DE102007044093A1 - Nucleic acid-containing cosmetic and / or pharmaceutical preparations for the induction of antimicrobial peptides in epithelial cover tissues - Google Patents

Abstract

The present invention relates to cosmetic and / or pharmaceutical preparations for the treatment of epithelial cover tissue by induction of antimicrobial peptides in the treated epithelial cover tissue and the use of nucleic acids for the induction of antimicrobial peptides in epithelial cover tissues.

Description

The The present invention relates to cosmetic and / or pharmaceutical Preparations for the treatment of epithelial covering tissue by induction antimicrobial peptides in the treated epithelial cover tissue as well as the use of nucleic acids for induction antimicrobial Peptides in epithelial cover tissues.

microbially caused disorders of the skin organ make up a large part the dermatoses in need of treatment. Also a considerable one Part of the cosmetic skin treatments are directed against the skin colonizing microorganisms, for example the control from blackheads and acne, dandruff or unwanted Body odor.

antimicrobial Peptides are an important component of the innate immune system They are highly conserved, typically 15 to 45 amino acids long and effective against a wide range of microorganisms and Viruses. Resistance developments have not yet been observed what may have been with the suspected Mechanism of action is related. So it is believed that the strongly positively charged peptides with the negatively charged membrane The microorganisms interact and there the formation of pores which then lead to a collapse of the transmembrane electrochemical ion gradient to lead. The antibacterial peptides will vary depending on the molecular Structure divided into several groups. The most important human Peptides are the α-defensins, predominantly of granulocytes (eg HNP1 to HNP4) and the intestinal paneth cells (eg HNP5) and the β-defensins, which are mainly expressed of epithelial cells (e.g., HbD-1 to HbD-4). To are of the cathelicidin family nor the LL-37 (granulocytes, Epithelial cells, u. a.) and from the saposin family the granulysin (T cells, NK cells) as important representatives. Some defensins will be constitutively expressed, others only after induction by environmental factors. These environmental factors include u. a. the presence of microorganisms / viruses or components of these, such as LPS or endotoxin. In addition, cellular mediators can also be used such as TNFα, IL-1β, INFγ, activators of Protein kinase C or calcium the expression of antimicrobial Induce peptides.

The Skin is the interface between an organism and its environment and provides protection from external physical, chemical and biological noxae. The latter, in particular, pose a considerable risk potential Bacteria, fungi and viruses are omnipresent and may interfere with a barrier disorder in the skin Invade organism and cause inflammation, the especially in immunosuppressed persons life threatening could be. For some time we know that also the human skin after contact with pathogens antimicrobial Can synthesize peptides. So are human keratinocytes z. B. capable of β-defensins, LL-37 or even psoriasin to synthesize, usually after induction by external stimuli. A An exception to this is the constitutively expressed HbD-1.

microorganisms and viruses are at the onset or aggravation of many diseases, especially many inflammatory skin diseases, involved. Therapeutic approaches known in the art aim at the reduction of germination. Classic will be in addition to hygienic measures, antibiotics, Fungicides and antivirals used. These substances are because of Resistance development often only for a short period of time effective and can cause serious side effects. The latter include u. a. Allergies and disorders intestinal flora (antibiotic-associated diarrhea, fungal infections). In addition, organtoxic can be used in some antibiotics Effects, such as kidney and hearing damage, are added.

The conventional cosmetic treatment options for seborrheic skin, impure skin, pustules and comedones are generally limited to facial cleansing with partially bacteriostatic detergents to reduce excess Talgs, on the mechanical removal of pustules and comedones, on peels to remove dead skin scales and on the Application of disinfecting solutions for containment the regeneration of inflammatory sebaceous follicles. Disadvantage of these treatments, however, is that they are not common to everyone Skin type can be performed (eg Peels on sensitive skin not recommended) and that one Actual symptom reduction is often not can be reached.

Anti-dandruff agents are mainly based on cytostatic, keratolytic and / or microbicidal agents in shampoos and hair lotions. A disadvantage of the existing means, however, is that the active ingredients must be used in some high concentrations, which can lead to undesirable effects on the scalp and hair. In addition, many anti-dandruff agents do not provide a satisfactory effect Dandruff or even in the case of dandruff prophylaxis.

at unpleasant body odor is deodorants or antiperspirants used. Deodorants are based on prevention or coverage from unpleasant body odor by germ repellents, Odor absorbers, perfume oils or enzyme inhibitors (against sweat-decomposing bacterial enzymes) while the antiperspirants for sweat reduction in the underarm area, z. As by astringent substances used. disadvantage of deodorants and antiperspirants are, especially at high or prolonged use, possible side effects such. B. Redness, tightness of the skin or itching.

A Alternative to the mentioned cosmetic and therapeutic treatment options is therefore desirable.

Surprisingly it was found that the use of nucleic acids or nucleic acid-containing mixtures is suitable, the induction to induce antimicrobial peptides in epithelia, or their Promote or enhance induction.

object The present invention is therefore a cosmetic and / or pharmaceutical Preparation for the treatment of epithelial cover tissue by induction antimicrobial peptides in the treated epithelial cover tissue, which is characterized in that it contains nucleic acids contains.

The contained in the preparation according to the invention Nucleic acids can be natural or be of synthetic origin. You can also hydrolyze, partially hydrolyzed or denatured. Preferably, the Nucleic acids selected from synthetic nucleic acids, Nucleic acids of eukaryotic origin, such as nucleic acids from fry or wheat germ and nucleic acids bacterial Origin, in particular with nucleic acids from Escherichia coli and Clostridium perfringens.

preferred contained in the preparation according to the invention Nucleic acids are selected from DNA and RNA, in particular high molecular weight bacterial DNA, low molecular weight bacterial DNA, high molecular weight eukaryotic DNA, low molecular weight eukaryotic DNA and oligonucleotides.

Usable according to the invention Oligonucleotides have a length of 5 to 100, in particular 5 to 70, preferably 10 to 50, preferably 10 to 40 and more particularly preferably from 12 to 30 nucleotides.

The Nucleobases of the preparation according to the invention contained nucleic acids can be methylated or not be methylated.

• a) Veränderung der Internukleosidbrücken: Austausch von Phosphodiestern gegen Methylphosphonate, Phosphoramidate, Phosphorothioate (PTO) 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 nucleic acids 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 (PTO) or hydroxylamines;
• b) Change in 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 analogous to base-pairing properties. J At Chem Soc; 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 phosphorothioate phosphodiester mixmers.

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

Of the Term "treatment" is according to the invention both prophylactically as well as therapeutically.

The preparation according to the invention is especially for the treatment of microbially caused Erkran epithelial covering tissue.

To the diseases in which bacterial agents are involved, include: gonorrhea, Chlamydia infections, Lymphogranulomatosis inguinalis, syphilis, yolk, pinta, borrelia-related Diseases, Ulcer molle, various pyodermas (eg Impetigo contagiosa, staphylococcal pemphigoid, bulla repens, TSS, folliculitis, Frunkel, carbuncle), pyoderma of the sweat gland (sweat gland abscesses), Streptococcal infections (Eerysipel, scarlet fever, etc.), mycobacteriosis (Skin tuberculosis), anthrax, plague and leprosy.

Next these bacterially triggered diseases in the narrower sense Diseases that become worse due to bacterial infections and also advantageous by the invention Preparation can be treated. This favors the skin barrier diminished by the underlying disease invades and spreading bacteria. A diminished skin barrier can be conditioned by the following: pathological changes in the fluid and electrolyte balance, low temperature, Inflammation of mucous membranes, such as cheilitis, inflammation of the nose and vulvovaginitis, eczema, such as seborrheic dermatitis, allergic eczema, contact dermatitis, xerotic dermatitis, photoallergic and phototoxic dermatitis, phytophotodermatitis, radiation dermatitis, Stasis dermatitis, ulcers and erosions resulting from injuries, Burns, bullous (blistering) diseases or ischaemias of the skin or mucous membrane, ichthyoses (keratinization disorders the skin), epidermolysis bullosae, hypertrophic scars and keloids, Changes in the skin due to intrinsic aging and Photoaging, skin blisters due to mechanical friction, skin atrophy (Dilution) by topical use of corticosteroids. It is particularly important to note that a Pre-damage to the skin, as in acne, psoriasis and atopic Eczema facilitates the colonization with bacteria and so to the clinical Overall picture contributes.

Further infectious diseases caused by non-bacterial microorganisms be caused and the means of the invention Preparation can be treated are: Leishmaniasis, Trichomoniasis and diseases involving fungi and yeasts are. Due to the damage to the skin occur frequently simultaneous colonization with different microorganisms, which contributes to the aggravation of the clinical picture. Ultimately, it's the number of germs and individual factors like a diminished barrier effect of the skin and a weakened Immune system, which necessitate medical treatment.

The Preparation according to the invention is also for treatment suitable for virus-related diseases. Examples of this are: HIV, measles, rubella, marigold, papular pupuric gloves and socks syndrome, exanthema subitum, herpes simplex infections, Varicella zoster virus infections, CMV-related diseases, papillomavirus-related Diseases (Condylomata acuminata) and poxvirus diseases (Mollusca contagiosa).

A Reduction of microbial colonization of the skin may also be present be desirable and cosmetic skin treatment effected with the aid of the preparation according to the invention become. So, microbial activity is an important factor in the development of seborrheic skin, impure skin, pustules (Pimples) and comedones (blackheads) - in the latter, especially by Propionibacterium acnes. Skin problems of this kind occur especially in adolescence and young adults but also appear in old age. microbial Activity, mainly by the fungus Pityrosporum ovale, is also an important cause of dandruff formation. Pityrosporum ovale is a skin fungus that also affects the healthy scalp lives without causing discomfort. But the sebaceous glands Strengthens fat, so the fungus grows more. It decomposes the fat of the tallow into aggressive fatty acids, which irritate the epidermis and lead to their increased exfoliation.

One Another cosmetic application field in which the inventive Preparation can be used is the fight unpleasant body odor. Pure, fresh sweat is odorless. However, if it is decomposed by bacteria, z. T. acidic odors, which are perceived as very unpleasant can. Particularly vulnerable to it is the area under the armpits as well as the genital area.

The preparation of the invention is also advantageously used for the treatment of gastric or intestinal diseases. Namely, antimicrobial peptides also play an important role in the protection of the mucous membranes in the digestive tract. In the intestine, they are mainly synthesized by enterocytes and Paneth cells. Paneth cells secrete α-defensins after appropriate stimuli, enterocytes mainly β-defensive both constitutively and after induction. The antimicrobial peptides play an important role in the health of the intestine. So is a Shigella diarrhea z. B. associated with a decreased HbD-1 and LL37 secretion. In addition to bacterial bowel disease, defensins also have an impact the pathophysiology of inflammatory bowel disease. Crohn's disease, for example, has diminished levels of defensin, possibly leading to a weakening of the intestinal barrier function and thus having a lasting effect on the disease. Accordingly, antibiotics also appear to be effective in Crohn's disease.

Of further, the invention can be Preparation also for the treatment of respiratory diseases, as well as the mucous membranes of the airways antimicrobial peptides secrete, in this case, in the overlying biofilm. The electrolyte concentration and composition of this biofilm is regulated by pumps and channels of the pulmonary epithelium and is important for the activity of defensins. you assumes that this homeostasis is due to a genetic Defect in cystic fibrosis transmembrane regulatory protein in cystic fibrosis (cystic fibrosis) is disturbed, resulting in less Activity of the antimicrobial peptides of the lung epithelium leads. This then allows an overpowering bacterial growth, eventually leading to chronic Inflammation leads.

The Preparation according to the invention can be advantageous administered by topical, intralesional or systemic administration become.

The The preparation according to the invention can be used as a single Preparation or in combination with cosmetic or pharmaceutical Active ingredients are applied, for. B. in combination with the so-called. "Chemical peeling" for removing dead skin cells. In this scrub will be mostly AHA (alpha hydroxy acids), PHAs (polyhydroxy acids), TCA (trichloroacetic acid) and glycolic acid used.

Preferably, the nucleic acids contained in the preparation according to the invention are present as oligodeoxynucleotides (ODN). These ODNs preferably have one, two or more CpG motifs, as described, for example, in US Pat DE-A-102 33 994.5 of the applicant, to which reference is hereby made in its entirety.

CpG motifs are distinguished by three major classes of CpG ODN: 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 phosphodiester. Unmodified phosphodiester oligonucleotides are rapidly degraded in vivo by endogenous nucleases. By chemical modification of the phosphodiester backbone, called the phosphorothioate modification is achieved an increased stability of the ODN (O ligo- D esoxy ukleotid n) to 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.

CpG-B ODN have a phosphorothioate backbone and are common several CpG motives. At the 5 'end is often a TCGTCG motif.

CpG ODN C represent a mixture of CpG-A and CpG-B-ODN like the CpG-B ODN have a phosphorothioate backbone frequently several CpG motifs and often at the 5'-end TCGTCG motif. Like the CpG-A ODN, they contain a central CpG motif, which is embedded in a palindromic sequence. They are missing but the guanine consequences.

Further inventively preferred nucleic acids are superstructure-forming ODN, as described for example in the DE-A-103 61 502.4 of the applicant, to which reference is hereby made in its entirety.

Under Superstructure-forming nucleic acid sequences are nucleic acids to understand that are capable of non-covalent bonding to other nucleic acid superstructures, especially G-quadruplexes, to train so-called "Frayed Wires" or "i-motives". Preferably, 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%, more preferably 75% to 100% and most preferably 100%. In a very special way preferred are poly-I-homopolymers, poly-C-homopolymers or poly-G-homopolymers. Where C is cytosine, G is guanine and I for inosine.

Especially effective are C-, G-, T- 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 on the Base composition of 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 also inosine-rich ODNs can via Hoogsteen base pairings Forming G-Quartets that are "stacked" to form of G-quadruplexes. These constitute a multimer of four DNA single strands. The formation can be inter- and intramolecular The quadruplexes are thus one, two or four molecules include. Important here is that the ODN has several consecutive Guanine included. G-quadruplexes can be synthesized by both phosphodiester as well as phosphorothioates.

Next G-quadruplexes, some G-rich oligos can also be called "Frayed Wires. "For this purpose, inter alia, longer G-episodes in ODN necessary. These structures are about them G sequences for the aggregation of ODN, at the very many single strands can be involved.

C-rich Oligonucleotides can be neutral and especially light acidic pH range relatively stable so-called "i-motifs" form. Prerequisite are several episodes of at least two consecutive cytosines. about the protonation of a cytosine can then be three hydrogen bonds be formed into another non-protonated cytosine. I motifs can be used by both phosphodiester and phosphorothioates be formed.

advantageously, is the inventive preparation the Use of antibiotics, fungicides and antivirals reduced or even avoided. This is true for both infectious Diseases as well as for diseases caused by microbial or viral activity worsened. Especially too mention the mode of action of the DNA oligonucleotides. There they induce the production of endogenous antimicrobial peptides and thus stimulate the innate immune system, are side effects, as they are z. B. when using antibiotics occur, less likely. In addition, since so far no resistance developments against these peptides have been observed, it is to be assumed that they are longer Periods can be used without loss of effect.

in the Cosmetic context can be improved by the use of the invention Preparation of the use of microbicidal agents in the above cosmetic application fields are reduced or even avoided. Particularly noteworthy here is the mode of action of the DNA oligonucleotides. Because it is the production of endogenous antimicrobial peptides induce and thus stimulate the innate immune system Side effects, such as B. in the use of alcoholic disinfectant Solutions are less likely. Because these peptides also very effective against a large number of microorganisms are, is a significantly increased efficiency compared to previous ones to expect cosmetic products.

In the present invention it has been shown that, surprisingly, certain DNA oligonucleotides cause the induction of antimicrobial peptides. In particular, it was shown that after topical application of CpG-1-PTO (5'-TCC ATG ACG TTC CTG ACG TT-3), CpG-9 PTO (= deletion mutant of CpG-1 PTO) (5'-GA CG TT-3 ') and 20G-PTO (5'-GGG GGG GGG GGG GGG GGG GG-3') expression of psoriasin in the epidermis of full-skin models is induced (see Example 1). Topical application of 20C-PTO 5'-CCC CCC CCC CCC CCC CCC CC-3 'had no inducing effect. HbD-3 could be detected in the epidermis after topical application of CpG-9-PTO, 20C-PTO and 20G-PTO (see Example 2). To test whether other routes of application lead to the induction of psoriasin and HbD-3, the oligonucleotides were added directly to the culture medium. The oligonucleotides thus first reached the dermis equivalent, from where they were able to diffuse into higher layers of the skin model. In Examples 3 and 4 it is shown that all four oligonucleotides tested lead to the induction of psoriasin and HbD-3. These experiments confirm that an intralesional, systemic application of DNA oligonucleotides is also suitable for inducing antimicrobial peptides in the skin. Furthermore, these Ver prove that the DNA oligonucleotides are chemically stable, and thus that sufficiently high levels of active ingredient can be achieved on this route application. In final experiments on 2D cultures of human keratinocytes, real-time PCR demonstrated that the content of transcripts for HbD-2 was highly regulated after treatment with 20C-PTO and especially with 20G-PTO (see Example 5). These experiments demonstrate that DNA oligonucleotides are capable of inducing antimicrobial peptides in the skin. This results in numerous applications for clinical and cosmetic indi, as described above cations.

The Effectiveness of Nucleic Acids in Formulations for Use especially 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 can be z. B. by Liposomes are improved. According to the invention preferred Preparations are therefore those which can be used according to the invention Nucleic acids are packaged in liposomes. equally preferred are preparations which are other suitable carrier systems, z. As nanotechnology-based systems or Penetrationsenhancer (for example Urea, Azone or DMSO).

Particular preference is given to the preparation of suitable liposomes as in DE-A-197 40 092 to which reference is hereby incorporated by reference.

One Another object of the present invention is the use of nucleic acids for the induction of antimicrobial peptides in epithelial covering tissues.

One Another object of the present invention is a method for the preparation of a cosmetic and / or pharmaceutical preparation for treating epithelial cover tissue by induction antimicrobial Peptides in the treated epithelial cover tissue, characterized that one nucleic acids, as for the inventive Preparations described with pharmacological and / or cosmetic mixed with suitable and compatible carriers.

The Nucleic acids which can be used according to the invention are in the context of the present invention preferably as a component incorporated into a cosmetic and / or pharmaceutical preparation.

In a preferred embodiment contains the Composition according to the invention which can be used according to the invention Nucleic acids and additionally at least one antimicrobial or antiviral substance, in particular an antimicrobial Substance selected from p-hydroxybenzoic acid ester, Triclosan, Hexachlorphen, Phenylsalicylsäureeter, formic acid, Benzoic acid and its salts, benzyl alcohol, benzalkonium chloride, Bromochlorophene, bronopol, chlorhexidine, chlorocresol, DMDM hydantoin, Dehydroacetic acid, diazolidinyl urea, hydroxybenzoic acid and their salts (parabens), iodopropyl carbamate, imidazolidinyl urea, Phenoxyethanol, salicylic acid and its salts, sorbic acid and their salts, thiomersal; Alcohols, such as. For example, ethanol or isopropanol; Tea tree oil, essential oils, such as. B. Eugenol, thymol or geraniol; Defensins, such as For example, the human β-defensins 1 to 4; and especially for pharmaceutical applications in addition to antibiotics, gyrase inhibitors and growth factor analogues, such as As tetracyclines, β-lactams, glycopeptides, macrolide antibiotics, Sulfonamides or quinolones; Antivirals such. B. acyclovir and its homologues.

In a further preferred embodiment the preparation according to the invention can be used according to the invention Nucleic acids and additionally at least one wound healing, soothing or anti-inflammatory Substance, in particular a substance that is selected under allantoin, urea, azulene, acetylsalicylic acid derivatives, Plant extracts or vitamins, eg. Retinol, α-tocopherol, panthenol, Pantothenic acid or L-ascorbic acid, and the vitamin precursors and derivatives; Antioxidants, such as. B. lycopene, coenzyme Q10, Flavonoids, polyphenols, butylhydroxytoluene or butylhydroxyanisole; Copper salts, such as. Copper chloride or glycyl-L-histidyl-L-lysine copper; as well as especially for pharmaceutical applications additionally also with corticosteroids, such as. B. hydrocortisone, prednisolone or betamethasone, immunosuppressants, such as. Cyclosporin, tacrolimus or pimecrolimus, non-steroidal anti-inflammatory drugs such. B. diclofenac.

The Nucleic acids which can be used according to the invention can be simultaneous or delayed with other substances or forms of therapy are used. Preferred is the same time Application.

The Dosage and duration of use of the present invention Nucleic acids can be determined by one of ordinary skill in the art adapted and varied.

The cosmetic and / or pharmaceutical preparations according to the invention, such as, for example, creams, gels, lotions, alcoholic and aqueous / alcoholic solutions, emulsions, wax / fat compounds, stick preparations, powders or ointments can, depending on the nature of the formulation, be used as auxiliaries and additives mild surfactants, oil bodies, emulsifiers, superfatting agents, bodying agents, thickeners, polymers, silicone compounds, fats, waxes, stabilizers, biogenic agents, film formers, swelling agents, UV light protection factors, antioxidants, hydrotropes, preservatives, solubilizers and the like.

typical Examples of suitable milds, d. H. particularly skin-friendly 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, 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 with linear C ₆ -C ₂₂ fatty alcohols, such as. B. 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, erucyl, erucyl oleate, erucyl behenate and erucyl consideration.

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, for example, propylene glycol, dimerdiol or trimer triol) and / or Guerbet alcohols, triglycerides based on C ₆ -C ₁₀ fatty acids, liquid mono- / di- / triglyceride mixtures 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 linear and / or branched C ₆ -C ₂₂ -alcohols (eg. B. Finsolv ^® TN), linear or branched, symmetrical or asymmetrical dialkyl ethers having 6 to 22 carbon atoms per alkyl group, ring-opening products of epoxidized Fettsäu reestern 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 11 65 574 PS und/oder Mischester von Fettsäuren mit 6 bis 22 Kohlenstoffatomen, 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 (for example sorbitol), alkyl glucosides (eg. Methylglucoside, butylglucoside, laurylglucoside) 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 11 65 574 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 to castor oil 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 _12/18 fatty acid _mono- and diesters of addition products of ethylene oxide with glycerol are made DE 20 24 051 PS known as a refatting agent for cosmetic preparations.

alkyl and / or alkenyl mono- and oligoglycosides, their preparation and their use is known in the art. Your production takes place in particular by reaction of glucose or oligosaccharides with primary alcohols with 8 to 18 carbon atoms. In terms of of the glycoside residue is considered to be both monoglycosides in which cyclic sugar residue is glycosidically linked to the fatty alcohol, as well as oligomeric glycosides with a degree of oligomerization bis preferably about 8 are suitable. The degree of oligomerization is while a statistical mean, the one for such technical products usual homolog distribution lies.

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, Dii sostearoyl Polyglyceryl-3 Diisostearate ( Isolan ^® PDI), Polyglyceryl-3 methylglucose Distearate (Tego Care ^® 450), Polyglyceryl-3 Beeswax (Cera 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 Kokosalkyldimethylammoniumglycinat, N-acylaminopropyl-N, N-dimethylammoniumglycinate, for example Kokosacylaminopropyidimethylammoniumglycinat, 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 may contain 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 be used, the latter also as foam stabilizers serve.

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 in Consideration. Preference is given to a combination of these substances with alkyl oligoglucosides and / or fatty acid N-methylglucamiden same chain length and / or polyglycerol poly-12-hydroxy stearates.

Suitable thickening agents are, for example, Aerosil types (hydrophilic silicic acids), polysaccharides, especially xanthan gum, guar guar, agar agar, alginates and tyloses, carboxymethyl cellulose and hydroxyethyl cellulose, also higher molecular weight polyethylene glycol mono- and diesters of fatty acids, polyacrylates, (eg. B. Carbopol ^® of Goodrich or Synthalens ^® of Sigma), polyacrylamides, polyvinyl alcohol and polyvinyl pyrrolidone, surfactants such as ethoxylated fatty acid glycerides, esters of fatty acids with polyols for example pentaerythritol or trimethylolpropane, fatty alcohol ethoxylates having a narrowed Homo ligen distribution or Alkyloligoglucoside and electrolytes such as sodium chloride and ammonium chloride.

Suitable cationic polymers are, for example, cationic cellulose derivatives, such as. Example, a quaternized hydroxyethylcellulose obtainable under the name Polymer JR 400 ^® from Amerchol, cationic starch, copolymers of diallyl ammonium salts and acrylamides, quaternized vinylpyrrolidone / vinylimidazole polymers, such. B. Luviquat ^® (BASF), condensation products of polyglycols and amines, quaternized collagen polypeptides such as lauryldimony hydroxypropyl hydrolyzed collagen (Lamequat ^® L / Grünau), quaternized wheat polypeptides, polyethylenimine, cationic silicone polymers, such as. B. amidomethicones, copolymers of adipic acid and Dimethylaminohydroxypropyldiethylentriamin (Cartaretine ^® / Sandoz), copolymers of acrylic acid with dimethyldiallylammonium chloride (Merquat ^® 550 / Chemviron), polyaminopolyamides, such as. B. described in the 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. B. dibromobutane with bis-dialkylamines, such as. B. bis-dimethylamino-1,3-propane, cationic guar gum, such as. ^Jaguar® CBS, ^Jaguar® C-17, ^Jaguar® C-16 from Celanese, quaternized ammonium salt polymers, e.g. B. Mirapol ^® A-15, Mirapol ^® AD-1, Mirapol ^® AZ-1 from 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 / methylmethacrylate / tert.butylaminoethylmethacrylate / 2-hydroxypropylmethacrylate 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 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 An 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 come u. a. natural waxes, such. Candelilla wax, 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), crepe fat, ceresin, ozokerite (Earthwax), petrolatum, paraffin waxes, microwaxes; chemically modified Waxes (hard waxes), such as. Montan ester waxes, Sasol waxes, hydrogenated Jojoba waxes and synthetic waxes, such as. B. polyalkylene waxes and polyethylene glycol waxes in question.

When Stabilizers can be metal salts of fatty acids, such as For example, 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.

common 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 its salts and the like Links.

Suitable swelling agents for aqueous phases are montmorillonites, clay minerals, pemulen and alkyl-modified carbopol types (Goodrich). Other suitable polymers or swelling agents can the overview of R. Lochhead in Cosm. Toil. 108, 95 (1993) be removed.

• • 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;
• • Triazinderivate, wie z. B. 2,4,6-Trianilino-(p-carbo-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.

Under UV sun protection factors are, for example, at room temperature, liquid or crystalline organic substances present (sunscreen) to understand that are able to absorb ultraviolet rays and the absorbed energy in the form of longer-wave radiation, eg. B. to give off heat again. UVB filters can be oil-soluble or water-soluble. As oil-soluble substances z. To name, for example:

• • 3-Benzylidencampher or 3-Benzylidennorcampher and its derivatives, eg. B. 3- (4-Methylbenzyli the) campers like in the 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-carbo-2'-ethyl-1'-hexyloxy) -1,3,5-triazine and octyl triazone, as described in U.S.P. EP 0818450 A1 Dioctyl Butamido Triazone or described (Uvasorb HEB ^®);
• • Propane-1,3-dione, such as B. 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 3-Benzylidencamphers, such as. B. 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 197 12 033 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. T805 as titanium dioxide (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 sunscreen filters are the overview of P. Finkel in SOFW Journal 122, 543 (1996) refer to.

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 thereof are amino acids (eg glycine, histidine, tyrosine, tryptophan) and their derivatives, imidazoles (eg urocanic acid) and their derivatives, peptides such as D, L-carnosine, D-carnosine, 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 their derivatives (esters, ethers, peptides, lipids, nucleotides, nucleosides and salts) and sulfoximine compounds (eg buthionine sulfoximines, homocysteinesulfoximine, bithine sulfones, penta, hexa, heptathionine sulfoximine) in very low tolerated dosages (eg pmol to μmol / kg), furthermore (Met all) chasers (eg. Α-hydroxy fatty acids, palmitic acid, phytic acid, lactoferrin), α-hydroxy acids (eg citric acid, lactic acid, malic acid), humic acid, bile acids, 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 their derivatives, vitamin C and derivatives (eg ascorbyl palmitate, Mg ascorbyl phosphate, ascorbyl acetate), tocopherols and derivatives (eg. As vitamin E acetate), vitamin A and De derivatives (vitamin A palmitate) and coniferyl benzoate of benzoin, rutinic acid and derivatives thereof, α-glycosylrutin, ferulic acid, furfurylidene glucitol, carnosine, butylhydroxytoluene, butylated hydroxyanisole, nordihydroguaiacetic acid, nordihydroguiaretic acid, trihydroxybutyrophenone, uric acid and its derivatives, mannose and its 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 derivatives suitable according to the invention (Salts, esters, ethers, sugars, nucleotides, nucleosides, peptides and lipids) of these drugs.

In addition, compounds for suppressing or alleviating skin disorders induced by UV radiation, in particular activators of peroxisome proliferator-activated receptors (PPAR activators), can be added according to the invention, as in US Pat WO 02/38150 to which reference is hereby incorporated by reference.

• • 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 those listed in Appendix 6, Part A and B of the Cosmetics Regulation further substance classes.

Of the Total content of auxiliaries and additives may be 1 to 50, preferably 5 to 40 wt .-% - based on the means - amount. The preparation of the cosmetic and / or pharmaceutical preparation can be caused by usual 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

• CpG-1-PTO, CpG-9-PTO, 20G-PTO and PMA (= positive control) induce the expression of psoriasin in the epidermis after topical Application.

Each 20 μl of a 4 μM oligonucleotide solution (or 50 ng / ml PMA) was applied topically to the epidermis of a full-skin model that was used in the WO 2006/018147 as in " Mewes, KR, Raus, M., Bernd, A., Zoller, NN, Sättler, A., Graf, R .: Elastin expression in a newly developed full-thickness skin equivalent. Skin Pharmacol Physiol 20, 85-95, 2007 After 18 hours' exposure, the full-skin models were fixed and embedded in paraffin, 4 μm sections were deparaffinized, dehydrated and incubated with anti-psoriasin antibodies (Abcam, # ab13680-100) The color proof (see 1 ) was performed using the UltraTech HRP-AEC kit (Coulter, #PN IM2764).

Example 2

• CpG-9-PTO, 20C-PTO, 20G-PTO and PMA (= positive control) induce the expression of HbD-3 in the epidermis after topical Application.

Each 50 μl of a 4 μM oligonucleotide solution (or 50 ng / ml PMA) was applied topically to the epidermis of a full-skin model that was used in the WO 2006/018147 as in " Mewes, KR, Raus, M., Bernd, A., Zoller, NN, Sättler, A., Graf, R .: Elastin expression in a newly developed full-thickness skin equivalent. Skin Pharmacol Physiol 20, 85-95, 2007 After 18 h of exposure, the full-skin models were fixed and embedded in paraffin, 4 μm sections were deparaffinized, dehydrated and incubated with anti-HbD-3 antibodies (Chemicon, # AB3478) The color proof (see 2 ) using the Dako EnVision kit (Dako, # K0597, # K4018).

Example 3

CpG-1 PTO, CpG-9-PTO, 20C-PTO, 20G-PTO induce the expression of psoriasin in the epidermis after systemic administration. The positive control with PMA remained inconspicuous, possibly was the PMA concentration due to the systemic application too low.

For systemic application, the full-skin models ( WO 2006/018147 ; Mewes, KR, Raus, M., Bernd, A., Zoller, NN, Sättler, A., Graf, R .: Elastin expression in a newly developed full-thickness skin equivalent. Skin Pharmacol Physiol 20, 85-95, 2007 ) were supplied with 500 μl of medium containing 4 μM oligonucleotide (or 50 ng / ml PMA). After 18 h of exposure, the full-skin models were fixed and embedded in paraffin. 5 μm sections were deparaffinized, dehydrated and incubated with anti-psoriasin antibodies (Abcam, # ab13680-100).

The color proof (see 3 ) was carried out using the Dako EnVision kit (Dako, # K0597, # K4018.

Example 4

• CpG-1-PTO, CpG-9-PTO, 20C-PTO, 20G-PTO and PMA (= positive control) induce the expression of HbD-3 in the epidermis after systemic Application.

For systemic application, the full-skin models ( WO 2006/018147 ; Mewes, KR, Raus, M., Bernd, A., Zoller, NN, Sättler, A., Graf, R .: Elastin expression in a newly developed full-thickness skin equivalent. Skin Pharmacol Physiol 20, 85-95, 2007 ) were supplied with 500 μl of medium containing 4 μM oligonucleotide (or 50 ng / ml PMA). After 18 h of exposure, the full-skin models were fixed and embedded in paraffin. 5 μm sections were deparaffinized, dehydrated and incubated with anti-HbD-3 antibodies (Chemicon, # AB3478). The color proof (see 4 ) using the Dako EnVision kit (Dako, # K0597, # K4018).

Example 5

• 20C-PTO and 20G-PTO induce the expression of HbD-2 mRNA in in vitro cultured primary keratinocytes.

The cells were treated with 4 μM oligonucleotides (or 20 ng / ml TNFα or 100 ng / ml LPS as positive control). After 18 h, the RNA was extracted, reverse transcribed and the cDNA analyzed for expression of HbD-2 using a real-time PCR instrument (iCycler, Biorad). As reference gene GAPDH was used. The primer sequences used are in " Kippenberger S, Loitsch S, Thaci D, Kaufmann R, Bernd A. Detection of human beta defensin-1 and -2 by RT-competitive multiplex PCR. Arch Dermatol Res. 296: 539-42, 2005 , which is incorporated by reference in its entirety The relative expressions to the untreated control are in 5 specified.

It follows Sequence listing according to WIPO St. 25. This can of the official publication platform of the DPMA become.

QUOTES INCLUDE IN THE DESCRIPTION

This list The documents listed by the applicant have been automated generated and is solely for better information recorded by the reader. The list is not part of the German Patent or utility model application. The DPMA takes over no liability for any errors or omissions.

Cited patent literature

• - DE 10233994 A [0031]
• - DE 10361502 A [0036]
• - DE 19740092 A [0046]
• - DE 1165574 [0058]
• - DE 2024051 [0060]
• - FR 2252840 A [0067]
• EP 0693471 B1 [0075]
• EP 0818450 A1 [0075]
• EP 0694521 B1 [0075]
• DE 19712033 A1 [0077]
• WO 02/38150 [0079]
• WO 2006/018147 [0084, 0085, 0087, 0089]

Cited non-patent literature

• - Steffens R & Leumann CJ: Tricyclo-DNA: A phosphodiester-based DNA analogous to base-pairing properties. J At Chem Soc; 119: 11548-11549, 1997 [0016]
• - Overview of suitable volatile silicones is also found by Todd et al. in Cosm. Toil. 91, 27 (1976). [0069]
• - R. Lochhead in Cosm. Toil. 108, 95 (1993) [0074]
• P. Finkel in SÖFW Journal 122, 543 (1996) [0077]
• - Mewes, KR, Raus, M., Bernd, A., Zoller, NN, Sättler, A., Graf, R .: Elastin expression in a newly developed full-thickness skin equivalent. Skin Pharmacol Physiol 20, 85-95, 2007 [0084]
• - Mewes, KR, Raus, M., Bernd, A., Zoller, NN, Sättler, A., Graf, R .: Elastin expression in a newly developed full-thickness skin equivalent. Skin Pharmacol Physiol 20, 85-95, 2007 [0085]
• - Mewes, KR, Raus, M., Bernd, A., Zoller, NN, Sättler, A., Graf, R .: Elastin expression in a newly developed full-thickness skin equivalent. Skin Pharmacol Physiol 20, 85-95, 2007 [0087]
• - Mewes, KR, Raus, M., Bernd, A., Zoller, NN, Sättler, A., Graf, R .: Elastin expression in a newly developed full-thickness skin equivalent. Skin Pharmacol Physiol 20, 85-95, 2007 [0089]
• Kippenberger S, Loitsch S, Thaci D, Kaufmann R, Bernd A. Detection of human beta defensin-1 and -2 by RT-competitive multiplex PCR. Arch Dermatol Res. 296: 539-42, 2005 [0090]

Claims (23)

Cosmetic and / or pharmaceutical preparation for the treatment of epithelial covering tissue by induction of antimicrobial peptides in the treated epithelial covering tissue, characterized in that it contains nucleic acids. Preparation according to claim 1, characterized in that that the treatment epithelial covering tissue in particular against microbially caused diseases or cosmetic impairments epithelial covering tissue is addressed. Preparation according to claim 1 or 2, characterized that the treatment epithelial covering tissue in particular against Seborrheic skin, impure skin, pustules and comedones as well as against Dandruff is directed. Preparation according to claim 1 or 2, characterized that the treatment epithelial covering tissue in particular against the formation of unpleasant body odor is directed. Preparation according to claim 1 or 2, characterized that the treatment epithelial covering tissue in particular against Diseases in which bacterial pathogens are involved are, preferably against diseases that are selected under: Gonorrhea, Chlamydia infections, Lymphogranulomatosis inguinalis, syphilis, yolk, pinta, borrelia-related Diseases, Ulcus molle, various pyodermas, pyodermias Sweat gland, streptococcal infections, mycobacteriosis, Anthrax, plague and leprosy. Preparation according to claim 1 or 2, characterized that the treatment epithelial covering tissue in particular against Diseases directed by non-bacterial microorganisms be produced, preferably against diseases selected are among: leishmaniasis, trichomoniasis and diseases which fungi and yeasts are involved. Preparation according to claim 1 or 2, characterized that the treatment epithelial covering tissue in particular against virus-related diseases, preferably against diseases that selected from: HIV, measles, rubella, marigold, Papularpupuric gloves and socks syndrome, exanthema subitum, herpes simplex infections, varicella-zoster virus infections, CMV-related Diseases, papillomavirus-related diseases and poxvirus diseases. Preparation according to claim 1 or 2, characterized that the treatment epithelial covering tissue in particular against Diseases directed by bacterial infections aggravate, preferably against diseases selected are below: pathological changes in the fluid and electrolyte balance, inflammation of mucous membranes, such as cheilitis, rhinitis and vulvovaginitis, Eczema, such as seborrheic dermatitis, allergic Eczema, contact dermatitis, xerotic eczema, photoallergic and phototoxic Dermatitis, phytophotodermatitis, radiation dermatitis, stasis dermatitis, Ulcers and erosions resulting from injuries, burns, bullous diseases or ischemia of the skin or mucous membrane, ichthyosis, epidermolysis bullosae, hypertrophic Scars and keloids, skin changes due to intrinsic Aging and photoaging, skin blisters due to mechanical friction, Skin atrophy due to topical use of corticosteroids. Preparation according to claim 1 or 2, characterized that the treatment epithelial covering tissue in particular against Stomach or intestinal diseases, preferably Crohn's disease or against respiratory diseases, especially against cystic fibrosis is directed. Preparation according to one of the preceding claims, characterized in that the nucleic acids are selected are among synthetic nucleic acids, nucleic acids eukaryotic origin, such as nucleic acids from fish roe or wheat germs and nucleic acids of bacterial origin, in particular among nucleic acids from Escherichia coli and Clostridium perfringens. Preparation according to one of the preceding claims, characterized in that the nucleic acids are selected are among high molecular weight bacterial DNA, low molecular weight bacterial DNA, high molecular weight eukaryotic DNA, low molecular weight eukaryotic DNA and oligonucleotides. Preparation according to one of the preceding claims, characterized in that the Oligonu kleotide have a length of 5 to 100, in particular 5 to 70, preferably 10 to 50, preferably 10 to 40 and very particularly preferably from 12 to 30 nucleotides. Preparation according to one of the preceding claims, characterized in that the nucleic acids completely or partially chemically modified. Preparation according to claim 13, characterized that the chemical modification is selected under a) Change in 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 of 2'-deoxyribose; or c) replacement of the strand backbone, in particular replacement of polyester chains based on sugar-phosphate units against carboxamide chains based on amino acid derivatives, such as N- (2-aminoethyl) glycine units, where the a) mentioned under Replacement of phosphodiesters against phosphorothioates is particularly preferred is. Preparation according to claim 13 or 14, characterized that the nucleic acids phosphorothioate phosphodiester mixmere exhibit. Preparation according to one of the preceding claims, characterized in that they contain the nucleic acids in liposomes packed contains. Preparation according to one of the preceding claims, characterized in that the nucleic acids as oligonucleotides having one, two or more CpG motifs. Preparation according to one of the preceding claims, characterized in that the nucleic acids as oligonucleotides which have at least one CpG motif and CpG-A or in particular belong to the CpG-B class. Preparation according to one of the preceding claims, characterized in that the nucleic acids as a superstructure-forming Oligonucleotides are present. Preparation according to claim 19, characterized that the superstructure-forming nucleic acids are selected are among thymine rich or cytosine-rich sequences with a Thymine or cyto sin content of 25% to 100%, preferably 50% to 100%, more preferably 75% to 100%, and most preferably 100%. Preparation according to claim 20, characterized in that that the superstructure-forming nucleic acids are selected are among poly-T homopolymers or poly-C homopolymers. Use of nucleic acids for induction antimicrobial peptides in epithelial cover tissues. Use according to claim 22, characterized in that it takes place in combination with other substances, in particular with those selected from: a) antimicrobial or antiviral substances, in particular p-hydroxybenzoic acid esters, triclosan, hexachlorophene, phenylsalicylic acid, formic acid, benzoic acid and their salts , Benzyl alcohol, benzalkonium chloride, bromochlorophen, bronopol, chlorhexidine, chlorocresol, DM hydantoin, dehydroacetic acid, diazolidinyl urea, hydroxybenzoic acid and its salts, iodopropyl carbamate, imidazolidinyl urea, phenoxyethanol, salicylic acid and its salts, sorbic acid and its salts, thiomersal; Alcohols, such as ethanol or isopropanol; Tea tree oil, essential oils such as eugenol, thymol or geraniol; Defensins, like the human β-defensins 1 to 4; and especially for pharmaceutical applications in addition to antibiotics, gyrase inhibitors and growth factor analogs such. Tetracyclines, β-lactams, glycopeptides, macrolide antibiotics, sulfonamides or quinolones; Antivirals such as acyclovir and its homologs; b) wound-healing, skin-calming or anti-inflammatory substances, in particular allantoin, urea, azulene, acetylsalicylic acid derivatives, plant extracts or vitamins, retinol, α-tocopherol, panthenol, pantothenic acid or L-ascorbic acid, and the vitamin precursors and derivatives; Antioxidants such as lycopene, coenzyme Q10, fiavonoids, polyphenols, butylhydroxytoluene or butylated hydroxyanisole; Copper salts such as copper chloride or glycyl-L-histidyl-L-lysine copper; as well as especially for pharmaceutical applications additionally under corticosteroids, such as hydrocortisone, prednisolone or betamethasone, Immunsup pressives, such as cyclosporin, tacrolimus or pimecrolimus, non-steroidal anti-inflammatory drugs, such as B. diclofenac.