JP2000505790A - Compositions based on squalene and sphingolipids active against bacteria, parasites, protists, fungi and viruses - Google Patents

Abstract

(57) The active ingredient combined from (a) squalene and (b) sphingolipid (c) and, if necessary, an effective amount of one or more α-hydroxycarboxylic acids of formula (I), And their use as antibacterial, antifungal, antiviral and / or protist and / or parasite effective active ingredients.

Description

DETAILED DESCRIPTION OF THE INVENTION Compositions based on squalene- and sphingolipids active against bacteria, parasites, protists, fungi and viruses The present invention relates to compositions active against bacteria, fungi and viruses. As such, it relates to the use of known substances. In a particular embodiment, the invention relates to cosmetic and dermatological preparations comprising such substances. Healthy warm-blooded organisms, especially healthy human skin, have a large number of non-pathogenic microorganisms. This so-called cutaneous microflora is not only harmless, but also exhibits important defenses against opportunistic or pathogenic microorganisms. Bacteria belong to prokaryotic unicellular organisms. Bacteria can be roughly classified according to their shape (spherical, cylindrical, curved cylinder) and according to their cell wall structure (gram-positive, gram-negative). Higher levels of classification also take into account the physiology of the organism. That is, there are aerobic, anaerobic and facultative anaerobic bacteria. Some bacteria are medically important for their pathogenic nature, while others are completely harmless. Substances active against bacteria have been known for quite some time. Although not applicable to all substances with antimicrobial activity, for example, the term “antibiotic” dates back to 1941, the first discovery of penicillin was already acknowledged in 1929. Under the current concept, the metabolic function of warm-blooded animals, such as sick patients, is affected in some ways by the use of antibiotics, so antibiotics are not suitable for all medical treatments, let alone cosmetics. Is not appropriate. Accordingly, one object of the present invention is to enhance the prior art in this regard, i.e., against gram-positive and / or gram-negative bacteria without using substances which affect the health of the user in a particularly unacceptable manner. To provide active substances. Examples of Gram-negative microorganisms are, for example, E. coli, Pseudomonas species, and Enterobacteriaceae, such as, for example, Citrobacter. Gram-positive microorganisms also play an important role in cosmetics and dermatology. In dirty skin, for example, secondary bacterial infections are an important etiology in addition to other factors. One of the most important microorganisms associated with soiled skin is Propionibacterium acnes. Dirty skin and / or comedones impair the good condition of the affected skin, even with mild symptoms. Many people find it necessary to treat such situations, as adolescents have some skin contamination. It was therefore a particular object of the present invention to find substances or combinations of substances which are active against soiled skin or acne Propionibacterium acnes. In a further aspect, the present invention relates to a cosmetic deodorant. Such a composition is intended to eliminate body odor, which is generated when fresh sweat, which is itself odorless, is degraded by microorganisms (especially Gram-positive microorganisms). Customary cosmetic deodorants are based on various active ingredients. Solid compositions such as, for example, deodorant sticks, powders, powder sprays, feminine hygiene products and the like are known and customary, as well as liquid deodorants, for example aerosol sprays, spin-coating etc. . In so-called antiperspirants, astringents (mainly aluminum salts such as aluminum hydroxychloride (aluminum chlorohydrate)) can help reduce sweating, but apart from denaturing the skin's proteins, The substances used in steroids have a dramatic effect on the heat balance in the axillary area depending on the dose and should be used in exceptional cases, at best. It can be used to reduce the bacterial flora on the skin. In the ideal case, only the odor-causing micro-organisms should be effectively reduced, but in practice the entire microflora of the skin is adversely affected. The rate of perspiration itself is unaffected, and in an ideal case the microbial degradation of sweat is temporarily stopped In one composition, an antimicrobial active substance is included. Combinations of astringents are also customary, but the disadvantages of both types of active compounds cannot be completely ruled out in this way .. Finally, although body odor can be blocked by perfume, this method is This is not a way to meet the aesthetic demands of consumers, because the mixture smells rather unpleasant, but generally when the cosmetics contain deodorant active ingredients, as in most cosmetics However, most cosmetic deodorants also contain perfume, which adds to the consumer's acceptability of cosmetics or helps to give the product a special grade. It is not uncommon for cosmetics comprising fragrances to be problematic, especially for cosmetic deodorants, since the active and fragrance ingredients sometimes react with each other to render them inactive. The deodorant should meet the following requirements: 1) It should have a certain deodorant effect. 2) The natural biological processes of the skin must not be adversely affected by deodorants. 3) Deodorants must be safe in case of overdose or when used incorrectly. 4) Should not accumulate on the skin, even after repeated use. 5) Should be easily included in conventional cosmetic compositions. Therefore, another object of the present invention was to develop a cosmetic deodorant which does not have the disadvantages of the prior art. In particular, while deodorants are essentially harmless to the microflora of the skin, they should selectively reduce the microorganisms responsible for body odor. Another object of the invention was to develop cosmetic deodorants which are distinguished by good skin resistance. Under no circumstances should the deodorant active ingredient accumulate on the skin. Yet another object is to develop as many customary cosmetic auxiliaries and additives as possible, especially cosmetic deodorants which are in harmony with the fragrance ingredients which are particularly important in compositions having a deodorant or antiperspirant effect. Met. Yet another object of the present invention was to provide a cosmetic deodorant that is effective over a long period of time, at least on the order of half a day, without noticeable loss of action. Finally, the object of the present invention is to develop a deodorant cosmetic component which is not limited to one or a few special compositions and which can be included as widely as possible in a wide range of cosmetic deodorants. Was to do. The fungal kingdom [Fungi: Latin] is also called the fungal kingdom [μνκηζ = Fungus in Greek] or symbiotic fungi, and belongs to eukaryotes in contrast to bacteria. In contrast to so-called prokaryotes (procytes), eukaryotes are organisms that have a nucleus in which cells (eucyte) are separated from other cytoplasm by nuclear envelopes and nuclear membranes. Cell nuclei contain genetic information stored on chromosomes. Representatives of symbiotic fungi are, for example, yeast (primordial ascomycetes: Protoascomycetes), filamentous fungi (arranged ascomycetes: Plectomycetes), molds (karyophytes: Pyrenomycetes), downy mildew fungi (algae: Phycomycetes) and basidiomycetes Basidiomycetes). Fungi, even Basidiomycetes, do not belong to the plant kingdom, but have plant-like cell walls, cell sap-filled vacuoles, and protoplasmic streams that are easily visible under a microscope like plants. They are free of photosynthetic pigments and are C-heterotrophic. They grow under aerobic conditions and gain energy through the oxidation of organic matter. However, as some representatives, for example, yeast is facultatively anaerobic and can gain energy through fermentation processes. Dermatomycosis is a disease in which certain fungal species, especially dermatophytes, penetrate the skin and hair follicles. Symptoms of dermatomycosis are, for example, small blisters, exfoliation, cracks and erosions, most often with itching and allergic eczema. Dermatomycosis can be divided essentially into four groups: dermatophytosis (eg, epidermophytosis, tinea, microsporosis, tinea), yeast mycosis (eg, radish and pythrosurum) Other fungal diseases caused by the genus (Pityrosporum), Candida infection, Bacillus subtilis, Bush-Buschke disease, Yeast disease, piedra alba, torulopsidosis and hirsutism, fungal mycosis (E.g., aspergillosis, cephalosporosis, alginomycosis and scolariopsis) and systemic mycosis (e.g., chromosome yeast, coccidioidomycosis, and histoplasmosis). Pathogenic and any pathogenic microorganisms include, for example, those from the group of yeasts, Candida species (eg, Candida albicans), as well as those from the family of the genus Pityrosporum. Pityrosporum (Pityrosporum) species, especially egg-shaped Pityrosporum ovale, are seborrhea in the state of versicolor, oily seborrhea and dry seborrhea (these are head seborrhea (= dandruff), eczema-like seborrhea, among others) And pithyrosporum-manifested as folliculitis). It has been debated among the experts that the egg-shaped Pityrosporum ovale is involved in the development of psoriasis. All areas of human skin can be affected by dermatomycosis. Dermatomycosis affects almost all skin, hair and nails. Yeast mycosis also affects mucous membranes and internal organs, but systemic mycosis spreads uniformly throughout the organ system. Areas of the body where moisture and moisture are trapped by clothing, ornaments or shoes are particularly frequently affected. The feet of the athlete are thus the best known and most widespread sites of mycosis. Fungal diseases of the area of the fingernails and toenails (onychomycosis) are also particularly unpleasant. In addition, superinfection of the skin with fungi and bacteria is not uncommon. Primary infections (ie, normal microbial communities of the skin) are present, and large numbers of microbial, but also non-common, one or more common physiological pathogens (eg, staphylococci). -A new infection by a physiological pathogen (eg Candida albicans) can result in a "superinfection" of the affected skin when undesirable factors co-occur. This means that the normal microflora of the skin (or of another organ of the body) grows abnormally through secondary pathogens. If such superinfections progress in favorable conditions, they cause unpleasant skin symptoms (itch, unsightly appearance), depending on the microorganism in question. However, if progressed under adverse conditions, they could lead to extensive skin destruction, and in the worst case, even death of the patient. Superinfections of the type described above are secondary diseases that are often caused, for example, by peaked AIDS. At low microbial counts, microbes that are harmless in any case by themselves, but are also highly pathogenic under certain circumstances, thus overgrow the healthy skin flora. However, in the case of AIDS, other organs in the body are also affected by the superinfection. Such superinfections are also observed in a number of skin disorders such as, for example, atopic eczema, neurodermatitis, acne, seborrheic dermatitis or psoriasis. Many medical and therapeutic measures, such as radiation- or chemotherapy for neoplastic disease, immunosuppression as a medication-induced side effect, or systemic antibiotic treatment also require external chemical or physical agents (eg, Like environmental pollution (smog), it promotes the development of superinfections on external and internal organs, especially the skin and mucous membranes. Superinfections can easily be controlled in individual cases with antibiotics, but such substances have the disadvantage of undesirable side effects. For example, it is common for patients to be allergic to penicillin, and for this reason such treatment is not allowed in this case. Topically administered antibiotics not only eliminate secondary pathogens from the skin flora, but also adversely affect the physiological skin flora, and thus slow the natural healing process. It is an object of the present invention to eliminate the disadvantages of the prior art and to comprise a substance which can be used to cure superinfections, but which has negligible damage to the physiological skin plexus, and the substance To provide a preparation. Protozoa are parasitic unicellular organisms with distinctly separated nuclei that propagate asexually (split into two or four like budding) or sexually (gamametony, gammontony and autologous). is there. They take up nutrients from the environment by osmosis and by phagocytosis or phagocytosis. Most protozoa have asexual, most often motile, living forms (so-called vegetative bodies), but can also form cysts as stationary in unfavorable circumstances. Protozoa can be divided into four groups depending on the type and the means of movement: (a) Mastigophora (flagellate with flagella) (b) Carnivore (Sarcodina) / Rhizopoda (Amoeber movement pattern caused by cytoplasmic protrusion) (c) Sporozoa (Sporozoa) (swelling and gliding movement pattern) (d) Ciliata / Ciliophora (With cilia or flagella). Subtropical and tropic parasitic protozoa are often transmitted by stinging and sucking insects, but also by direct or smear infection, or by the food chain. The following are some protozoonoses of medical and dermatological relevance: trichomoniasis [caused by Trichomonas vaginalis], lamblia flagellosis [lambria intesti Caused by Namb (Lamblia intestinalis), visceral, cutaneous and mucosal leishmaniasis [e.g., Leishmania donovani, L. tropica, L. brasiliensis , L-mexicana, L. diffusa or L. pifanoi, caused by trypanomatosis (caused by various Trypanosoma species), amoebic dysentery and Amoebiasis [eg various Entamoeba species, Jodamoe ba butschlii or Nigeria folleri (caused by Naegleria fowleri), coccidiosis (caused by Isospora belli) and barantidiabosis (caused by balantidium coli). The medical and dermatological phenomena caused by protozoal infections have a considerable, if any, impact on human health. Therefore, these affected sites need to correct this situation. The aim of the present invention was to find active ingredients which act on protists. Parasites can cause disease symptoms (pathogenic parasites) or not (non-pathogenic parasites), at the expense of other organisms (ectoparasites) or in them (endoparasites) A) living, single- or multicellular plants or animals. Parasites also survive as saprophytes, or possibly pure parasites, simply as periodic, temporary or stationary parasites. One to several host organisms are involved in parasite growth, and humans can act as intermediate or ultimate hosts. Examples of parasites of medical and dermatological significance are helminths, which can be classified into trematodes (T rematodae), tapeworms (Cestodae) and nematodes (Nematodae). Helminthoses, which adversely affect human health, include schistosomiasis (caused by Sc histosoma species), infestation of tapeworms in the intestine and other internal organs [eg tapeworms (Taenia ) Species and Echinococcus species), ascariasis (caused by Ascaris lumbricoides), pinworm worm (caused by Enterobium vermi cularis), paragonimiasis Disease (caused by species of Paragonium), filariasis (caused by, for example, Wuchereria bancrofti), and infection by other nematodes (eg, Trichuris trichura) Or caused by Trichinella spiralis). In addition, there are a large number of insect species or cobwebs that parasitize on or in humans and animals and cause medical and dermatological changes in the host organism. Parasitic diseases which in this respect have an adverse effect on human health include, for example, accrodermatitis [caused by cereal mites, such as Pediculoides ventricosus], scabies [Sarcoptes scabii (Sarcoptes scabii) )], Infection by flies and / or fly larvae [e.g., Glossina, Stomoxys, Tabanus, Chrysops, Lucillia, Caused by species of the genus Chrysomya, Cochliamya, Wo hlfartia, Cordyobia or Dermatobia], mosquitoes and / or mosquito larvae [E.g., Aedes, Culex, Anopheles, Phlebotomus, Culicui des, Sumilium or Hemagge Caused by species of the genus Haemagoges], infection by ticks (e.g., Argas persicus and other Argas species, Ornitodorus erraticus and other princess mites (Ornitodorus) ) Species, caused by species of the genus Orobius, Orphous, Rhiphocephalus, Dermacentor, Blood wall mite (Haemaphysalis), True wall mite (Amblyomma), Tick (Ixodes) Diseases caused by insect parasitism (caused by species of Porocephalus), infestation by fleas [e.g., Pulex irr itans, Ctenocephalides canis, Xenopsylla cheopsis] , Pulled by Nosophyllus fasciatus or Sarcopsylla penetrans. Caused by lice [e.g., caused by lice; Phthirius pubis, Pediculosus humanus or Pediculosus capitis], infestation by bed bugs, e.g. Cimex lectularius), Cimex hemipterus, Panstrongylus megistus, Rhodonus prolixus, Triatoma dimidata, Triatoma infestans (Triatoma infest) Or caused by ticks (e.g., caused by Triatoma brasiliensis), as well as by infestation with ticks (e.g., Demodex folliculorum and other Demodex species). Caused by species of the genus Dermamyskus, Glyciphagus domesticus, Pyemotes, species of the Sarcoptes or Trombicula. More importantly, parasites that live on or in human organisms then transmit bacteria, kingdoms, protozoa and viruses, all of which are responsible for the health and well-being of the host organism (eg, humans). The fact is that it has a long-term adverse effect on the condition. Therefore, it was necessary to find active ingredients that are active against parasites and that can improve the medical or dermatological aspects. Therefore, another object of the present invention is to satisfy this need. In contrast to prokaryotic and eukaryotic organisms, viruses [poison in virus = Latin] are biological structures that require host cells for biosynthesis. Extracellular viruses (also called "virions") contain single or double-stranded nucleic acid sequences (DNA or RNA), and protein envelopes (also called "capsids") and, if appropriate, further lipid-containing sheaths. (Envelope). Units consisting of nucleic acids and capsids are also called nucleocapsids. While the classification of classical viruses is based on clinical criteria, current classifications are in most cases classified according to their structure, their morphology, but especially their nucleic acid sequence. The genera of medically important viruses include, for example, influenza virus [family of Orthomyxoviridae], lyssavirus [eg rabies, family of Rhabdoviridae], enterovirus [eg hepatitis A, picorna Viridae (family of the family Picardaviridae)] and hepadnaviruses [eg, hepatitis B, family of the family of hepadnaviridae]. Virucidal agents, or substances that kill viruses, do not exist in a strict sense because the virus does not have its own metabolism. For this reason, there was debate over whether the virus should be classified as an organism. In any case, pharmacological actions that do not damage uninfected cells are difficult. The powerful mechanism of action for fighting viruses is primarily to interfere with their replication, for example by blocking the replication-critical enzymes present in the host cell. Furthermore, release of viral nucleic acids into host cells can be prevented. "Antiviral" or "active against the virus", "viricidal" or synonyms, for the purposes of this disclosure, in each case, whether prophylactically or therapeutically, regardless of the actual mechanism of action of the substance. It is even considered to imply the property of a substance that protects single or multicellular organisms against the deleterious effects of viral infection. However, the prior art lacks substances that are active against viruses and that are harmless or substantially harmless to host organisms. It is therefore an object of the present invention to remedy these drawbacks, i.e. to find substances which, whether prophylactically or therapeutically, effectively protect single or multicellular organisms from the harmful course of viral infection. there were. Surprisingly, (a) squalene and (b) sphingolipids (c) and, where appropriate, an effective amount of one or more of the general formulas Wherein R ′ and R ″ are, in each case independently of one another, (c1) H—, (c2) branched or straight-chain C _1-27 -Alkyl-, (c3) branched or straight chain C substituted by one or more carboxyl groups and / or hydroxyl groups and / or aldehyde groups and / or oxo groups (keto groups) _1-27 -Alkyl-, (c4) phenyl-, (c5) one or more carboxyl groups and / or hydroxyl groups and / or branched and / or straight chain C _1-27 -A-carbon atom of phenyl- or α-hydroxycarboxylic acid substituted by an alkyl group forms a together with R ′ and R ″, and (c6) an unsubstituted 3-7 ring atom or having a Cycloalkyl group, (c7) one or more carboxyl groups and / or hydroxyl groups and / or oxo groups (keto groups) and / or branched and / or linear C _1-27 Is selected from the group consisting of a cycloalkyl group having a 3-7 ring atom, which is substituted with an alkyl group, wherein α-hydroxycarboxylic acid, α-hydroxycarboxylic acid or optionally α-hydroxycarboxylic acid is selected from the group consisting of It has been found that a combination of active substances, which can be in a physiologically acceptable salt and / or ethyl ester and / or methyl ester state, overcomes the disadvantages of the prior art and thus achieves the object. I do. Also according to the invention, combinations of such active substances are used as antibacterial, antifungal, antiviral active substances and / or substances active against protists and / or parasites. A very particular advantage is the use of the active substance combinations according to the invention as active substances acting against Gram-positive bacteria. Squalene (2,6,10,15,19,23-hexamethyl-2,6,10,14,18,22-tetracosahexaene, spinacene) has the structural formula Is the feature. The use of this substance as an antifungal agent against skin diseases is known. Sphingolipids and their use in pharmaceuticals and cosmetics are also known per se. Sphingolipids are based on a sphingosine or phytosphingosine backbone, which is characterized by the following structural formula: The sphingolipids of the invention advantageously have a general backbone Where R ₁ And R _Three Represents, independently of one another, a saturated or unsaturated, branched or straight-chain alkyl group having 1-28 carbon atoms; _Two Is a hydrogen atom, a saturated or unsaturated, branched or straight-chain alkyl group having 1-28 carbon atoms, a sugar residue, a non-esterified or esterified phosphate group. Selected from the group consisting of sulfate groups that are not esterified or esterified by organic groups, and wherein Y represents a hydrogen atom or a hydroxyl group or another heterofunctional group. In accordance with the present invention, active sphingolipids include ceramides, cerebrosides, gangliosides, sphingolipids, among others sphingomyelin, sphingosulfatides and glycosphingosides, and natural and synthetic homologs, examples of which include: Given: Ceramide: R ₁ And R _Three Represents an alkyl group; _Two = H. Sphingolipids: R ₁ And R _Three Represents an alkyl group; _Two Represents a phosphate or organic phosphate group. Sphingomyelin is an organophosphorylated sphingolipid. R _Two If is selected from the group of sugar residues, it is usually distinguished whether it is monoglycosylceramide or di-, tri-, ie generally oligoglycosylceramide is present. Monoglycosylceramide is commonly named cerebroside. Oligoglycosylceramides are mostly named gangliosides. Preferred sphingolipids are ceramides I, II, III and IV, glycosylceramide, lactosylceranod and gangliosides GM1, 2 and 3. The α-hydroxycarboxylic acids according to the invention are advantageously selected from among the following classes of substances: (c2) α-hydroxy-fatty acids, which in turn comprise C _10-18 (C3) α-hydroxy-sugar acids, aliphatic α-hydroxy-fruit acids, (c4) unsubstituted aromatic α-hydroxycarboxylic acids (e.g. Mandelic acid), and (c5) substituted aromatic α-hydroxycarboxylic acids. The α-hydroxy-fatty acid included in item (c2) is represented by the following formula: Α-hydroxycarboxylic acid of the formula and / or Α-hydroxy-isocarboxylic acid of the formula and / or Is particularly preferably selected from the group consisting of: wherein n is a number from 7 to 31 in each case. Substances which can be used with particular advantage for the purposes of the present invention are ₁₆ Α-hydroxycarboxylic acids which represent the form ₁₄ H ₂₉ -A chain attached on an α-carbon atom. It is also advantageous to use such a mixture of aliphatic α-hydroxycarboxylic acids, in particular in the form of a wool wax acid mixture, in an amount of 20-30% by weight, based on the total composition, of the α-hydroxycarboxylic acid. Α-Hydroxy-sugar acids falling under item (c3) are: aldonic acids, such as gluconic acid, galactonic acid, aldaric acids, such as glucaric acid, mucinic acid (or fruit acid tartaric acid, which also falls under the definition of aldaric acid) -Uronic acids, such as glucuronic acid, galacturonic acid, -glyceric acid, are particularly advantageously selected from the group consisting of: The aliphatic α-hydroxy-fruit acids falling under item (c3) are particularly advantageously selected from the group consisting of malic acid, lactic acid, citric acid and tartaric acid. Malic acid (hydroxysuccinic acid) has the following chemical structure: It is characterized by. Lactic acid (2-hydroxypropanoic acid) has the following chemical structure: It is characterized by. Citric acid (2-hydroxy-1,2,3-propanetricarboxylic acid) has the following chemical structure: It is characterized by. Although it is known to use citric acid to buffer cosmetic and / or dermatological preparations, it is also known as an adjuvant to antioxidants in skin and hair cosmetics. Tartaric acid (dihydroxysuccinic acid) has the following chemical structure: It is characterized by. Surprisingly, it has been found that the active substance combinations according to the invention prevent the growth of Gram-positive and Gram-negative bacteria, commensal fungi, protists, parasites and viruses. The active substance combinations according to the invention act as adjuvants, ie have a superadditive effect based on the individual components. In particular, the active substance combinations according to the invention can prevent the growth of yeasts, in particular of the species Pityrosporum, that is to say of egg-shaped Pityrosporum ovale. Furthermore, the active substance combinations according to the invention prevent the development of seborrheic conditions, in particular dandruff, and eliminate the already existing seborrheic conditions, in particular dandruff. In addition, the active substance combinations according to the invention can be used as deodorant active substances in cosmetic deodorants and for the formation of soiled skin, mild acne and acne propinibacterium acne. Well suited enough. Finally, the active substance combinations according to the invention can be used for infection of gram-positive and gram-negative bacteria, commensal fungi, protists, parasites and viruses, especially when they are added in cosmetic and dermatological preparations. It has been found that organic substances, especially such preparations, can be prevented from spoiling. Thus, the present invention provides a symbiotic fungus, characterized in that the active substance combination according to the invention is brought into contact, if appropriate, in a suitable cosmetic or dermatological carrier with an area contaminated with symbiotic fungi. And a method for protecting organic products from infection by commensal fungi, characterized in that the active substance combination is added in an effective amount to these organic products. Thus, the prior art has not at all suggested that the use of the present invention represents an antifungal active ingredient. Also surprising was the fact that the active substance combinations according to the invention are particularly effective against the microbial Pityrosporum ovale and related microorganisms responsible for the development of dandruff. Thus, a preferred embodiment of the present invention is a composition for use against dandruff, such as an anti-dandruff shampoo. According to the invention, the active substance combinations are preferably used in cosmetic or dermatological compositions in a content of from 0.005 to 50.0% by weight, in particular from 0.01 to 20.0% by weight, based on the total weight of the preparation. . The compositions advantageously comprise the active substance combinations according to the invention in amounts of from 0.02 to 10.0% by weight, particularly preferably from 0.02 to 5.0% by weight, in each case based on the total weight of the composition, very particularly preferably. 0.5-3.0% by weight. The active substance combinations according to the invention are customary cosmetic or dermatological compositions, advantageously pump sprays, aerosol sprays, creams, ointments, tinctures, lotions, nail care products (eg nail varnishes, nail polish removers, nail conditioners). Etc. can be included without difficulty. It is also possible to combine the active substance combinations according to the invention with other active substances, for example with other antimicrobial, antifungal or antiviral active substances, which is advantageous where appropriate. It is advantageous to buffer the composition of the invention. A pH range of 3.5-7.5 is advantageous. It is particularly preferred to select within the pH range of 4.0-6.5. The cosmetic and / or dermatological compositions of the present invention can be prepared as usual and treat the skin and / or hair in the sense of a dermatological treatment or in the sense of a care cosmetic. Can be used. However, they can also be used for color cosmetics in makeup products. For use, the cosmetic and / or dermatological compositions of the invention are applied in a sufficient amount to the skin and / or the hair, in the usual manner for cosmetic and dermatological products. Cosmetic and dermatological compositions in the form of sun care products are advantageous. Advantageously, they further comprise at least one UVA filter and / or at least one UVB filter and / or at least one inorganic pigment. The cosmetic preparations according to the invention for protecting the skin against UV radiation can be present in various states, for example, as they are usually used in such preparations. That is, for example, they are solutions, water-in-oil (W / O) emulsions or oil-in-water (O / W) emulsions, or multi-phase emulsions, eg, water-in-oil-in-water (W / O / W), gels, hydrogels It can be a dispersion, a solid stick, or or an aerosol. The cosmetic preparations according to the invention may contain cosmetic auxiliaries, such as preservatives, bactericides, antioxidants, fragrances, defoamers, coloring agents, coloring effects as usually used in such compositions. Pigments, thickeners, surfactants, emulsifiers, emollients, humectants and / or humectants, fats, oils, waxes, or other customary cosmetic composition components (alcohols, polyols, polymers, Blowing agents, electrolytes, organic solvents or silicone derivatives). When the cosmetic or dermatological preparation is a solvent or lotion, the following can be used as solvents:-water or aqueous solutions-oils such as triglycerides of caproic or caprylic acid, preferably castor oil-fats, waxes and Esters of other natural or synthetic fatty substances, preferably fatty acids with low C number alcohols (eg isopropanol, propylene glycol or glycerol), or fatty alcohols with low C number alkanoic acids or with fatty acids; C number alcohols, diols or polyols and their ethers, preferably ethanol, isopropanol, propylene glycol, glycerol, ethylene glycol, ethylene glycol, monoethyl ether, ethylene glycol monobutyl ether Le, propylene glycol monomethyl ether, propylene glycol monoethyl ether, propylene glycol monobutyl ether, diethylene glycol monomethyl ether or diethylene glycol monoethyl ether and analogous products. In particular, mixtures of the abovementioned solvents are used. In the case of alcoholic solvents, water can also be a further component. According to the invention, preferred antioxidants which can be used to advantage are all antioxidants which are suitable for cosmetic and / or dermatological applications. Antioxidants include very low tolerated doses (eg, pmol to μmol / kg) of amino acids (eg, glycine, histidine, tyrosine, tryptophan) and derivatives thereof, imidazole (eg, urocanic acid) and derivatives thereof, peptides (eg, D, L-carnosine, D-carnosine, L-carnosine and derivatives thereof, such as anserine), carotenoids, carotene (eg, α-carotene, β-carotene, lycopene) and their derivatives, lipoic acid and its derivatives (eg, dihydrolipoic acid) Gold thioglucose, propylthiouracil and other thiols such as 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-sulfoximine, homocysteine-sulfoximine, buthionine sulfone, penta-, hexa-, and heptathionine sulfoximine), and (metal) complexing agents (eg, α-hydroxy-fatty acids, Palmitic acid, phytic acid, lactoferrin), α-hydroxy acids (eg, citric acid, lactic acid, malic acid), humic acids, 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), formic acid and their derivatives, ubiquinone and ubiquinol and their derivatives, vitamin C and derivatives (eg, ascorbyl palmitate, Mg-alkolvyl phosphate, ascorbyl Acetate), tocopherols and derivatives (e.g., vitamin E acetate), vitamin A and derivatives (e.g., vitamin A palmitate), and the benzoin resin coniferyl benzoate, rutinic acid and their derivatives, ferulic acid and their derivatives, butylhydroxytoluene, Butylhydroxyanisole, nordihydroguaiac resinic acid, nordihydroguaiaretic acid, trihydroxybutyrophenone, uric acid and its derivatives, mannose and its derivatives Body, zinc and its derivatives (e.g., ZnO, ZnSO _Four ), Selenium and its derivatives (e.g., methionine selenium), stilbene and its derivatives (e.g., stilbene oxide, trans-stilbene oxide), and derivatives (salts, esters, ethers, sugars, nucleotides) of these actives which are stated to be suitable for the present invention. , Nucleosides, peptides and lipids). The antioxidant (one or more compounds) in the preparation is preferably present in an amount of 0.001-30% by weight, particularly preferably 0.05-20% by weight, especially 1-10% by weight, based on the total weight of the preparation. It is. If the antioxidant (s) is vitamin E and / or its derivatives, its individual concentration may be selected from the range of 0.001-10% by weight, based on the total weight of the composition. It is advantageous. If the antioxidant (s) is vitamin A or a vitamin A derivative, or carotene or a derivative thereof, their individual concentrations should be in the range of 0.001-10% by weight, based on the total weight of the composition. It is advantageous to choose from The emulsions according to the invention are advantageous and also comprise, for example, the abovementioned fats, oils, waxes and other fats, as well as water and an emulsifier, as is customarily used in such compositions. The gels of the present invention typically comprise a low C number alcohol (e.g., ethanol, isopropanol, 1,2-propanediol, glycerol) and water or the above oils in the presence of a thickening agent, In the case of alcoholic gels, preferably silicon dioxide or aluminum silicate, and in the case of aqueous-alcoholic or alcoholic gels, preferably polyacrylate. The solid sticks of the present invention comprise, for example, natural or synthetic waxes, fatty alcohols or fatty acid esters. Preferred are lipbalm sticks and deodorant sticks ("Deo-Stick"). Propellants for the cosmetic or dermatological preparations of the invention that can be nebulized from aerosol containers are well known and are readily volatilized and liquefied propellants, such as hydrocarbons (propane, butane, isobutane). Yes, they can be used alone or in combination with one another. Compressed air can also be used to advantage. Of course, those skilled in the art know that there are propellants that are non-toxic in themselves and are in principle suitable for the present invention, but because of the effects of problems on these environments or other concomitant situations, In particular, fluorohydrocarbons and fluorochlorohydrocarbons (FCHC) should not be used. The preparation according to the invention may further comprise a substance which absorbs UV radiation, preferably in the UVB range, in order to provide a cosmetic composition which protects the skin from the whole range of UV radiation, the filter substance The total amount is, for example, 0.1% to 30% by weight, preferably 0.5 to 10% by weight, especially 1 to 6% by weight, based on the total weight of the preparation. They can also be used as sun protection products. UBV filters can be fat-soluble or water-soluble. Examples of liposoluble substances that may be mentioned are: -3-benzylidenecamphor and its derivatives such as 3- (4-methylbenzylidene) camphor, -4-aminobenzoic acid derivatives, preferably 2-ethylhexyl 4- (dimethylamino) Benzoate, amyl 4-dimethylaminobenzoate, esters of cinnamic acid, preferably 2-ethylhexyl 4-methoxycinnamate, isopentyl 4-methoxycinnamate, esters of salicylic acid, preferably 2-ethylhexyl salicylate, 4-isopropyl Benzyl 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, preferred A (p- carbo-2'-ethyl-1'-hexyloxy) -1,3,5-triazine - Ku is 2-ethylhexyl 4-methoxy benzal malonate, 2,4,6-trianilino. Preferred water-soluble substances are: 2-phenylbenzimidazole-5-sulfonic acid and its salts, such as the sodium, potassium or triethanolammonium salts, sulfonic acid derivatives of benzophenone, preferably 2- Hydroxy-4-methoxybenzophenone-5-sulfonic acid and its salts, such as 4- (2-oxo-3-bornylidenemethyl) benzenesulfonic acid, 2-methyl-5- (2-oxo-3-borny Sulfonic acid derivatives of 3-benzylidenecamphor such as (ridenmethyl) sulfonic acid, and salts thereof. Of course, the list of UBV filters that can be used in the present invention is not meant to be limiting. In the preparations according to the invention, it may of course also be advantageous to use UVA filters, which are usually part of cosmetic and / or dermatological preparations. Such substances are preferably derivatives of dibenzoylmethane, especially 1- (4′-tert-butylphenyl) -3- (4′-methoxyphenyl) propane-1,3-dione and 1-phenyl-3- (4′-sopropylphenyl) -propane-1,3-dione. Preparations containing these combinations are also a subject of the present invention. The same amount of UVA filter as described for the UVB filter can be used. The cosmetic and / or dermatological preparations according to the invention can also comprise inorganic pigments usually used in cosmetics to protect the skin from UV radiation. These are oxides of titanium, zinc, iron, zirconium, silicon, manganese, aluminum, cerium and mixtures thereof, and modifications where the oxide is the activator. Pigments based on titanium dioxide are particularly preferred. The amounts given in the above combinations can be used. Cosmetic compositions for hair care include, for example, shampoos, before or after shampooing, before or after perming, or preparations to be used when rinsing hair before or after dyeing or bleaching the hair, blow drying or setting the hair Preparations for dyeing or bleaching, styling and treatment lotions, hair spray or permanent products. Cosmetic preparations comprise the active substances and auxiliaries usually used in such preparations for hair care and hair treatment. Auxiliaries used include preservatives, surfactants, defoamers, emulsifiers, thickeners, fats, oils, waxes, organic solvents, bactericides, fragrances, coloring agents or pigments (to color the hair or the composition itself) To prevent the electrolyte and the hair from being stained with fat. Cosmetic preparations representing shampooing or washing, showering or bathing preparations are preferably at least one anionic, nonionic or zwitterionic surfactant or mixtures thereof, the active substances according to the invention And auxiliaries conventionally used for this purpose. Examples of surfactants which can be used to advantage in the present invention include conventional soaps, such as fatty acid salts of sodium, alkyl sulfates, alkyl ether sulfates, alkane- and alkylbenzene sulfonates, sulfoacetates, sulfobetaines, sarcosinates, amide sulfobetaines. , Sulfosuccinates, sulfosuccinate monoesters, alkyl ether carboxylates, protein / fatty acid condensates, alkyl betaines and amido betaines, fatty acid alkanolamides and polyglycol ether derivatives. The surfactant can be present in the shampoo or cleaning, showering or bathing preparation at a concentration between 1% and 50% by weight. Composition, if the cosmetic or dermatological preparation is in the form of a lotion to be washed off and used, for example, before or after dyeing, before or after shampooing, between two shampoos or before or after perming The substance comprises, for example, an aqueous or aqueous / alcoholic solution, which optionally comprises a surfactant, preferably a nonionic or cationic surfactant, the concentration of which is 0.1 to 10% by weight. And preferably between 0.2 and 5% by weight. The cosmetic or dermatological preparation may be an aerosol with the auxiliaries customarily used for this purpose. Lotion-free cosmetic preparations, especially lotions for hair setting, lotions, styling and treatment lotions used when blowing hair dry are generally aqueous, alcoholic or aqueous-alcoholic solutions, It comprises at least one cationic, anionic, nonionic or zwitterionic polymer or a mixture thereof, and a combination of the active substances according to the invention. The active substance combinations according to the invention used are, for example, between 0.1 and 10% by weight, preferably between 0.1 and 3% by weight. Cosmetic and dermatological preparations for hair treatment and hair care comprising the active substance combinations according to the invention may be non-ionic or anionic emulsions. In addition to water, the nonionic emulsion comprises an oil or a fatty alcohol, which may be, for example, polyethoxylated or polypropoxylated, or may be a mixture of two organic compounds. If appropriate, these emulsions also comprise a cationic surfactant. The anionic emulsion is preferably of the soap type and comprises at least one ethoxylated or propoxylated organic compound of the invention having anionic or nonionic character. Cosmetic and dermatological preparations for hair treatment and hair care can be in the form of gels, which, in addition to the active substance combinations according to the invention and the solvents usually used for this purpose, include organic thickeners, For example, gum arabic, xanthan gum, sodium alginate, cellulose derivatives, preferably methylcellulose, hydroxymethylcellulose, hydroxyethylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose, or inorganic thickeners such as aluminum silicate (eg bentonite), or polyethylene glycol and polyethylene glycol It also comprises a mixture of stearate or polyethylene glycol distearate. This thickener is present in the gel in an amount, for example, between 0.1 and 30% by weight, preferably between 0.5 and 15% by weight. In products intended for hair, the active substance combinations according to the invention are preferably from 0.01% to 10% by weight, in particular from 0.5% to 5% by weight, based on the total weight of the preparation. The following examples are intended to illustrate the invention. All figures are percent by weight unless otherwise stated. Example 1 W / O cream I II liquid paraffin 10.00 10.0 ozokerite 4.00 4.00 white petrolatum jelly 4.00 4.00 vegetable oil 10.00 10.00 wool wax alcohol 2.00 2.00 aluminum stearate 0 .40 0.40 squalene 0.20 0.20 ceramide IV 0.05-ceramide II-0.05-fragrance, preservative Formulation Completely deionized water Add 100.00 to pH 5.5-6. 0 Example 2 W / O Lotion I II Liquid paraffin 5.00 5.00 Isopropyl palmitate 5.00 5.00 Cetyl alcohol 2.00 2.00 Beeswax 2.00 2.00 Ceteareth-20 2.00 2.00 PEG-20 Glycerin stearate 1.50 1.50 Glycerol 3.00 3.00 Squalene 0.30 0.30 Ceramide III 0.10-Glucosylceramide-0.10 Fragrance, preservative Formulation Completely deionized water plus 100. PH 5.5 to 6.0 Example 3 Skin Care Oil I II Cetyl Palmitate 3.00 3.00 Alkyl Benzoate 2.00 2.00 Polyisobutene 10.00 10.00 Squalane 2.00 2.00 Squalene 1.00 1.00 Glucosylceramide 0.05-Lactosyl Ceramide-0.05 Perfume, preservative Formulation Liquid paraffin Add to 100.00 Example 4 Lipstick I II ceresin 8.00 8.00 beeswax 4.00 4.00 carnauba wax 2.00 2.00 white petrolatum jelly 40.00 40.00 hydrogenated castor oil 4.00 4.00 capryl / capric triglyceride 6 0.000 6.00 Squalene 0.50 0.50 Lactosylceramide 0.10-Ganglioside GM1-0.10 Galacturonic acid 0.30 0.30 Fragrance, preservative Formulation Liquid paraffin Add to 100.00 Example 5 Cosmetic Mask I II PEG-50 Lanolin 0.50 0.50 Glyceryl Stearate 2.00 2.00 Sunflower Oil 3.00 3.00 Bentonite 8.00 8.00 Kaolin 35.00 35.00 Zinc Oxide 5. 00 5.00 Squalene 1.50 1.50 Ceramide II 0.10-Ceramide IV-0.10 Tartaric acid 2.00 2.00 Fragrance, preservative Formulation Completely deionized water Add 100.00 pH5 .5-6.0 Example 6 Synthetic Soap I II Sodium Lauryl Sulfate 30.00 30.00 Sodium Sulfosuccinate 10.00 10.00 Cocoyl-Hydrolyzed Potassium 2.00 2.00 Collagen Dimethicone Copolyol 2.00 2.00 Paraffin 2.00 2.00 00 Corn starch 10.00 10.00 Talc 10.00 10.00 Glycerol 3.00 3.00 Squalene 1.50 1.50 Glycosylceramide 0.10-Lactosylceramide-0.10 Fragrance, preservative PH 5.5-6.0 by adding deionized water to 100.00 Example 7 Anti-dandruff shampoo I II Sodium lauryl sulfate 34.00 34.00 Disodium lauryl sulfosuccinate 6.00 6.00 Cocoamidopropyl betaine 10.00 10.00 Glycol distearate 5.00 5.00 Squalene 1.00 1.10 00 Phytoceramide 0.10-Lactosylceramide-0.10 Wool wax acid mixture 0.30 0.30 Flavors, preservatives Formulation Completely deionized water Add 100.00 pH 5.5-6.0 Example 8 Shaving foam I II Stearic acid 7.00 7.00 Sodium lauryl sulfate 3.00 3.00 Stearyl alcohol 1.00 3.00 Glycerol 5.00 5.00 Triethanolamine 3.60 3.60 Squalene 0.500 .50 Ceramide IV 0.05-Glucosylceramide-0.05 Fragrance, preservative Formulation Completely deionized water Add 100.00 pH 5.5-6.0 Example 9 Aerosol spray I II Octyldodecanol 0.50 0.50 Squalene 1.50 1.50 Ceramide III 0.05-Ceramide IV-0.05 Perfume, preservative Formulated ethanol Add 100.00 The resulting liquid phase was transferred to an aerosol container with a propane / butane mixture (2: 7) in a ratio of 39:61. Example 10 Spin-on gel I II 1,3-butylene glycol 2.00 2.00 PEG-40 hydrogenated castor oil 2.00 2.00 hydroxyethylcellulose 0.50 0.50 squalene 0.80 0.80 phytoceramide 0.10-lacto Silceramide-0.10 Lactic acid 0.10 0.10 Perfume, preservative Formulation Completely deionized water Add 100.00 pH 5.5-6.0

──────────────────────────────────────────────────続 き Continued on the front page (51) Int.Cl. ⁷ Identification symbol FI Theme coat ゛ (Reference) A61P 17/00 A61K 31/00 617A A61K 31/035 31/035 31/164 31/16 601 31/194 31 / 19 603 31/688 31/685 603 (72) Inventor Schilever, Järg, Federal Republic of Germany Day-20146 Hamburg Anderhuerbindundsbahn 10 (72) Inventor Borf, Florian Federal Republic of Germany Day-20251 Hamburg・ Fuzmer Shuttle 2

Claims (1)

[Claims] 1. (A) squalene and (b) sphingolipid (c) and, where appropriate, an effective amount of one or more of the general formulas Wherein R ′ and R ″ are in each case independently of one another: (c1) H—, (c2) branched or straight-chain C _1-27 -alkyl—, (c3) one or more carboxyl groups. A branched or straight-chain C _{1-27 -alkyl-} , (c4) phenyl-, (c5) one or more carboxyls substituted by and / or hydroxyl and / or aldehyde and / or oxo (keto) groups. The α-carbon atom of phenyl- or α-hydroxycarboxylic acid substituted by a group and / or a hydroxyl group and / or a branched and / or straight-chain C _1-27 -alkyl group is represented by R ′ and R ″ (C6) an unsubstituted cycloalkyl group having 3-7 ring atoms or a, (c7) one or more carboxyl groups and / or hydroxyl groups and / or oxo groups Keto groups) and / or branched and / or straight-chain C _1-27 - optionally substituted alkyl group, a cycloalkyl group having 3-7 TamakiGen child, is selected from the group consisting of α- hydroxy carboxylic An acid, wherein the α-hydroxycarboxylic acid or optionally the α-hydroxycarboxylic acid can be in a physiologically acceptable salt and / or ethyl ester and / or methyl ester state; Combinations of substances 2. (a) squalene and (b) sphingolipid (c) and, where appropriate, an effective amount of one or more general formulas Wherein R ′ and R ″ are in each case independently of one another: (c1) H—, (c2) branched or straight-chain C _1-27 -alkyl—, (c3) one or more carboxyl groups. A branched or straight-chain C _{1-27 -alkyl-} , (c4) phenyl-, (c5) one or more carboxyls substituted by and / or hydroxyl and / or aldehyde and / or oxo (keto) groups. The α-carbon atom of a phenyl- or α-hydroxycarboxylic acid substituted by a group and / or a hydroxyl group and / or a branched and / or straight-chain C _1-27 -alkyl group together with R ′ and R ″ (C6) an unsubstituted cycloalkyl group having 3-7 ring atoms or a, (c7) one or more carboxyl groups and / or hydroxyl groups and / or oxo groups A cycloalkyl group having a 3-7 ring atom, substituted by a (keto group) and / or a branched and / or straight-chain C _1-27 -alkyl group; A carboxylic acid, which can be in the form of a physiologically acceptable salt and / or an ethyl ester and / or a methyl ester of the α-hydroxycarboxylic acid or optionally the α-hydroxycarboxylic acid. Use of a combination of the active substances of the invention as antibacterial, antifungal, antiviral active substances and / or substances active against protists and / or parasites.