DE19503423A1 - Antiadhesive agents - Google Patents

Abstract

The invention concerns the use of a compound or a number of compounds from the group of the carbohydrates or carbohydrate derivatives as anti-adhesive active principles directed against micro-organisms, parasites and protozoa.

Description

The invention relates to a use of carbohydrates or Carbohydrate derivatives, 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 To create a method that manages to reduce the number of microorganisms Minimize or reduce surfaces or prevent them Adhere microorganisms to surfaces.

The invention relates to the use of one or more compounds Compounds from the group of carbohydrates or carbohydrate derivatives as antiadhesive agents to microorganisms.

With the terms "antiadhesive" and "antiadhesive effect" of Agents of the invention is meant that the adhesion of Microorganisms on surfaces is reduced or suspended.  

The invention also relates to the use of a compound or several compounds from the group of carbohydrates or carbohydrate derivatives as antiadhesive agents to microorganisms as Component of preparations.

The invention also relates to preparations with a content of one or more compounds from the group of Carbohydrates or carbohydrate derivatives with antiadhesive effect towards microorganisms.

The antiadhesive agents and preparations according to the invention can be used prophylactically and cause itself on surfaces only still small and no disturbing accumulations of microorganisms or displace already adherent microorganisms from the surface and thus reduce their number.

Well-suited carbohydrates or "carbohydrate derivatives" that are linguistically in short also under the name "carbohydrates" are to fall are Sugars and substituted sugars or sugar residues containing compounds.

Preference is given to the following active substances with sugar structures:

• 1. Monosaccharides
  Highly suitable monosaccharides are z. As tetroses, pentoses, hexoses and heptoses. Preference is given to pentoses and hexoses. The ring structures include furanoses and pyranoses, including both D and L isomers, as well as α and β anomers.
• 2. Disaccharides
  Well suitable disaccharides are for. B. the disaccharides formed by binary linkages of the above monosaccharides. Linkage can occur as α- or β-glycosidic linkage between the two subunits. Sucrose, maltose, lactobiose are preferred.
• 3. Oligosaccharides
  Highly suitable oligosaccharides consist of several, for. B. 2-7 sugar units, preferably the sugars described under 1 and 2, in particular from 2 to 4 units in the known, formed by condensation bonding forms and as mentioned above. Particularly preferred oligosaccharides are, in addition to the disaccharides, the trisaccharides.
• 4. Aminosugar
  Highly suitable are mono-, di- and oligosaccharides, in particular as described above, with one or more amino groups which may be acylated, in particular acetylated. Preference is given to ribosylamine; N-acetylglucosamine and N-galactosylamine.
  Furthermore, sugar esters of organic or inorganic acids are advantageously used, for example sugar phosphates, sugar esters with carboxylic acids or sulfated sugars, especially esters of the sugars described above.
• 5. Preferred sugar esters of phosphoric acid are glucose-1-phosphate; Fructose-1-phosphate or glucose-6-phosphate.
• 6. Preferred esters of sugars and carboxylic acids are with carboxylic acids the chain length C₁ to C₂₄, z. B., for example Cetearylglucosid (Fa. Seppic: Montanol 68); Caprylyl / caprylglucoside (Seppic: Oramix CG-110);  Decylglucoside (Seppic: Oramix NS-10), but especially the Sugar acetates, preferably the above sugar.
• 7. Also preferred are the sugar ethers of sugars, in particular the above sugar, with alcohols of chain length C₁ to C₂₄.
• 8. Continue with z. As the reaction products of sugars with ethylene oxide and / or propylene oxide, preferably with the above sugars. Suitable are E / O-grade from one to 40 ether units.
• 9. glycolipids
  Preferred glycolipids are glycosphingolipids, especially ceramides, cerebrosides, gangliosides and sulfatides.
• 10. Polysaccharides (natural and synthetic origin)
  The polysaccharides can be unbranched or branched, and both the homopolysaccharides and the heteropolysaccharides, in each case in particular with such sugars as described under 1 to 7, are suitable. Preferred polysaccharides are starch, glycogen, cellulose, dextran, tunicin, inulin, chitin, in particular chitosans, alginic acid and alginates, vegetable gums, body slimes, pectins, mannans, galactans, xylans, arabans, polyoses, chondroitin sulfates, heparin, hyaluronic acid and glycosaminoglycans, hemicelluloses, substituted cellulose and substituted starch, in particular in each case the hydroxyalkyl-substituted polysaccharides.

Particularly suitable are amylose amylopectin, xanthan, α-, β- and γ-dextrin.

The polysaccharides can, for. B. from 4 to 1 000 000, in particular 10 to 100,000 monosaccharides exist. Preferably, each such Chained chain lengths that ensure that the active ingredient in the respective Preparation soluble or to be incorporated into it.  

The active compounds according to the invention can be used individually. It is but also possible, two, three or more active ingredients together too use. In particular, monosaccharides and oligosaccharides be combined, where in each case one saccharide but also two or three or several sugars can be chosen. Together with the above mentioned sugars or combinations thereof may be advantageous Polysaccharide or more polysaccharides can be used.

The following active compound combinations a) -f) are particularly preferred:

• a) fucose,
  Raffinose and
  galactose
• b) glucose 6-phosphate,
  Mannose-6-phosphate and
  mannose
• c) raffinose,
  N-acetyl-glucosamine, and
  fucose
• d) mannose,
  Rhamnose and
  fucose
• e) galactose,
  N-acetyl-glucosamine and
  fucose
• f) mannose,
  Raffinose and
  galactose

Also preferred are the individual components of the combinations and with two components to be formed two combinations of the three Active ingredients in each case a triple combination.

Advantageously, each with a sugar or more sugars the group of monosaccharides and / or oligosaccharides one or several sugars from the group of sugar phosphates and / or the Amino sugar and acetylamino sugar are combined.

In the combinations, the active ingredients z. B. with the same Weight amounts or in the weight ratio to 1: 10 or 10: 1 be used.

Preparations, in particular topical preparations, eg. B. cosmetic and dermatological preparations containing the active compounds according to the invention can these z. B. in amounts of 0.01 to 99 wt .-%, preferably 1 to 50 Wt .-%, but especially 5 to 20 wt .-%, each based on the Total weight of the preparations included.

Surprisingly, it has been found that the active compounds according to the invention and preparations containing them, the adhesion, d. H. the fortune of Micro-organisms adhere to surfaces, reduce, so that their usual number reduced to such areas, or even that no or no longer detect significant levels of microorganisms.

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.  

With the active compounds and preparations according to the invention, these The adhesion of all microorganisms to surfaces can be reduced or avoided. This is the case with bacteria, for example although in Gram-positive and Gram-negative bacteria, yeasts, fungi, Dermatophytes, viruses, viroids and prions.

The following microorganisms, for example, and those by them caused disorders and diseases can according to the invention particularly good, in particular to be treated topically:

• 1. Gram-positive bacteria
  As examples:
  Ficultatively 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 in cyctic 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".

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. The However, active ingredients can also be used in disinfectants and / or  Cleaning products should not be included just to treat the body or the skin are determined, but also for cleaning and disinfecting hard surfaces, medical materials, devices, instruments, Furniture and walls.

For the body certain cleaning agents, disinfectants, detergents can also be used for the treatment of the skin as already the topical preparations. But they are preferably for 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 other adjuvants and, for example, orally or parenterally be administered. They may preferably be administered orally in the form of granules, Capsules, pills, tablets, film-coated tablets, dragees, syrups, emulsions, Suspensions, dispersions, aerosols and solutions and liquids, or as Zäpfen, vaginal balls or parenteral z. B. in the form of Solutions, emulsions or suspensions. Orally too Administering preparations may include one or more supplements such as Sweetening, flavoring, coloring and preservative agents contain. Tablets can be the active ingredient with usual pharmaceutical containing compatible additives, for example inert Diluents such as calcium carbonate, sodium carbonate, lactose and talc, Granulating agents and agents that inhibit the disintegration of the tablets in the case of oral Promote administration 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 case of oral use Tablets can, 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 you can Lubricants such as magnesium stearate, sodium lauryl sulfate and talcum for Tableting be used. In the case of aqueous suspensions and / or Elixirs intended for oral use may contain 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 be used using suitable liquid carrier materials.

Capsules may contain the active ingredient as a single ingredient or mixed with a solid diluent such as calcium carbonate, calcium phosphate or Containing kaolin. The injectable preparations are also in themselves formulated in a known manner.

The pharmaceutical preparations may contain the active ingredient in an amount of 0.1 to 90 weight percent, especially 1-90 wt .-%. capsules are particularly preferred. Single doses contain the active substances preferably in an 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 dermatological treatment or a treatment in terms of nourishing cosmetics. You can but also used in make-up products in decorative cosmetics or in the 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 included this additionally at least one UVA filter and / or at least one UVB filter and / or at least one inorganic pigment.

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 / O), or a multiple Emulsions, for example of the water-in-oil-in-water (W / O / W) type Gel, a hydrodispersion, a solid stick or even an aerosol.

The cosmetic preparations according to the invention can be cosmetic Contain auxiliaries, as is customary in such preparations be used, for. B. preservatives, bactericides, antioxidants, Perfumes, antifoaming agents, dyes, pigments, pigments have a coloring effect, thickener, surface-active sub punching, emulsifying, softening, moisturizing and / or moisturizing substances, fats, oils, waxes or other common substances components of a cosmetic formulation such as alcohols, polyols, polymers Foam stabilizers, electrolytes, organic solvents or silicone derivatives.  

If the cosmetic or dermatological preparation is a solution or Lotion can be used as a solvent:

• - water or aqueous solutions;
• - Oils, such as triglycerides of capric or caprylic, preferably but 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 len 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 analogous 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 their derivatives, peptides such as D, L-carnosine, D-carnosine, L-carnosine and their derivatives (eg anserine), carotenoids, caro tine (eg, α-carotene, β-carotene, lycopene) and their derivatives, lipoic acid and their derivatives (eg dihydrolipoic acid), aurothioglucose, propylthiouracil and other thiols (eg thioredoxin, glutathione, cysteine, cystine, cystamine and their glycosyl, N-acetyl, methyl, ethyl, propyl, amyl, butyl and lauryl, Palmitoyl, oleyl, γ-linoleyl, cholesteryl and glyceryl esters) and theirs  Salts, dilauryl thiodipropionate, distearyl thiodipropionate, thiodipropionic acid and their derivatives (esters, ethers, peptides, lipids, nucleotides, nucleosides and Salts) as well as sulfoximine compounds (eg buthionine sulfoximines, homocysts insulfoximine, buthionine sulfone, penta, hexa, heptathionine sulfoximine) in very low tolerated dosages (eg pmol to μmol / kg), furthermore (metal) chelators (eg, α-hydroxy fatty acids, palmitic acid, phytic acid, lactoferrin), α-hydronic acids (eg citric acid, lactic acid, malic acid), humic acid, Bile acid, biliary extracts, bilirubin, biliverdin, EDTA, EGTA and theirs Derivatives, unsaturated fatty acids and their derivatives (for example 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) as well as Konyferylbenzoat benzoin resin, rutinic acid and its derivatives, ferulic acid and its Derivatives, butylhydroxytoluene, butylhydroxyanisole, nordihydroguaiakolic acid, Nordihydroguajaretsäure, Trihydroxybutyrophenon, uric acid and their Derivatives, mannose and its derivatives, zinc and its derivatives (eg ZnO, ZnSO₄) selenium and its derivatives (eg selenium methionine), stilbenes and their derivatives Derivatives (eg stilbene oxide, trans-stilbene oxide) and the 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 is preferably 0.001 to 30 wt .-%, especially preferably 0.05-20 wt .-%, in particular 1-10 wt .-%, based on the Total weight of 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. B. the ge called fats, oils, waxes and other fats, as well as water and a Emulsifier, as is customary for such a type of formulation is used.

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 is.

Solid pins according to the invention contain z. Natural or synthetic Waxes, fatty alcohols or fatty acid esters. To be favoured 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 in principle would be suitable for the present invention, but to the Nevertheless, because of harmful effects on the environment or other accompanying circumstances should be waived, especially fluorocarbons and Chlorofluorocarbons (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 is about oxides of titanium, zinc, iron, zirconium, silicon, manganese, aluminum miniums, cerers and mixtures thereof, as well as modifications in which the Oxides are the active agents. Particularly preferred are Pigments based on 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 function is the hair or the Preparation to dye itself, electrolytes, preparations against fats 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 they are usually used for this. The surface-active substance may be present in a concentration of between 1% and 50% by weight  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. to aq aqueous or aqueous-alcoholic solutions, optionally surface-active Contain substances, preferably non-ionic or cationic upper surface-active substances whose concentration is between 0.1 and 10% by weight, preferably between 0.2 and 5 wt .-%, may be. This cosmetic or dermatological preparation may also be an aerosol with the übli represent the tools used for this purpose.

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 treatment and care The 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 surface-active Substances. Anionic emulsions are preferably of the soap type and contain at least one ethoxylated or per invention polyoxylated organic compound with anionic or non-ionic Character.

Cosmetic and dermatological preparations for treatment and care The hair may be present as gels, in addition to at least one alkylated hydroquinone according to the invention and usually ver solvents used still organic thickeners, eg. B.  Gum arabic, xanthan gum, sodium alginate, cellulose derivatives, preferably methylcellulose, hydroxymethylcellulose, hydroxyethylcellulose, Hydroxypropylcellulose, hydroxypropylmethylcellulose or inorganic ver 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% by weight, preferably between 0.5 and 15% by weight.

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

The following examples are intended to illustrate the embodiments of the present Illustrate inventions.

example 1

Example 2

Example 3

Example 4

Example 5

Example 6

Example 7

Example 8

Example 9

Example 10

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Example 12

Example 13

Example 14

Example 15

Example 16

Example 17

Example 18

Example 19

Example 20

Example 21

Example 22

The obtained by mixing the respective ingredients liquid Phase is in proportion with a propane-butane mixture (2: 7) 39: 61 filled in aerosol container.  

Example 23

Example 24

Example 25

Example 26

Example 27 Production of capsules

Capsules containing the ingredients listed below, are made according to known procedures. These are for the Treatment of the above purposes in dosage amounts of one each Capsule once or several times daily:

Inulin | 0.5 g hydroxyethyl 0.5 g

The numbers in the above examples are wt%.

Claims (6)

1. Use of one or more compounds from the group the carbohydrates or carbohydrate derivatives as antiadhesive agents towards microorganisms. 2. Use of one or more compounds from the group the carbohydrates or carbohydrate derivatives as antiadhesive agents towards microorganisms as a constituent of preparations. 3. preparations containing one or more compounds Compounds from the group of carbohydrates or carbohydrate derivatives with anti-adhesive activity against microorganisms. 4. Use and preparation according to claims 1-3, characterized characterized in that the carbohydrates are sugars, substituted sugars or Sugar residue-containing compounds are. 5. Use and preparation according to claims 1-3, characterized characterized in that the carbohydrates monosaccharides, disaccharides, Oligosaccharides, amino sugars, sugar esters, sugar ethers, sugar ethoxylates, Glycolipids or polysaccharides. 6. Preparations according to claim 2 or 3, characterized in that it is topical preparations.