DE19643585A1 - Anti-adhesive formulation containing sphingolipid - Google Patents

Abstract

The use of at least one sphingolipid (I) is claimed as anti-adhesive agent against microorganisms, viruses, parasites and protozoa. Also claimed are (I)-containing formulations with activity as above.

Description

The invention relates to uses of sphingolipids and Preparations containing these substances.

It is already known microorganisms on surfaces by microbicides kill or rinse with cleansers to get their way this way Reduce number on the surface. Both methods have known Disadvantage. So z. B. disinfectants damage the surfaces and Detergents are often insufficient in their effect.

The object of the invention was therefore a gentle and effective method to manage, with which manages the number of microorganisms, viruses, parasites and to minimize or reduce or reduce protozoa on surfaces Prevent microorganisms, viruses, parasites and protozoa Adhere surfaces.

The invention relates to the use of one or more compounds Compounds from the group of sphingolipids as antiadhesive agents, especially against microorganisms, viruses, parasites and protozoa.

With the terms "antiadhesive" and "antiadhesive effect" of Agents of the invention is meant that the adhesion of  Microorganisms, viruses, parasites and protozoa reduced to surfaces or canceled.

The invention also relates to the use of a compound or several compounds from the group of sphingolipids as antiadhesive Active substances against microorganisms, viruses, parasites and protozoa as Component of preparations.

The invention also relates to preparations with a content of one Compound or compounds from the group of sphingolipids with antiadhesive effect against microorganisms, viruses, parasites and Protozoa.

The antiadhesive agents and preparations according to the invention cause that on surfaces only small and no disturbing accumulations of microorganisms, viruses, parasites and protozoa, or they displace already adhering microorganisms, viruses, parasites and Protozoa from the surface and thus reduce their number. You can also be used prophylactically.

The stated objects are achieved according to the invention. The Active ingredients according to the invention have the abovementioned Effects on microorganisms, viruses, parasites and protozoa and are for Treatment of these disorders and diseases suitable.

Sphingolipids and their use in pharmacy and cosmetics are known per se. The basic structure of sphingolipids is sphingosine or phytosphingosine, which are characterized by the following structural formulas:

Sphingolipids according to the invention are advantageously distinguished by the general basic structure

in which R ₁ and R ₃ independently of one another represent saturated or unsaturated, branched or unbranched alkyl radicals of 1 to 28 carbon atoms, R ₂ is selected from the group: hydrogen atom, saturated or unsaturated, branched or unbranched alkyl radicals of 1 to 28 carbon atoms, sugar residues, esterified or unesterified phosphate groups, esterified or unesterified sulfate groups, and Y is either a hydrogen atom, a hydroxy group, or another hetero-functional group.

The sphingolipids which are active according to the invention include the naturally occurring ceramides, cerebrosides, gangliosides, sphingophospholipids, of these in particular the sphingomyelin, sphingosulphatides and glycosphingosides, as well as analogs obtainable by chemical synthesis, of which examples are given below:
Ceramide:

R ₁ and R ₃ represent alkyl radicals, R ₂ = H.

sphingophospholipids:

R ₁ and R ₃ represent alkyl radicals, R ₂ represents a phosphate or Organylphosphatrest.

Sphingomyelin are organylphosphorylated sphingolipids

If R2 is selected from the group of sugar residues, a distinction is usually made as to whether monoglycosylceramides or di-, tri or generally oligoglycosylceramides are present. Monoglycosylceramides are commonly called cerebrosides:

Oligoglycosylceramides are most commonly called gangliosides.

Preferred sphingolipids are ceramide I, II, III and IV, glucosylceramide, lacto sylceramide and the gangliosides GM 1, 2 and 3.

The following substance groups are preferred:
Ceramides, sphingosines, sphinganines, short-chain N-acylceramides, phytosphingosines, sulfatides, neutral sphingolipids and acid glycosphingolipids.

Particular preference is given to the following active compounds according to the invention:
Ceramide:
Ceramide I
Ceramide II
Ceramide III
Ceramide IV
Ceramide V
Ceramide VI
Ceramide VII
Ceramide A
Ceramide B
Neutral sphingolipids and acid glycosphingolipids:
ceramide
galactoside
Ceramide Trihexoside (CTH, Gb3, Gb2CER)
Glucocerobrosid
Galactocerobroside type I
Galactocerobroside Type II
Globo Side
Lactocerobrosid
Lactosylceramide (LacCer, CHD, LC)
NBD Galactocerobrosid
NBD Glucocerobrosid
N-Nervonoyl Cerobroside
N-Oleoyl Cerobrosite
N-palmitoyl cerobrosite
N-stearoyl cerobrosite
Sphingomyelin (stearic, nervous acids)
Sphingomyelin (lignoceric acid)
Cerobrosidsulfat
sulfatides
Asialoganglioside G _M1
Asialoganglioside G _M2
Monosialoganglioside G _M1
Monosialoganglioside G _M2
Monosialoganglioside G _M3
Gangliotetraosylceramide (G _g4 , Asialo G _M1 )
Disialoganglioside G _D1a
Disialoganglioside G _D1b
Disialoganglioside G _D2
Disialoganglioside G _D3
Trisialoganglioside G _T1b
globotriaosylceramide
globotetraosylceramide
Globopentaosylceramid
Tetrasialoganglioside: G _Q1b

Preference is given to sphingolipids, glycosphingolipids and ceramides, in particular the following products for which the trade name and manufacturer are given:

trade name supplier AFR LS Sérobiologiques Ceramides LS Sérobiologiques Dermatin GSL Hormel Lipodermol Sérobiologiques Sphingoceryl LS Sérobiologiques Sphingoceryl LS Powder Sérobiologiques Sphingoceryl Wax LS 2958 B Sérobiologiques Sphingosome AL Sérobiologiques Sphingolipid CB-1 Nikko GlycoCer. Intergen Glycocer.HA Intergen GlycoCer.HALA Intergen Glycoderm Kurt Richter Glycosome Pentapharm Liposomes CLR Kurt Richter Phospholipids FPA Bioiberica Phospholipids FPT Bioiberica Thiosome Kurt Richter

The preparation of the active compounds according to the invention is carried out by the person skilled in the art common, usual methods.

Active ingredients according to the invention are commercially available or known or can be obtained by known methods.  

Preparations, in particular topical preparations, eg. B. cosmetic and dermatological preparations, with the active compounds according to the invention can these z. In amounts of from 0.01 to 25.0% by weight, preferably from 5.0 to 20.0% by weight, but especially from 2.0 to 10 wt .-%, each based on the Total weight of the preparations included. In particular, these apply Quantities also for the individual components of the combinations.

Surprisingly, it has been found that the active compounds according to the invention and preparations containing them, the adhesion, d. H. the assets z. B. the Microorganisms, viruses, parasites and protozoa to adhere to surfaces, reduce their usual number to such areas, or also that no or no significant quantities of Microorganisms, viruses, parasites and protozoa.

Such surfaces are z. B. Organ outer surfaces or organ surfaces, especially from the skin or mucosa and body cavities or Organ cavities, wound cavities or the eye, or the eye socket, the Cornea and the area between eyeball and eyelid.

The healthy warm-blooded organism, especially the healthy one Human skin is associated with a variety of non-pathogenic microorganisms populated. This so-called microflora of the skin is not only harmless to them provides important protection against opportunistic or pathogenic Germs.

Bacteria belong to the prokaryotic unicellular organisms. You can roughly after their shape (sphere, cylinder, curved cylinder) and after the construction their cell wall (gram positive, gram negative) can be distinguished. finer Subdivisions also take into account the physiology of the organisms. So exist aerobic, anaerobic and facultative anaerobic bacteria. Some  Individuals are more medicinal in their capacity as pathogenic germs Meaning, others are completely harmless.

Against bacteria active substances have been known for some time. The Term "antibiotics" for example, not all antimicrobial effective Substances applicable, can be dated to the year 1941, although the first findings on penicillin were already found in 1929. Antibiotics in the modern sense are not for all medical, especially not at all suitable for cosmetic applications, as often the warm-blooded Organism, that is about the diseased patient, when applied to any Is impaired in its metabolic functions.

An object of the present invention was therefore the prior art in enrich this direction, in particular, therefore, substances available which are against Gram-positive and / or Gram-negative bacteria are antiadhesive effect, without that with the application of the substances unacceptable impairment of the health of the user would.

Gram-negative bacteria are, for example, Escherichia coli, Pseudomonas species and enterobacteriaceae, such as Citrobacter.

Gram-positive bacteria also play a role in cosmetics and dermatology. In the case of impure skin, for example, among other influences bacterial secondary infections of etiological significance. One of most important microorganisms associated with impure skin, is Propionibacterium acnes.

Impure skin and / or comedones affect the wellbeing of the Be but even in light cases. Because practically everyone or each Adolescents affected by blemished skin of any severity exists for many people need to remedy this condition.  

A particular object of the present invention, it was a against impure skin or Propionibacterium acnes active substance or Find fabric combination.

The present invention relates in a further embodiment cosmetic Deodorants. Such formulations serve to treat body odor eliminate, which arises when the in itself odorless fresh sweat through especially gram-positive microorganisms is decomposed. The usual Cosmetic deodorants are based on different active principles.

Known and common are both liquid deodorants, for example Aerosol sprays, roll-ons and the like as well as solid preparations, for example, deodorant sticks ("sticks"), powders, powder sprays, intimate cleaners etc.

In so-called antiperspirants can be caused by astringents - predominantly Aluminum salts such as aluminum hydroxychloride (Aluchlorhydrat) - the emergence the sweat be prevented. Apart from the denaturing of Skin proteins, however, access the substances used, depending on their Dosage, drastic in the heat balance of the axillary region and should if necessary in exceptional cases.

By using antimicrobial substances in cosmetic deodorants The bacterial flora on the skin can be reduced. It should ideally only the odor causing microorganisms are effectively reduced. In In practice, it has been found that the entire microflora of the skin can be affected.

The sweat flow itself is not affected, in the ideal case, only the microbial decomposition of sweat temporarily stopped.  

The combination of astringents with antimicrobial substances in one and the same composition is in use. The disadvantages of both However, drug classes are not completely complete in this way remove.

Finally, body odor can also be covered by fragrances, a Method, the least the aesthetic needs of the consumer does justice, as the mixture of body odor and perfume fragrance is more likely unpleasant smells.

However, most cosmetic deodorants, as well as the Most cosmetics overall, perfumed, even if they are deodorant Active ingredients include. Perfuming can also serve the Increase consumer acceptance of a cosmetic product or one Product to give a certain flair.

The perfuming of active ingredient-containing cosmetic agents, in particular Cosmetic deodorants, however, is often problematic because Actives and perfume ingredients occasionally react with each other and can render each other ineffective.

Deodorants should fulfill the following conditions:

• 1) They should cause a reliable deodorization.
• 2) The natural biological processes of the skin must not be affected by the Deodorants are impaired.
• 3) The deodorants must in case of overdose or other not determin harmless to the intended use.
• 4) They should not be on the skin after repeated use accumulate.
• 5) They should work well into common cosmetic formulations to let.

Another object of the present invention was therefore cosmetic To develop deodorants that are not the disadvantages of the prior art respectively. In particular, the deodorants should be the microflora of the skin but the number of microorganisms responsible for the Body odor are responsible, selectively reduce.

Furthermore, it was an object of the invention to provide cosmetic deodorants develop, which are characterized by good skin compatibility. Under no circumstance the deodorizing principles should accumulate on the skin.

Another task was to develop cosmetic deodorants, which with the largest possible variety of conventional cosmetic auxiliary and Additives harmonize, especially with those just in deodorant or antiperspirant formulations of significant perfume ingredients.

Yet another object of the invention was to provide cosmetic deodorants To provide, which over a longer period, in the Order of magnitude of at least half a day, are effective without their Effect noticeably diminishes.

Finally, an object of the present invention was deodorising To develop cosmetic principles that are as universal as possible various forms of administration of cosmetic deodorants incorporated without one or a few specific dosage forms to be committed.

Fungi, also fungi [fungus = Latin fungus], Mycota (mukhζ = Greek fungus) or Mycobionts, count in contrast to the bacteria to the Eukaryotes. Eucaryotes are living things, whose cells (Eucyten) in the Contrary to those of the so-called Procaryonten (Procyten) over one by Nuclear envelope and nuclear membrane separated from the rest of the cytoplasm nucleus feature. The nucleus contains the genetic information stored in chromosomes.  

Representatives of mycobionts include, for example, yeasts (Protoascomycetes), Molds (Plectomycetes), mildew (Pyrenomycetes), the downy mildew (Phycomycetes) and the stem fungi (Basidiomycetes).

Mushrooms, not even the Basidiomycetes, are not plant organisms but like these a cell wall, cell-filled vacuoles and a microscopic highly visible plasma flow. They contain no photosynthetic pigments and are C-heterotrophic. They grow under aerobic conditions and win Energy through oxidation of organic substances. Some representatives, For example, yeasts, however, are optional anaerobes and the Energy production through fermentation processes enabled.

Dermatomycoses are diseases in which certain types of fungi, in particular Dermatophytes, penetrate the skin and hair follicles. The symptoms of Dermatomycoses are, for example, vesicles, exfoliation, rhagades and Erosion, usually associated with itching or allergic eczema.

Dermatomycoses can be divided essentially into the following four groups dermatophytics (eg epidermophytia, favus, microspore, trichophytia), Yeast mycoses (eg, pityriasis and other myrotic pityrosporum-related, Candida infections, blastomycosis, buses Buschke disease, torulosis, Piedra alba, torulopsidosis, trichosporosis), mold mycoses (eg aspergillosis, Cephalosporidosis, phycomycosis and scopular isopidemias), systemic mycoses (e.g. Chromomycosis, coccidiomycosis, histoplasmosis).

The pathogenic and facultative pathogens include, for example from the group of the yeast Candida kinds (eg Candida albicans) and those of the Family Pityrosporuni. Pityrosporum species, in particular Pityrosporum ovale, are for skin conditions such as pityriasis versicolor, seborrhoea in the forms Seborrhoea oleosa and seborrhoea sicca, which are mainly called seborrhoea capitis (= dandruff), seborrheic dermatitis and pityrosporum folliculitis  to blame. Involvement of Pityrosporum ovale The development of psoriasis is discussed by experts.

All areas of human skin can be affected by dermatomycoses become. Dermatophytoses almost exclusively affect the skin, hair and nails. Yeast mycoses can also infect mucous membranes and internal organs, system mycoses regularly extend to whole organ systems.

Particularly often the areas of the body are affected by which Clothing, jewelry or footwear can dampen moisture and heat. So The athlete's foot is one of the best known and most widely used Dermatomycoses. Particularly unpleasant are further fungal diseases of Finger and toenail areas (onychomycoses).

Furthermore, superinfections of the skin by fungi and bacteria are not uncommon.

In case of primary infection, d. h., the normal germination of the skin, entering new infection with high germ counts of one or more often physiological agents, such as staphylococci, but often also Unphysiological pathogen, for example Candida albicans, may be included Coincidence of unfavorable influences a "superinfection" of the afflicted Skin occur. The normal microflora of the skin (or other Körperor goose) is literally overgrown by the secondary pathogen.

Such superinfections may, depending on the particular germ, in favorable cases in unpleasant skin conditions (Itching, unpleasant external appearance) express. In unfavorable However, they can lead to extensive destruction of the skin lead to culminate in the worst case even in the death of the patient.

Superinfections of the aforementioned kind are z. B. the fullscreen of AIDS common secondary diseases. In itself - at least in small  Germ densities - innocuous, but under certain circumstances also pronounced pathogenic germs overgrow in this way the healthy skin flora. at AIDS, however, other body organs are affected by superinfections fen.

Likewise, such superinfections in a variety of dermatological Diseases, eg. Atopic dermatitis, eczema, acne, seborrheic Dermatitis or psoriasis is observed. Also many medical and thera peutic measures, eg. As the radio or chemotherapy of tumors illnesses, caused as a side effect, medically induced Immunosuppression or systemic antibiotic treatment, as well external chemical or physical influences (eg environmental pollution, Smog), promote the appearance of superinfections of the external and internal Organs, in particular the skin and mucous membranes.

Although it is in some cases readily possible, superinfections with Antibiotics, but mostly such substances have that Disadvantage of unpleasant side effects. Often patients are for example allergic to penicillins, which is why appropriate treatment itself would ban in such a case.

Furthermore, topically administered antibiotics have the disadvantage that they Relieve skin flora not only from the secondary pathogen, but also in itself physiological skin flora severely impair and the natural Healing process is slowed down in this way.

Object of the present invention was the disadvantages of the prior Eliminate technology and substances and preparations, such substances containing, by their use Superinfections can be cured using the physiological skin flora no appreciable loss suffers.  

Protozoa are parasitically living unicellular organisms with clearly defined nuclei, which reproduce asexually (by two- or fourfold division as well Budding), or sexually (gameto-, gamonto- and autogamy). The Food intake from the environment takes place by permeation and by Pino or phagocytosis. Most protozoa can live next to vegetative, mostly mobile state forms (so-called trophozoites) under unfavorable circumstances also form cysts as permanent forms.

Depending on the type and mode of transport, protozoa are divided into four different groups:

• (a) Mastigophora (flagellate with flagella)
• (b) Sarcodina / Rhizopoda (amoeboid movement pattern Plasmaausstülpungen)
• (c) Sporozoa (meandering or sliding pattern of movement)
• (d) Ciliata / Ciliophora (Bewimperung or Flagellation)

Parasitic protozoa are found in subtropical and tropical areas often by stinging and sucking insects, but also dirt and Transmission of infection as well as through the food chain.

Some medically and dermatologically relevant protozoonoses are:
Trichomoniasis (caused by Trichomonas vaginalis), Lamblia (caused by Lamblia intestinalis), visceral as well as cutaneous and mucosal leishmaniasis (caused for example by Leishmania donovanii, L.tropica, L. brasiliensis, L-mexicana, L. diffusa or L. pifanoi) , Trypanosomiasis (caused by various Trypanosoma species), amoebic dysentery and amoebasis (caused, for example, by various Entamoeba species, Jodamoeba butschlii or Naegleria fowleri), coccidosis (by Isospora belli) and balantidium (caused by Balantidium coli).

Protozoan-induced medical and dermatological Phenomena affect, in some cases significantly, human well-being.  

There is therefore a considerable need for the persons concerned, this one Conditions to remedy. An object of the present invention was therefore to find effective principles of action against protozoa.

Parasites are monocellular or multicellular plants or animals that live on (= Ectoparasites) or in (= endoparasites) other creatures at their expense nourish with (= pathogenic parasites) or without (apathogenes Parasites) causing disease. The way of life is either aprophytic or purely parasitic, possibly only as Periodic, temporary or stationary parasite. The development of parasites is bound to one or more different host organisms, the Can be an intermediate or final host.

Medicinal and dermatologically important parasites are for example the Helminths, which in turn are found in Trematodae, Cestodae and Nematodae subdivide. Helminths affecting human well-being are, for example, schistosomiasis (caused by Schistosoma species), Tapeworm infestation of the intestine and other internal organs (caused by for example, Taenia species and Echinococcus species), Ascariasis (caused by Ascaris lumbricoides), enterobiasis (caused by Enterobium vermicularis), paragonimiasis (caused by Paragonium species), filariasis (caused for example by Wucheria bancrofti) as well as others Nematode infestation (caused for example by Trichuris trichura or Trichinella spiralis).

In addition, there are a variety of parasitic on or in humans and animals living insects or arachnids, the medical and dermatological changes of the host organisms. In this Respect for the impairment of human well-being Responsible parasitoses include Accrodermatitis (caused by cereal mites, for example Pediculoides ventricosus), scabies (caused by Sarcoptes scabii), fly and / or fly larvae infestation  caused by, for example, Glossina, Stomoxys, Tabanus, Chrysops, Lucilia, Chrysomya, Cochliamya, Wohlfartia, Cordylobia or Dermatobia Species), mosquito and / or mosquito larvae (caused for example by Aedes-Culex, Anopheles, Phlebotomus-Culicuides, Sumilium- or Haemagoges species), tick infestation (caused for example by Argas persicus and other species of argas, Ornithodorus erraticus and others Ornithodorus species, Orobius Rhiphocephalus, Dermacentor, Haemaphysalis, Amblyoma, Ixodes species), Porocephalose (caused by Porocephalus species), Flea infestation (caused by, for example, Pulex irritans, Ctenocephalides canis, Xenopsylla cheopsis, Nosophyllus fasciatus or Sarcopsylla penetrans), lice infestation (caused for example by Phthirius pubis, Pediculosus humanus or Pediculosus captits), bugs caused for example by Cimex lectularius, Cimex hemipterus, Panstrongylus megistus, Rhodnius prolixus, Triatoma dimidata, Triatoma infestans, Triatoma sordida or Triatoma brasiliensis) as well as mite infestation (caused for example by Demodexfolliculorum and other Demodex species and by Dermamyskus species, Glyciphagus domesticus, Pyemotes species, Sarcoptes species or Trombicula species).

It is of additional importance that the on or in the human Organism living parasites in turn re-carriers of bacteria, Mycota, protozoa and viruses can be health and well-being of the host organism, for example of humans, sustainably impair can. There was therefore a need to be effective against parasitosis To find principles of action that the medical or dermatological Appearance are able to improve. To satisfy this need was Therefore, another object of the present invention.

In contrast to the prokaryotic and eukaryotic cellular Organisms are viruses [virus = lat. Poison] biological structures, which contribute to Biosynthesis need a host cell. Extracellular viruses (also called "virions") called) consist of a single- or double-stranded nucleic acid sequence  (DNA or RNA) and a protein coat (called capsid), optionally surrounded by an additional lipid-containing envelope (Envelope). The totality nucleic acid and capsid are also called nucleocapsid. The Classification of viruses was classed according to clinical criteria, nowadays however, mostly according to their structure, their morphology, but especially after the nucleic acid sequence.

Medically important viral genera are, for example, influenza viruses (Family of the Orthomyxoviridae), Lyssaviren (eg rabies, family of the Rhabdoviruses) enteroviruses (eg hepatitis A, family Picornaviridae), Hepadnaviruses (eg hepatitis B, family Hepadnaviridae).

There are no virucidal substances, in the true sense of the term, that kill viruses. because viruses do not have their own metabolism. It became out of this Basically also discussed whether viruses should be classified as living things. Pharmacological intervention without damaging the unaffected cells certainly difficult. Possible mechanisms of action in the fight against the viruses are primarily the disorder whose replication, z. B. by blocking the for replication of important enzymes present in the host cell. Furthermore, can the release of viral nucleic acids into the host cell can be prevented. In the context of the hereby presented disclosure is under terms such as "antiviral" or "effective against viruses", "virucidal" or similar property a substance, a single or multicellular organism harmful consequences of a viral infection, be it prophylactic or therapeu regardless of what the actual mechanism of action in a particular case.

The state of the art, however, lacks effective against viruses Substances which also do not represent the host organism or not damage the dimensions.  

An object of the present invention was thus, this evil situation to remedy, that is, to find substances which are effective on or off multicellular organism from harmful consequences of a viral infection, be it prophylactically or therapeutically.

By the active compounds according to the invention and the thus obtained Preparations are also solved the above objects. The Active ingredients according to the invention are outstandingly suitable for the treatment of states and diseases.

With the active compounds and preparations according to the invention containing them, May attach to the adhesion of all microorganisms, viruses, parasites and protozoa Surfaces are reduced or avoided. This is the case, for example in bacteria, Gram-positive and Gram-negative bacteria, Yeasts, fungi, dermatophytes, viruses, viroids and prions.

In particular, the following microorganisms, viruses, parasites and protozoa for example, and the disorders and diseases caused by them According to the invention, they can be treated particularly well, especially topically become:

1. Gram-positive bacteria

As examples:
Optionally pathogenic and pathogenic Micrococcaceae, especially Staphylococcus epidermidis, e.g. B. in the development of underarm odor and atopic eczema and Staphylococcus aureus as an important pathogen, z. B. in atopic eczema, atopic dermatitis and psoriasis, Corynebacterium spec., Z. B. in the formation of underarm odor, Propionibacterium spec., Z. As in the development of acne and impure skin.

2. Gram-negative bacteria

As examples:
Escherichia coli, e.g. In ulcerative colitis; Pseudomonas aeruginosa, e.g. B. in superinfections of open wounds, z. B. in the abdomen and cystic fibrosis, Enterococcaceae, z. B. in gastrointestinal infections. The active ingredients can be used during flushing and peroral.

3. Yeasts

As examples:
Pityrosporum ovale, z. B. responsible for dandruff and z. In pityriasis versicolor, pityrosporum folliculitis, seborrheic dermatitis, psoriasis, cutaneous and systemic mycoses, in AIDS and related diseases, Candida albicans, e.g. B. responsible for the development of cutaneous candidiasis. The active ingredients can be administered topically, parenterally, but also perorally. Preferably, the intravascular administration, z. B. as an infusion or injection.

4. mushrooms

As examples:
Mucor spec., E.g. B. responsible for Mucor mycoses and thrush; Aspergillus niger, e.g. B. responsible for cutaneous aspergillosis and Cryptococcus neoformans, z. In cryptococidoidosis. The active ingredients can be administered as described for "yeasts".

5. dermatophytes

As examples:
z. B. responsible for the development of dermatophytoses, z. B. athlete's foot. The active ingredients can be administered as described for "yeasts".

6. Viruses

As examples:
Herpes simplex virus type 1 and 2, varicella zoster virus (shingles); Epstein-Barr virus (Pfeiffer glandular fever), cytomegalovirus, wart viruses and papilloma viruses but also other known viruses. The active ingredients can be administered as described in "yeasts".

Protozoa are parasitically living unicellular organisms with a clearly delineated nucleus, the reproduce asexually (by two- or fourfold division as well Budding), or sexually (gameto-, gamonto- and autogamy). The Food intake from the environment takes place by permeation and by Pino or phagocytosis. Most protozoa can live next to vegetative, mostly mobile state forms (so-called trophozoites) under unfavorable circumstances also form cysts as permanent forms.

Depending on the type and mode of transport, protozoa are divided into four different groups:

• (a) Mastigophora (flagellate with flagella)
• (b) Sarcodina / Rhizopoda (amoeboid movement pattern Plasmaausstülpungen)
• (c) Sporozoa (meandering or sliding pattern of movement)
• (d) Ciliata / Ciliophora (Bewimperung or Flagellation)

Parasitic protozoa are found in subtropical and tropical areas often by stinging and sucking insects, but also dirt and Transmission of infection as well as through the food chain.

Some medically and dermatologically relevant protozoonoses are:
Trichomoniasis (caused by Trichomonas vaginalis), Lamblia (caused by Lamblia intestinalis), visceral as well as cutaneous and mucosal leishmaniasis (caused for example by Leishmania donovanii, L. tropica, L. brasiliensis, L-mexicana, L. diffusa or L. pifanoi) , Trypanosomiasis (caused by various Trypanosoma species), amoebic dysentery and amoebasis (caused, for example, by various Entamoeba species, Jodamoeba butschlii or Naegleria fowleri), coccidosis (by Isospora belli) and balantidium (caused by Balantidium coli).

Protozoan-induced medical and dermatological Phenomena affect, in some cases significantly, human well-being. There is therefore a considerable need for the persons concerned, this one Conditions to remedy. An object of the present invention was therefore to find effective principles of action against protozoa.

Parasites are monocellular or multicellular plants or animals that live on (= Ectoparasites) or in (= endoparasites) other creatures at their expense nourish with (= pathogenic parasites) or without (apathogenes Parasites) causing disease. The way of life is either aprophytic or purely parasitic, possibly only as Periodic, temporary or stationary parasite. The development of parasites is bound to one or more different host organisms, the Can be an intermediate or final host.

Medicinal and dermatologically important parasites are for example the Helminths, which in turn are found in Trematodae, Cestodae and Nematodae subdivide. Helminths affecting human well-being are, for example, schistosomiasis (caused by Schistosoma species), Tapeworm infestation of the intestine and other internal organs (caused by for example, Taenia species and Echinococcus species), Ascariasis (caused by Ascaris lumbricoides), enterobiasis (caused by Enterobium vermicularis), paragonimiasis (caused by Paragonium species), filariasis (caused for example by Wucheria bancrofti) as well as others Nematode infestation (caused for example by Trichuris trichura or Trichinella spiralis).

In addition, there are a variety of parasitic on or in humans and animals living insects or arachnids, the medical and dermatological changes of the host organisms. In this Respect for the impairment of human well-being  Responsible parasitoses include Accrodermatitis (caused by cereal mites, for example Pediculoides ventricosus), scabies (caused by Sarcoptes scabii), fly and / or fly larvae infestation caused by, for example, Glossina, Stomoxys, Tabanus, Chrysops, Lucilia, Chrysomya, Cochliamya, Wohlfartia, Cordylobia or Dermatobia Species), mosquito and / or mosquito larvae (caused for example by Aedes-Culex, Anopheles, Phlebotomus-Culicuides, Sumilium- or Haemagoges species), tick infestation (caused for example by Argas persicus and other species of argas, Ornithodorus erraticus and others Ornithodorus species, Orobius Rhiphocephalus, Dermacentor, Haemaphysalis, Amblyoma, Ixodes species), Porocephalose (caused by porocephalus) Species), flea infestation (caused for example by Pulex irritans, Ctenocephalides canis, Xenopsylla cheopsis, Nosophyllus fasciatus or Sarcopsylla penetrans), lice infestation (caused for example by Phthirius pubis, Pediculosus humanus or Pediculosus captits), bugs caused for example by Cimex lectularius, Cimex hemipterus, Panstrongylus megistus, Rhodnius prolixus, Triatoma dimidata, Triatoma infestans, Triatoma sordida or Triatoma brasiliensis) as well as mite infestation (caused, for example, by Demodexfolliculorum and other Demodex Species as well as by Dermamyskus species, Glyciphagus domesticus, Pyemotes- Species, Sarcoptes species or Trombicula species).

It is of additional importance that the on or in the human Organism living pars for its part again carriers of bacteria, Mycota, protozoa and viruses can be health and well-being of the host organism, for example of humans, sustainably impair can. There was therefore a need to be effective against parasitosis To find principles of action that the medical or dermatological Appearance are able to improve. To satisfy this need was Therefore, another object of the present invention. According to the invention, this object has been achieved. The invention Active ingredients and preparations are for the treatment of parasitosis and  Protozoonosen suitable, in particular for the treatment of the above Disorders and diseases.

The use of the active ingredients may be topical, percutaneous, transdermal, parenteral done orally or intravascularly.

Preparations containing active ingredients according to the invention can be topical Preparations, for example, cosmetic and dermatological topical Preparations or else conventional pharmaceutical dosage forms. Deodorants or deodorants are preferred Body cleansing products or personal care products. The active ingredients can but also be included in disinfectants and / or detergents that not just intended for the treatment of the body or the skin, but also for cleaning and disinfecting hard surfaces, medical Materials, appliances, instruments, furniture and walls.

For the body certain cleaning agents, disinfectants, detergents can also be used to treat the skin like the skin topical preparations. But they are preferably used for the treatment of Body cavities, wounds and also the mouth and throat as well as the nose.

The active compounds according to the invention can be prepared by conventional pharmaceutical compatible diluents or carriers and optionally with others Auxiliaries are mixed and administered, for example, orally or parenterally become. They may preferably be administered orally in the form of granules, capsules, pills, Tablets, coated tablets, dragees, syrups, emulsions, suspensions, Dispersions, aerosols and solutions and liquids, or as Zäpfen, vaginal balls or parenteral z. In the form of solutions, emulsions or suspensions. Orally administered preparations may contain one or more additives such as sweeteners, flavoring agents, Dyes and preservatives included. Tablets can be the active ingredient containing mixed with conventional pharmaceutically acceptable auxiliaries, for  Example of inert diluents such as calcium carbonate, sodium carbonate, Lactose and talc, granulating agents and agents that inhibit the disintegration of the tablets when administered orally, such as starch or alginic acid, binders such as Starch or gelatin, lubricants such as magnesium stearate, stearic acid and Talc.

Suitable carriers are, for example, lactose (lactose), gelatin, Corn starch, stearic acid, ethanol, propylene glycol, ethers of Tetrahydrofurfuryl alcohol and water.

The formulations are prepared, for example, by stretching the Active substances with solvents and / or carriers, optionally under Use of emulsifiers and / or dispersants, wherein z. In the case the use of water as a diluent optionally organic Solvent can be used as auxiliary solvent.

The application is carried out in a customary manner, preferably orally or parenterally, especially perlingual or intravenous. In the case of oral use can Tablets, of course, in addition to the mentioned carriers also additives, such as sodium citrate, calcium carbonate and dicalcium phosphate together with various additives, such as starch, preferably potato starch, Gelatin and the like. Furthermore, lubricants such as Magnesium stearate, sodium lauryl sulfate and talc for tabletting be used. In the case of aqueous suspensions and / or elixirs suitable for Oral applications are intended, the active ingredients except with the above excipients with different flavor enhancers or Dyes are added.

In the case of parenteral administration, solutions of the active ingredients may be added Use of suitable liquid carrier materials can be used.  

Capsules may contain the active ingredient as a single ingredient or mixed with one solid diluents such as calcium carbonate, calcium phosphate or kaolin contain. The injectable preparations are also known per se Formulated way.

The pharmaceutical preparations may contain the active ingredient in an amount of 0.1 to 90 weight percent, especially 1-90 wt .-%. Be capsules particularly preferred. Single doses contain the active ingredients preferably in one Amount of 0.1 to 10 g.

The cosmetic and / or dermatological according to the invention Formulations may be composed as usual and for treatment the skin and / or the hair in the sense of a dermatological treatment or a treatment in terms of nourishing cosmetics. But you can also be used in make-up products in the decorative cosmetics or in cosmetic and dermatological cleansing products.

For use, the cosmetic and / or inventive dermatological formulations in the usual for cosmetics and dermatological Applied to the skin and / or hair in sufficient quantity.

Also advantageous are those cosmetic and dermatological preparations, which are in the form of a sunscreen. Advantageously, these contain additionally at least one UVA filter and / or at least one UVB filter and / or at least one inorganic pigment.

The additions of UVA filters and UVB filters or pigments are also available Stabilization of the preparations suitable.

The preparations according to the invention may also preferably comprise substances which absorb UV radiation in the UVB range, wherein the Total amount of filter substances z. B. 0.1 wt .-% to 30 wt .-%, before preferably 0.5 to 10 wt .-%, in particular 1 to 6 wt .-%, based on the total weight of the preparation to make cosmetic preparations  Provide the skin in front of the entire range of ultraviolet Protect radiation. They can serve as sunscreen.

The UVB filters may be oil-soluble or water-soluble. As oil-soluble substances z. To name, for example:

• - 3-Benzylidencampher and its derivatives, for. B. 3- (4-methylbenzylidene) - camphor,
• 4-aminobenzoic acid derivatives, preferably 4- (dimethylamino) benzoic acid acid (2-ethylhexyl) ester, 4- (dimethylamino) benzoic acid amyl ester;
• Esters of cinnamic acid, preferably 4-methoxycinnamic acid (2-ethylhexyl) ester, 4-methoxycinnamate;
• Esters of salicylic acid, preferably 2-ethylhexyl salicylate, Salicylic acid (4-isopropylbenzyl) ester, salicylic acid homomenthyl ester;
• Derivatives of benzophenone, preferably 2-hydroxy-4-methoxybenzophenone, 2-hydroxy-4-methoxy-4'-methylbenzophenone, 2,2'-dihydroxy-4-methoxybenzophenone;
• Esters of benzalmalonic acid, preferably 4-methoxybenzalmalonate (2-ethylhexyl) ester;
• 2,4,6-trianilino (p-carbo-2'-ethyl-1'-hexyloxy) -1,3,5-triazine

As water-soluble substances are advantageous:

• 2-phenylbenzimidazole-5-sulfonic acid and its salts, eg. For example, sodium, Potassium or triethanolammonium salts,
• - Sulfonic acid derivatives of benzophenones, preferably 2-hydroxy-4-methoxybenzophenone-5-sulfonic acid and their salts;
• - Sulfonic acid derivatives of 3-Benzylidencamphers, such as. B. 4- (2-oxo-3-boron nylidenemethyl) benzenesulfonic acid, 2-methyl-5- (2-oxo-3-bomylidene methyl) sulfonic acid and its salts.

The list of said UVB filters, which find use according to the invention can, of course, not be limiting.  

It may also be advantageous in formulations according to the invention UVA filters commonly used in cosmetic and / or dermatological applications preparations are included. Such substances are present preferably derivatives of dibenzoylmethane, in particular 1- (4'- tert-butylphenyl) -3- (4'-methoxyphenyl) propane-1,3-dione and 1-phenyl-3- (4'-iso propylphenyl) propan-1,3-dione. Also preparations containing these combinations contain, are the subject of the invention. It can be the same amounts UVA filter substances are used, which for UVB filter substances were called.

Cosmetic and / or dermatological preparations according to the invention may also contain inorganic pigments commonly used in the art Cosmetics are used to protect the skin from UV rays. there are oxides of titanium, zinc, iron, zirconium, silicon, Manganese, aluminum, cerium and mixtures thereof, as well as modifications where the oxides are the active agents. It is particularly preferred pigments based on titanium dioxide. It can be for the above Combinations mentioned quantities can be used.

Cosmetic and dermatological preparations according to the invention, also z. As to protect the skin from UV rays, can in various forms present as z. B. usually for this type of preparations be used. So they can z. B. a solution, an emulsion of the type Water-in-oil (W / O) or oil-in-water (O / W), or a multiple Emulsions, for example of the water-in-oil-in-water (W / O / W) type, a gel, a hydrodispersion, a solid stick or an aerosol.

The cosmetic preparations according to the invention can be cosmetic Contain excipients, such as those commonly used in such preparations be, for. Preservatives, bactericides, antioxidants, perfumes, agents for preventing foaming, dyes, pigments that have a coloring Have thickening agents, surface-active substances, emulsifiers, softening substances, moisturizing and / or moisturizing substances,  Fats, oils, waxes or other common ingredients of a cosmetic Such as alcohols, polyols, polymers, foam stabilizers, electrolytes, organic solvents or silicone derivatives.

If the cosmetic or dermatological preparation is a solution or lotion, the solvent used may be:

• - water or aqueous solutions;
• - Oils, such as triglycerides of capric or caprylic acid, but preferably Castor oil;
• - fats, waxes and other natural and synthetic fats, preferably esters of fatty acids with lower C-number alcohols, e.g. B. with Isopropanol, propylene glycol or glycerol, or esters of fatty alcohols with Alkanoic acids of low C number or with fatty acids;
• Alcohols, diols or polyols of low C number, and their ethers, preferably ethanol, isopropanol, propylene glycol, glycerol, ethylene glycol, Ethylene glycol monoethyl or monobutyl ether, propylene glycol monomethyl,
• monoethyl or monobutyl ether, diethylene glycol monomethyl or monoethyl ether and analog products.

In particular, mixtures of the abovementioned solvents used. For alcoholic solvents, water can be another Be part of it.

According to the invention as favorable antioxidants all for cosmetic and / or dermatological applications suitable or common Antioxidants are used.

Advantageously, the antioxidants are selected from the group consisting of amino acids (eg, glycine, histidine, tyrosine, tryptophan) and their derivatives, imidazoles (eg, urocanic acid) and derivatives thereof, peptides such as D, L-carnosine, D- Carnosine, L-carnosine and their derivatives (eg anserine), carotenoids, carotenes (eg α-carotene, β-carotene, lycopene) and their derivatives, lipoic acid and derivatives thereof (eg dihydrolipoic acid), Aurothioglucose, propylthiouracil and other thiols (eg thioredoxin, glutathione, cysteine, cystine, cystamine and their glycosyl, N-acetyl, methyl, ethyl, propyl, amyl, butyl and lauryl, palmitoyl) , Oleyl, γ-linoleyl, cholesteryl and glyceryl esters) and their salts, dilauryl thiodipropionate, distearyl thiodipropionate, thiodipropionic acid and derivatives thereof (esters, ethers, peptides, lipids, nucleotides, nucleosides and salts) and sulfoximine compounds (eg buthionine sulfoximines, Homocysts insulfoximine, buthionine sulfones, penta-, hexa-, heptathioninesu lfoximin) in very low tolerated dosages (eg. Pmol to μmol / kg), furthermore (metal) chelators (for example α-hydroxyfatty acids, palmitic acid, phytic acid, lactoferrin), α-hydroxy acids (for example citric acid, lactic acid, malic acid), humic acid, Bile acids, biliary 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, vitamin E acetate), vitamin A and derivatives (vitamin A palmitate), and benzylic resin, rutinic acid and derivatives thereof, ferulic acid, and conyanyl benzoate their derivatives, butylhydroxytoluene, butylhydroxyanisole, nordihydroguaiacetic acid, Nordihy droguajaretsäure, trihydroxybutyrophenone, uric acid and its derivatives, mannose and its derivatives, zinc and its derivatives (eg ZnO, ZnSO ₄ ) selenium and its derivatives ( eg selenomethionine), stilbenes and their derivatives (e.g. B. stilbene oxide, trans-stilbene oxide) and the present invention suitable derivatives (salts, esters, ethers, sugars, nucleotides, nucleosides, peptides and lipids) of these drugs.

The amount of antioxidants (one or more compounds) in the Preparations are preferably from 0.001 to 30% by weight, more preferably 0.05-20 wt .-%, in particular 1-10 wt .-%, based on the total weight the preparation.  

If vitamin E and / or its derivatives, the antioxidant (s) is advantageous, their respective concentrations from the range of 0.001-10 wt%, based on the total weight of the formulation choose.

If vitamin A, or vitamin A derivatives, or carotenes or their derivatives the one or more antioxidants are advantageous, their respective Concentrations in the range of 0.001-10 wt .-%, based on the Total weight of the formulation to choose.

Emulsions of the invention are advantageous and contain z. As the mentioned Fats, oils, waxes and other fatty substances, as well as water and an emulsifier, as commonly used for such type of formulation.

Gels according to the invention usually contain lower C-number alcohols, z. As ethanol, isopropanol, 1,2-propanediol, glycerol and water or a above-mentioned oil in the presence of a thickening agent which is oily Alcoholic gels preferably silica or an aluminum silicate, at aqueous-alcoholic or alcoholic gels preferably a polyacrylate.

Solid pins according to the invention contain z. Natural or synthetic Waxes, fatty alcohols or fatty acid esters. Preference is given to lip balms and deodorant sticks ("deodorant sticks").

As a propellant for inventive sprayable from aerosol containers Cosmetic or dermatological preparations are the usual known volatile, liquefied propellant, z. B. hydrocarbons (propane, Bu tan, isobutane), used alone or in admixture with each other can be. Also, compressed air is advantageous to use.

Of course, the person skilled in the art knows that there are nontoxic propellants per se which basically suitable for the present invention, but nevertheless because of its detrimental effect on the environment or other accompanying circumstances should be waived, especially fluorocarbons and fluorochloro hydrocarbons (CFCs).  

The preparations according to the invention may also preferably comprise substances which absorb UV radiation in the UVB range, wherein the Total amount of filter substances z. B. 0.1 wt .-% to 30 wt .-%, before preferably 0.5 to 10 wt .-%, in particular 1 to 6 wt .-%, based on the total weight of the preparation to make cosmetic preparations Provide the skin in front of the entire range of ultraviolet Protect radiation. They can also serve as sunscreen.

Cosmetic preparations according to the present invention may also contain inorganic pigments, which are commonly used in cosmetics for Protecting the skin from UV rays can be used. It refers to Oxides of titanium, zinc, iron, zirconium, silicon, manganese, aluminum, Cers and mixtures thereof, as well as modifications in which the oxides of the active agents are. Particularly preferred are pigments on the Base of titanium dioxide.

Cosmetic preparations for hair care are For example, to shampoo, preparations that rinse the Hair before or after shampooing, before or after Perming treatment, before or after coloring or decolorization of the hair be used to prepare hair or hair, Preparations for dyeing or decolorising to a hairdressing and Treatment lotion, a hair lacquer or permanent waving agent.

The cosmetic preparations contain active ingredients and auxiliaries, as they are Usually for this type of preparations for hair care and Haarbe be used.

As auxiliaries serve preservatives, surface-active substances, Substances for preventing foaming, emulsifiers, thickeners, Fats, oils, waxes, organic solvents, bactericides, perfumes, dyes or pigments whose job it is to do the hair or the preparation itself coloring, electrolytes, preparations against the greasing of the hair.

Cosmetic preparations containing a shampoo or a washing, Shower or bath preparation, preferably contain at least  an anionic, nonionic or amphoteric surfactant or Mixtures thereof, at least one ethoxylated or propoxylated organic compound in an aqueous medium and adjuvants such as Usually used for this. The surfactant can be used in a concentration between 1 wt .-% and 50 wt .-% in the Shampoo, or the washing, shower or bath preparation, available.

Is the cosmetic or dermatological preparation in the form of a lotion before, the rinsed out and z. B. before or after decolorization, before or after Shampooing, between two shampooing steps, before or after Perming treatment is applied, so it is z. B. order aqueous or aqueous-alcoholic solutions, optionally contain surface-active substances, preferably non-ionic or cationic surfactants whose concentration is between 0.1 and 10% by weight, preferably between 0.2 and 5% by weight. These cosmetic or dermatological preparation can also be an aerosol with the represent commonly used tools.

A cosmetic preparation in the form of a lotion that is not rinsed out, in particular, a lotion for inserting the hair, a lotion when blown hair is used, a hairdressing and treatment lotion, poses in the generally an aqueous, alcoholic or aqueous-alcoholic solution and contains at least one cationic, anionic, nonionic or amphoteric polymer or mixtures thereof.

Cosmetic and dermatological preparations for the treatment and care of Hair may be in the form of emulsions other than non-ionic or non-ionic are anionic type. Non-ionic emulsions contain oils in addition to water or fatty alcohols which are, for example, polyethoxylated or polypropoxylated can, or mixtures of the two organic components. These Emulsions optionally contain cationic surfactants. Anionic emulsions are preferably of the soap type and are included at least one ethoxylated or propoxylated organic according to the invention Compound of anionic or non-ionic character.  

Cosmetic and dermatological preparations for the treatment and care of Hair may be present as gels, in addition to at least one alkylated hydroquinone according to the invention and usually solvents used nor organic thickeners, eg. B. Gum arabic, xanthan gum, sodium alginate, cellulose derivatives, preferably methylcellulose, hydroxymethylcellulose, hydroxyethylcellulose, Hydroxypropylcellulose, hydroxypropylmethylcellulose or inorganic Thickener, z. As aluminum silicates such as bentonites, or a Mixture of polyethylene glycol and polyethylene glycol stearate or distearate, contain. The thickener is in the gel z. B. in an amount between 0.1 and 30 wt .-%, preferably between 0.5 and 15 wt .-%, included.

Unless otherwise stated, quantities, Percentages and parts by weight, especially on the Total weight of the respective mixture or preparation.

The invention also provides the use of the invention Active ingredients for the preparation of preparations, in particular pharmaceutical Preparations for the treatment of the specified disorders or diseases.

The following examples are intended to illustrate the embodiments of the present invention clarify. The numerical values given are% by weight.  

W / O Cream

W / O Cream

O / W Lotion

O / W Lotion

skin oil

skin oil

lipstick

lipstick

care mask

care mask

syndet

syndet

Anti dandruff shampoo

Anti dandruff shampoo

shaving cream

shaving cream

aerosol spray

aerosol spray

Roll-on gel

Roll-on gel

Claims (6)

1. Use of one or more compounds from the group the sphingolipids as antiadhesive agents against microorganisms Viruses, parasites and protozoa. 2. Use of one or more compounds from the group the sphingolipids as antiadhesive agents against microorganisms, Viruses, parasites and protozoa as a constituent of preparations. 3. preparations containing one or more compounds Compounds from the group of sphingolipids with antiadhesive effect against microorganisms, viruses, parasites and protozoa. 4. uses and preparations according to claim 1-3, characterized characterized in that as sphingolipids one or more of the active ingredients Cerebrosides, gangliosides, sphingophospholipids, of these in particular the Sphingomyelin, Sphingosulfatide, Ceramide, Sphingosine, Sphinganine, short-chain N-acylceramides, phytosphingosines, sulfatides, neutral sphingolipids and acid glycosphingolipids are chosen. 5. Preparations according to claims 1-4, characterized in that it is are topical preparations. 6. Use of the active compounds according to claim 1-4 as active ingredients in Deodorants.