsorbat, Triclosan, Hexachlorphen, Phenylsalicylsäureeter, Thymol usw.
• – Pigmente wie z.B. Titandioxid oder Pigmentfarbstoffe zur Erzeugung farbiger Streifen
• – Puffersubstanzen z.B. primäre, sekundäre oder tertiäre Alkaliphosphate, Citronen-säure/Na-Citrat
• – wundheilende und entzündungshemmende Wirkstoffe, z.B. Allantoin, Harnstoff, Azulen, Panthenol, Acetylsalicylsäure-Derivate, Pflanzenextrakte, Vitamine, z.B. Retinol oder Tocopherol.

Toothpastes contain z. Typically:

• - Cleaning and polishing such as chalk, silicas, aluminum hydroxide, aluminum silicates, calcium pyrophosphate, dicalcium phosphate, insoluble sodium metaphosphate or synthetic resin powder;
• Humectants such as glycerin, 1,2-propylene glycol, sorbitol, xylitol 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 silicic acids (airgel-silicic acids, pyrogenic 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 such as saccharin sodium, sodium cyclamate, aspartame, acesulfan K, stevioside, monellin, glycyrrhicin, dulcine, lactose, maltose or fructose
• Preservatives and antimicrobials such as p-hydroxybenzoic acid esters, sodium sorbate, triclosan, hexachlorophene, phenylsalicylic acid ethers, thymol, etc.
• - Pigments such as titanium dioxide or pigment dyes to produce colored stripes
• - Buffer substances such as primary, secondary or tertiary alkali metal phosphates, citric acid / Na citrate
• - Wound-healing and anti-inflammatory agents, eg allantoin, urea, azulene, panthenol, acetylsalicylic acid derivatives, plant extracts, vitamins, eg retinol or tocopherol.

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

The The following examples describe the invention, but without it limit:

example 1

The in this example described anti-inflammatory effects refer to in vitro tests on HaCaT cell cultures. When The parameter became their IL-8 basal level in the cell culture supernatant examined by ELISA. The Interleukin IL-8 serves primarily as chemotactic factor for neutrophilic granulocytes, thus promoting inflammation. In addition, IL-8 is a pro-angiogenesis factor - so it promotes the sprouting of new vessels. It will of HaCaT cells increased after stimulation with TNFa or IL-1, however, these cells also have well-measurable basal levels. The anti-inflammatory Effect of non-CpG was also induced by measurements of TNFα IL-8 and IL-6 levels confirmed, However, these data will not be discussed in detail below. It can thus from a prophylactic (suppression of the basal level) and a therapeutic (suppression after induction) effect become.

Non-CpG studies show that not all ODNs are equally anti-inflammatory. Considering homo-PTO with a length of 20 bases each, the following sequence results with respect to the effect with poly-G as the most effective ODN: poly-G>poly-I>poly-C>poly-T> poly-A (s , 1A ). Looking at the corresponding homo-phosphodiester (homo-PDE), only poly-G and poly-C show an anti-inflammatory However, this effect is significantly worse than that of the corresponding PTO (s. 1B ). Poly-I was not tested as PDE.

Example 2:

Investigations with poly-AG- and poly-AC-random-heteropolymers as PTO indicate that it is not the well-defined sequences but the content of guanine or cytosine (or hypoxanthine) that is crucial for the effect of non-CpG ( s. 2A u. B):

What the length As far as the oligonucleotides are concerned, one of them appears. concentration of 4μM, a minimum length from 14 to 16 bases for an efficient anti-inflammatory effect is required. One short poly-C-ODN (8mer, PTO) also showed at higher concentrations one - if also very weak - effect, while for longer poly-C-ODN (30 and 40mers) to achieve an improvement in the effect is.

DNA backbone derivatives (Deoxyribo phosphorothioate derivative, propanediol phosphorothioate derivative; 20mers) no or only a very slight reduction of the IL-8 basal level from HaCaT cells.

example 3: Anti-inflammatory effect of non-CpG in vivo. Complementary to the In vitro findings could also be an anti-inflammatory Confirm the effect of non-CpG.

For this was the influence of a contact allergy by a poly-C-containing (20mer, PTO) ointment shown in mouse model.

Around to trigger an experimental contact allergy will be on day 0 respectively 100μl 0.5% DNFB (dinitrofluorobenzene) in acetone / olive oil (1/4) on the dorsal skin from BALB / c nude mice applied. This causes a sensitization of the test animals to DNFB, which is an obligate contact allergen.

At Day 5, re-exposure occurs: 30μl 0.3% DNFB in acetone / olive oil applied to each side of an ear. Already after 24 hours it comes to an inflammatory reaction at the ear. This expresses itself especially in an ear swelling. Histologically, there is one Spongiosis and immigration of leukocytes. Ear swelling and histological processing are the outcomes to ensure efficacy of To examine test substances.

• 1.) DAC-Basiscreme (Negativkontrolle ohne Wirkstoff)
• 2.) 1,4% poly-C-PTO in DAC
• 3.) Dermatop^® (= Positivkontrolle), Dermatop^® ist eine von der Firma Aventis erhältliche Klasse-2-steroidhaltige Salbe (Prednicarbat).

The following test substances were tested for the prophylaxis of sensitized animals:

• 1.) DAC-base cream (negative control without active ingredient)
• 2.) 1.4% poly-C-PTO in DAC
• 3.) Dermatop ^® (= positive control), Dermatop ^® is a commercially available by the company Aventis class-2-steroid-containing ointment (prednicarbate).

The experimental setup is schematic in the 3 shown.

Results:

• 1.) 4 shows the ear thickness difference between treated ears (test substance in combination with DNFB) and untreated ears. A minimal difference is therefore synonymous with a high effectiveness of the test substance. The graph shows that the differences in ear thickness due to the use of Dermatop ^® and poly-C-PTO are significantly lower compared to active ingredient-free DAC-base cream. The measured values suggest that 1.4% poly-C-PTO in DAC and Dermatop ^® have a similar effect.
• 2.) The results of HE stained tissue sections are in 5 shown. It has been shown that the use of DAC-base cream leads to a strong loosening of the tissue (spongiosis), which also explains the thickness increase of the ears.

In addition, a massive inflammatory infiltrate ( "blue cells") is apparent in the outer layers of the tissue. After use of the steroid-containing ointment Dermatop ^® the inflammatory infiltrate is significantly reduced. A similar reduction is even after treatment with 1.4% poly-C PTO recognizable.

Example 4:

The The results presented give a strong indication that the ODN superstructures described above are anti-inflammatory act on the skin and thus represent a new active motive.

It was experimentally the influence of random heteropolymers with 50% adenine and 50% cytosine or guanine content at the IL-8 basal level examined by HaCaT keratinocytes.

The effect was compared with ODN of the same length and base composition, but in an alternating sequence (CACACACA ... or GAGAGA-GA ...). In an alternate arrangement, the ODNs do not contain consecutive guanines or cytosines and therefore should not be able to form G-quadruplexes, "frayed wires" or i-motifs! 10 can be seen, leads the alternating arrangement of the bases in the case of Po ly-AG hetero-PTO leads to a significantly weaker IL-8 reduction that is no longer significantly different from the control. This is a clear indication of the involvement of G-quadruplexes or "frayed wires" in the effect of non-CpG.

List of pictures:

1 : The bases determine the suppressive effect of 20-nucleotide homopolymers on IL-8 release in skin keratinocytes (HaCaT). In the control (-) the cells were incubated for 18 hours with culture medium without oligonucleotides, in the other batches the ODN was added in a concentration of 4 .mu.M. (A) PTO containing 100% adenine (100A-PTO), thymine (100T-PTO), cytosine (100C-PTO), guanine (100G-PTO) or hypoxanthine (100I-PTO). (B) PDE containing 100% adenine (100A-PDE), thymine (100T-PDE), cytosine (100C-PDE) or guanine (100G-PDE).

2 : The content of guanine and cytosine in a nucleotide sequence determines the suppressive effect on IL-8 release in skin keratinocytes (Ha-CaT). In the control (-), the cells were incubated for 18 hours with culture medium without PTO (20mers), in the other approaches, the PTO added in a concentration of 4μM. (A) Statistical reduction of the guanine content in poly-AG random heteropolymers from 100% to 0% leads to the abolition of the anti-inflammatory effect. 100G-PTO = 100% guanine, 75G25A-PTO = 75% guanine and 25% adenine, 50G50A-PTO = 50% guanine and 50% adenine, 25G75A-PTO = 25% guanine and 75% adenine, 100A-PTO = 100% Adenine, respectively statistical distribution of the bases. (B) Statistical reduction of cytosine content in poly-AC random heteropolymers from 100% to 0% leads to the abolition of the anti-inflammatory effect. 100C-PTO = 100% cytosine, 75C25A-PTO = 75% cytosine and 25% adenine, 50C50A-PTO = 50% cytosine and 50% adenine, 25C75A-PTO = 25% cytosine and 75% adenine, 100A-PTO = 100% Adenine, respectively statistical distribution of the bases.

3 : Schematic experimental set-up for testing substances for prophylaxis in sensitized animals. On day 0, the animals are sensitized with DNFB. The sensitization phase is 5 days. On the 5th day one ear of each animal is treated with the test substances. After 2h DNFB is applied again ('challenge'). On the 6th day the ear thicknesses are measured and the ear tissue examined histologically.

4 : Ear thickness differences after treatment with test substances and DNFB (see diagram above, 3 ). n, number of experimental animals.

5 : Longitudinal sections through mouse ears after treatment with test substances and DNFB (see diagram above, 3 ) in the HE stain.

6 : Formation of a G-Quartet on Hoogsteen Base Pairings (Figure modified according to Shafer RH & Smirnov I: Biological Aspects of DNA / RNA quadruplexes, Biopolymers, 56: 209-227, 2001). Left schematic representation of a guanine quartet, right structure of a guanine quartet from the crystal structure of the linear quadruplex [d (TGGGGT)] ₄ .

7 : Formation of inter- and intea-molecular G-quadruplexes (modified according to Shafer & Smirnov, see above). Schematic representation of G quadruplexes of four (A), two (B) or one (C) strand.

8th : Formation of Frayed Wires of d (T ₁₅ G _n ) oligonucleotides (Figure modified according to Poon K & MacGregor RB Jr: Formation and structural determinants of multi-stranded guanine-rich DNA complexes., Biophys Chem., 84: 205-216 , 2000).

9 : The formation of i-motifs of cytosine-rich nucleotide sequences. (A) CC ⁺ base pairing, formation of three hydrogen bonds after protonation of a cytosine. (B) Schematic representation of an intramolecular i motif. (A) and (B) (modified according to Phan AT & Mergny JL: Human telomeric DNA: G-quadruplex, i-motif and Watson-Crick double helix Nucleic Acid Res, 30 (21): 4618-4625, 2002). (C) Schematic representation of an intermolecular i-motif (modified by Fedoroff OY, Rangan A, Chemeris W, Hurley LH: Cationic porphyrins promote the formation of i-motif DNA and bind peripherally by a nonintercalative mechanism, Biochemistry; 39: 15083-15090 , 2000).

10 : The alternating arrangement of guanines and adenines in poly-AG-PTO leads to the loss of reduction of IL8 basal levels in skin keratinocytes (HaCaT) as opposed to randomization of the bases. In the control (-), the cells were incubated for 18 hours with culture medium without PTO (20mers), in the other approaches, the PTO added in a concentration of 4μM. PTO: 100G PTO = 100% guanine; 50G50A-PTO = 50% guanine and 50% adenine, statistical distribution; 50G50A old PTO = 50% guanine and 50% adenine, alternate arrangement;

Claims (13)

Cosmetic or pharmaceutical preparation for the prophylaxis and / or treatment of epithelial covering tissue, characterized in that it contains superstructure-forming nucleic acid sequences contains. Preparation according to claim 1, characterized in that that the superstructure to be formed is selected from G quadruplexes, Frayed Wires or i-motives. Preparation according to one of claims 1 or 2, characterized in that the superstructure-forming nucleic acid sequences are selected under C, G or I rich sequences containing C, G or I in the range of 25% to 100%, preferably 50% to 100%, more preferably 75% to 100% and most preferably 100 %. Preparation according to one of the preceding claims, characterized in that the superstructure-forming nucleic acid sequences selected are among poly-I homopolymers, poly-C homopolymers or poly-G homopolymers. A preparation according to any one of the preceding claims Prophylaxis and / or treatment of inflammatory altered epithelial cover tissue A preparation according to any one of the preceding claims Prophylaxis and / or treatment of inflammatory changes, the selected are under chronic or acute inflammation, especially under exudative inflammation, serous inflammation, fibrinous inflammation, purulent inflammation, haemorrhagic inflammation, necrotizing and ulcerating inflammation, gangrenous inflammation as well as acute lymphocytic Inflammation. A preparation according to any one of the preceding claims Prophylaxis and / or treatment of inflammatory changes, that are caused by noxa or stressors that are selected under: a) biological noxae or stressors, in particular Pathogens, autoimmune reactions, TNF, b) chemical Noxa or stressors, especially poisons, irritants and c) physical noxae or stressors, in particular UV radiation, osmotic changes, mechanical stress, heat stress. A preparation according to any one of the preceding claims Prophylaxis and / or treatment of inflammatory changes, the selected are under flammable conditioned aging processes, psoriasis, atopic eczema, "dry Skin ", alopecia arreata, vitiligo, bullous Diseases, rejection reactions, UV-induced dermatitis and Periodontal disease. Preparation according to one of the preceding claims, characterized in that the superstructure-forming nucleic acid sequences a length from 8 to 100, especially 8 to 40, preferably 14 to 40, preferred 20 to 40 and most preferably from 30 to 40 nucleotides exhibit. Preparation according to one of the preceding claims, characterized in that the superstructure-forming nucleic acid sequences Completely or partially chemically modified. Preparation according to claim 10, characterized that the chemical modification is selected under a) change the internucleoside bridges, in particular exchange of phosphodiesters for methylphosphonates, Phosphoramidates, phosphorothioates or hydroxylamines; b) change the sugar components, in particular exchange of ribose for various Hexo- or pentopyranoses or 3'-5'-carbocyclic bridged derivatives the 2'-deoxyribose; or c) replacement of the strand backbone, in particular replacement 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 phosphodiesters referred to under a) against Phosphorothioate is particularly preferred. Preparation according to one of the preceding claims, characterized characterized in that they are the superstructure-forming nucleic acid sequences Contains packed in liposomes. Laundry softener, hand detergent, Body- and hair care products, hair dye or hand dishwashing detergent, comprising superstructure-forming nucleic acid sequences as in claims 1 to 12 described.