DE102004031938A1 - Use of star prepolymers with at least four water-soluble polymer arms having terminal reactive groups for producing a bacteriostatic finish on surfaces, e.g. medical equipment, implants or contact lenses - Google Patents

Abstract

Star prepolymers with at least four water-soluble polymer arms having terminal reactive groups are used for producing a bacteriostatic finish on surfaces. An independent claim is also included for producing a bacteriostatic finish on surfaces by coating the surface with an ultrathin hydrogel-forming coating comprising a star prepolymer with at least four water-soluble polymer arms and crosslinking the prepolymer molecules through the ends of the polymer arms.

Description

The The present invention relates to the use of star-shaped polymers with hydrophilic polymer arms that are reactive at their free ends functional group R contribute to the bacteriostatic equipment of Surfaces.

The bacteriostatic and bactericidal finishing of surfaces of particular interest for objects whose Application a germ-free surface requires, for example, medical items such as surgical instruments, Catheters, syringes, cannulas, Respiratory masks and the like, and in particular implants and contact lenses. Usually one reaches a bacteriostatic or bactericidal equipment of surfaces through equipment the surface with low molecular weight active substances (biocides), which is a killing of Bacteria, which settle on the surface, cause or at least prevent their multiplication. The bactericidal / bacteriostatic Effect of so equipped surface Based on the fact that the active ingredients, especially when in contact with Body fluids be delivered to the environment and so those in the area Kill harmful germs or prevent their reproduction. The delivery of the active ingredients to the Environment is also referred to as "leaching." The However, biocidal agents are often not well tolerated by humans and can intolerance reactions how to cause allergies. In addition, the so-equipped surfaces lose due to the permanent release of the drug over time their bactericidal / bacteriostatic Effect. He wishes are therefore surfaces, the permanent bactericidal or bacteriostatic properties have, d. H. Surfaces, on which a colonization with harmful germs, especially with bacteria, permanently does not occur or is effectively prevented. In addition, should This property can be achieved without requiring a "leaching" of the active ingredients the environment occurs.

on several occasions was trying to solve the problem of leaching by immobilization of knownness biocidal substances on surfaces. So describes WO 01/76594 discloses bacteriostatic finishing of surfaces in which the surface having a plurality of immobilized furanones. Immobilization takes place by means of a polymer.

The WO 02/064183 proposes as biocidal equipment immobilized for surfaces cationic proteins, e.g. Protamine, Mellitin, Cecroprin-A or Nisin ago. The surfaces can additionally a weakly crosslinked hydrogel-forming polymer.

From the US 6,264,936 It is known to fix biocidal metal compounds by a polymeric matrix on a surface. The so-equipped surfaces act on microorganisms as a contact poison.

From the US 6,087,415 For example, antimicrobial coatings are known for biomedical articles such as contact lenses made by coupling carboxyl-containing polymers to the OH or NH ₂ groups on the surface of the biomedical article.

The known from the prior art polymer-based bacteriostatic equipment are not satisfactory. This is often the long-term stability of such equipment inadequate and stability under mechanical stress is not given sufficiently. In many cases prevent complicated manufacturing processes for these equipments a broad applicability, especially with objects with irregular shaped Surfaces. There is therefore a need for suitable bacteriostatic equipments of surfaces, the one enough high long-term resistance show a colonization by bacteria and universally applicable are, d. H. a bacteriostatic equipment of different Materials and surfaces allow. Desirably the bacteriostatic equipment should work the other way the objects, their surface bacteriostatically equipped was, did not affect. About that In addition, the process for producing such equipment should advantageously also from aqueous Preparations can be made.

It has been found that this object can be achieved by hydrogel-forming coatings based on interconnected star-shaped prepolymers having on average at least four polymer arms A, which are soluble in water per se, wherein the crosslinking takes place via the ends of the polymer arms A. Due to the star-shaped structure of the prepolymers used, a dense network of hydrophilic polymer chains is obtained which can be swelled by water, ie hydrogel-forming. Man ver suggests that in this way a colonization of the surfaces by bacteria is effectively reduced or even completely suppressed.

The Crosslinking usually takes place by reaction of reactive groups R, which are arranged at the free ends of the water-soluble polymer arms A. are, with each other or with complementary reactive groups R 'under bond formation. The complementary-reactive Groups R 'can do this both at the ends of the water-soluble arms A star-shaped prepolymers are as well as in various different cross-linking substances.

Therefore the present invention relates to the use of star-shaped prepolymers, which on average have at least four polymer arms A, which in themselves soluble in water are and at their free ends a reactive functional group R carry, with it to complementary groups R 'or with itself react under binding formation, to bacteriostatic equipment of Surfaces.

The The present invention also relates to a method for bacteriostatic equipment of surfaces, which is characterized in that one is a hydrogel-forming Coating consisting of interconnected star-shaped prepolymers are constructed, which have on average at least four polymer arms A, the for seen to be soluble in water are applied to the surface to be coated, wherein the crosslinking of the stellate Prepolymers over the Ends of the polymer arms A takes place.

Under a hydrogel-forming coating is understood by those skilled in the art Coatings that are swollen by water as a result of Intercalation of water molecules in the coating.

Star-shaped polymers are understood as meaning those polymers which have a plurality of polymer chains bonded to a low molecular weight central unit, the low molecular weight central unit generally having from 4 to 100 framework atoms, such as C atoms, N atoms or O atoms. Accordingly, the star-shaped polymers used according to the invention can be described by the following general formula I: Z (ABR) _n (I) wherein
n is an integer having a value of at least 4, e.g. 4 to 12, especially 5 to 12 and especially 6 to 8;
Z is a low molecular weight n-valent organic radical as the central unit, which generally has 4 to 100, preferably 5 to 50, skeletal atoms, in particular 6 to 30 skeletal atoms. The central unit can have both aliphatic and aromatic groups. It is for example one of an at least 4-valent alcohol, for. B. a 4- to 12-valent, preferably an at least 5-valent, especially a 6- to 8-valent alcohol, for. Pentaerythritol, dipentaerythritol, a sugar alcohol such as erythritol, xylitol, mannitol, sorbitol, maltitol, isomaltulose, isomaltitol, trehalulose, or the like;
A is a hydrophilic polymer chain which is water-soluble as such;
B is a chemical bond or a divalent, low molecular weight organic radical having preferably 1 to 20, in particular 2 to 10, carbon atoms, for example a C ₂ -C ₁₀ -alkylene group, a phenylene or a naphthylene group or a C ₅ -C ₁₀ -cycloalkylene group wherein the phenylene, naphthylene and the cycloalkylene group additionally one or more, for. B. 1, 2, 3, 4, 5, or 6 substituents, for. B. alkyl groups having 1 to 4 carbon atoms, alkoxy groups having 1 to 4 carbon atoms or halogen; and
R is a reactive group which can react with a complementary reactive functional groups R 'or with itself under bond formation.

reactive Groups R in this sense are those with nucleophiles in one Addition or substitution reaction react, for. B. isocyanate groups, (Meth) acrylic groups, oxirane groups, oxazoline groups, carboxylic acid groups, carboxylate and carboxylic anhydride groups, carboxylic acid and sulfonic acid halide groups, but also the complementary, nucleophile-reactive groups such as alcoholic OH groups, primary and secondary Amino groups, thiol groups and the like. As an example of carboxylic acid ester groups are in particular so-called active ester groups of the formula -C (O) O-X preferably, wherein X is for Pentafluorophenyl, pyrrolidine-2,5-dione-1-yl, benzo-1,2,3-triazol-1-yl or a carboxamidine residue.

Also suitable as reactive groups R are free-radically polymerizable C =C double bonds, eg. B. in addition to the abovementioned (meth) acrylic groups, vinyl ether and vinyl ester groups, furthermore activated C =C double bonds, activated C =C triple bond and N =N double bonds, with allyl groups in the sense of an ene reaction or with conjugated diolefin groups react in the sense of a Diels-Alder reaction. Examples of groups which can react with allyl groups in the sense of an ene reaction or with dienes in the sense of a Diels-Alder reaction are maleic acid and fumaric acid groups, maleic acid ester and fumaric acid ester groups, cinnamic acid ester groups, propiolic acid (ester) groups, Maleic acid amide and fumaric acid amide groups, maleimide groups, azodicarboxylic ester groups and 1,3,4-triazoline-2,5-dione groups.

In a preferred embodiment has the star-shaped prepolymer those functional groups that undergo an addition or substitution reaction accessible by nucleophiles are. Which includes also groups that react in the sense of a Michael reaction. Examples are in particular isocyanate groups, (meth) acrylic groups (react in the sense of a Michael reaction), oxirane groups or carboxylic acid ester groups. A particularly preferred embodiment concerns star-shaped prepolymers having as reactive groups R isocyanate groups.

In another embodiment indicates the prepolymer ethylenically unsaturated, radically polymerizable double bonds as reactive groups R up.

According to the invention the star-shaped prepolymers on average at least 4, preferably at least 5 and in particular at least 6 polymer arms, often but not more than 16, especially not more than 12 and especially not more than 10 polymer arms. Particularly preferred are the Star shaped prepolymers 6 to 8 polymer arms A on. The number average molecular weight of Polymer arms are typically in the range of 200 to 20,000 daltons, preferably in the range of 300 to 15,000 daltons, in particular in Range from 500 to 10,000 daltons and especially in the range of 1000 up to 8,000 daltons.

Accordingly has the star-shaped prepolymer a number average molecular weight in the range of usually at least 1500 daltons, preferably 2000 to 100,000 daltons, in particular 3000 to 80,000 daltons and specifically 6000 to 60,000 daltons.

The Determination of the molecular weight of the star-shaped polymers can in in known manner by gel permeation chromatography, taking on commercial Columns, Detectors and evaluation software can fall back. At known Number of end groups per polymer molecule can be the molecular weight also determine by titration of the end groups R, in the case of isocyanate groups z. B. by reaction with a defined amount of a secondary amine such as dibutylamine and subsequent titration of the excess amine with acid.

The sufficient swellability of the coating by water is through the water solubility the polymer arms A guaranteed. Sufficient swellability of the coating by water is usually then ensures if the molecular structure, d. H. at least the type of repeat units, preferably also the molecular weight of the polymer arm, a polymer corresponds to its solubility in water at least 1% by weight and preferably at least 5% by weight (at 25 ° C and 1 bar).

Examples of such polymers with sufficient water solubility are poly-C ₂ -C ₄ -alkylene oxides, polyoxazolines, polyvinyl alcohols, homopolymers and copolymers which contain at least 50 wt .-% of N-vinylpyrrolidone in copolymerized form, homopolymers and copolymers containing at least 30 wt. % Hydroxyethyl (meth) acrylate, hydroxypropyl (meth) acrylate, acrylamide, methacrylamide, acrylic acid and / or methacrylic acid in copolymerized form, hydroxylated polydienes and the like.

In a preferred embodiment, the polymer arms A are derived from poly-C ₂ -C ₄ -alkylene oxides and are in particular selected from polyethylene oxide, polypropylene oxide and polyethylene oxide / polypropylene oxide copolymers, which may have a block or a random arrangement of the repeat units. Particular preference is given to star-shaped prepolymers whose polymer arms A are derived from polyethylene oxides or from polyethylene oxide / polypropylene oxide copolymers having a propylene oxide content of not more than 50%.

The inventively used for the prepolymers are z. T. known, for. From WO 98/20060, US 6,162,862 (Polyether star polymers), Chujo Y. et al., Polym. J. 1992, 24 (11), 1301-1306 (star-shaped polyoxazolines), WO 01/55360 (star-shaped polyvinyl alcohols, star-shaped vinylpyrrolidone-containing copolymers) or can be prepared by the methods described therein.

The star-shaped prepolymers used in accordance with the invention are generally prepared by functionalizing suitable star-shaped prepolymer precursors which already have the above-described prepolymer structure, ie at least 4 water-soluble polymer arms and which each have a functional group R "at the ends of the polymer arms , which can be converted into one of the aforementioned reactive groups R. The groups R "include aliphatic or aromatic C atoms, preferably halogen atoms bound to a primary aliphatic carbon atom, in particular chlorine, bromine or iodine, an aliphatic or aromatic and in particular a primary, aliphatic carbon atom bonded OH groups, thiol groups and NHR ² groups with R ² = hydrogen or C ₁ -C ₄ alkyl.

Such prepolymer precursors are known in the art, e.g. B. from the US 3,865,806 . US 5,872,086 . US 6,162,862 , Polym. J. 1992, 24 (11), 1301-1306, WO 01/55360 and commercially available, e.g. B. in the case of star-shaped poly-C ₂ -C ₄ alkylene oxides under the trade designations VORANOL ^®, Terralox ^{®, ®} and SYNALOX DOWFAX ^® of Dow Chemical Corporation, Sorbeth ^® from Glyco Chemicals Inc. and GLUCAM ^® Amerchol Corp. or may be prepared by known methods of polymer chemistry by polymerization of suitable monomers in the presence of polyfunctional initiators, e.g. By "living" polymerization (see: Hsieh, HL; Quirk, RP Anionic polymerization: Principles and Practical Applications, New York, Marcel Dekker, 1996. Matyjaszewski, K. Controlled / Living radical polymerization: Progress in ATRP, NMP, and RAFT, Washington, DC: American Chemical Society, 2000) or, more particularly, in the case of ethylenically unsaturated monomers by atom transfer radical polymerization (ATRP) according to the methods described in WO 98/40415.

The Functionalization of the star-shaped Prepolymer precursors can basically in analogy to known functionalization processes of the prior art the technique done.

For the preparation of prepolymers which carry amino groups on the ends of the polymer arms A, suitable starting materials are in particular those prepolymer precursors which have OH groups at the ends of the polymer arms. The conversion of OH groups into amino groups can, for. In analogy to that of Skarzewski, J. et al. Monatsh. Chem. 1983, 114, 1071-1077. To this end, the OH groups in a conventional manner (such. As to Organikum, 15th ed., VEB, Berlin 1981 S. 241ff .; J. March, Advanced Organic Synthesis ^3rd ed. P 382 ff) with a halogenating agent such as thionyl chloride, sulfuryl chloride, thionyl bromide, phosphorus tribromide, phosphorus oxychloride, oxalyl chloride and the like, optionally in the presence of an auxiliary base such as pyridine or triethylamine, into the corresponding halide, or with methanesulfonyl chloride in the corresponding mesylate. The halogen compound or mesylate thus obtained is then converted into the corresponding azide with an alkali metal azide, preferably in an aprotic polar solvent such as dimethyl sulfoxide, dimethylformamide, dimethylacetamide or N-methylpyrrolidone. The azide is then converted into the amino compound with hydrogen in the presence of a transition metal catalyst or with a complex hydride such as lithium aluminum hydride.

The Production of prepolymers, which carry oxirane groups at the ends of the polymer arms, succeed for example, by reacting prepolymer precursors attached to the ends of the polymer arms A have OH groups, with glycidyl chloride.

The preparation of prepolymers which carry (meth) acrylic groups at the ends of the polymer arms, for example, by esterification of prepolymer precursors which carry OH groups at the ends of the polymer arms A, with acrylic acid or methacrylic acid or by reaction of the OH Groups with acrylic chloride or with methacryl chloride in analogy to known methods. Alternatively, in prepolymer precursors which carry NH ₂ groups at the ends of the polymer arms, the NH ₂ groups can be reacted with acrylic acid or methacrylic acid or with their acid chlorides. The preparation of (meth) acrylate-terminated prepolymers may, for. For example, in analogy to the Cruise et al. Biomaterials_1998, 19, 1287-1294 and Han et al. Macromolecules 1997, 30, 6077-6083 for the modification of polyether diols and triols described methods.

The Production of prepolymers, which carry thiol groups at the ends of the polymer arms A succeed for example, by reacting prepolymer precursors attached to the ends of the polymer arms A carry halogen atoms, with thioacetic acid and subsequent hydrolysis in analogy to that in Houben-Weyl, Methods of Organic Chemistry, Ed. E. Müller, 4th ed., Vol. 9, p. 749, G. Thieme, Stuttgart 1955 described Method.

The preparation of prepolymers which carry isocyanate at the ends of the polymer arms, succeeds preferably by addition of a low molecular weight diisocyanate to prepolymer precursors which have OH-SH- or NHR "groups at the ends of the polymer arms A (R '= H, or an aliphatic radical). Preferably star-shaped polyols are used with OH end groups.

When Diisocyanates come both aromatic diisocyanates such as toluene-2,4-diisocyanate, toluene-2,6-diisocyanate, commercially available Mixture of toluene-2,4- and 2,6-diisocyanate (TDI), m-phenylene diisocyanate, 3,3'-diphenyl-4,4'-biphenylene diisocyanate, 4,4'-biphenylene diisocyanate, 4,4'-diphenylmethane diisocyanate, 3,3'-dichloro-4,4'-biphenylene diisocyanate, Cumene-2,4-diisocyanate, 1,5-naphthalene diisocyanate, p-xylylene diisocyanate, p-phenylene diisocyanate, 4-methoxy-1,3-phenylene diisocyanate, 4-chloro-1,3-phenylene diisocyanate, 4-bromo-1,3-phenylene diisocyanate, 4-ethoxy-1,3-phenylene, 2,4-dimethyl-1,3-phenylene diisocyanate, 5,6-dimethyl-1,3-phenylene diisocyanate, 2,4-diisocyanatodiphenyl ether, benzidine diisocyanate, 4,6-dimethyl-1,3-phenylene diisocyanate, 9,10-anthracene diisocyanate, 4,4'-diisocyanatodibenzyl, 3,3'-dimethyl-4,4'-diisocyanatodiphenylmethanes, 2,6-dimethyl-4,4'-diisocyantodiphenyl, 2,4-diisocyanatostilbene, 3,3'-dimethoxy-4,4'-diisocyanate diphenyl, 1,4-anthracene diisocyanate, 2,5-fluorene diisocyanate, 1,8-naphthalene diisocyanate, 2,6-diisocyanatobenzofuran, as well as aliphatic and cycloaliphatic diisocyanates such as isophorone diisocyanate (IPDI), ethylene diisocyanate, ethylidene diisocyanate, propylene-1,2-diisocyanate, Cyclohexylene-1,2-diisocyanate, Cyclohexylene-1,4-diisocyanate, 1,6-hexamethylene diisocyanate, 1,4-tetramethylene diisocyanate, 1,10-decamethylene diisocyanate and methylenedicyclohexyl diisocyanate.

Prefers are diisocyanates whose isocyanate groups differ in their reactivity, such as toluene-2,4-diisocyanate, toluene-2,6-diisocyanate, as well as mixture toluene-2,4- and 2,6-diisocyanate and cis and trans isophorone diisocyanate.

Especially preferred are star-shaped prepolymers with aliphatic diisocyanate end groups, in particular those such by addition of IPDI to the chain ends of OH group-terminated stellate Präpolymervorstufen to be obtained.

The star polymers are naturally reacted with the diisocyanate such that a diisocyanate unit is added to each chain end of the star molecules, leaving the second isocyanate group of the diisocyanate free. In this way, each end group of the star molecules is provided with a free isocyanate group via a urethane linkage. Methods for this are, for example, from US 5,808,131, WO 98/20060 and US 6,162,862 , Bartelink CF et al., J. Polymer Science 2000, 38, 2555-2565 and Götz et al., Macromolecular Materials and Engineering 2002, 287, pp. 223-230.

In Typically, for this purpose, the prepolymer precursor will be avoided the formation of multimeric adducts, d. H. Adducts in which two or more prepolymers via diisocyanate units linked together are, in a surplus of the diisocyanate. As a rule, the excess is at least 10 mol%, based on the stoichiometry the reaction, d. H. it is at least 1.1 mol, preferably at least 2 moles and especially at least 5 moles of diisocyanate and especially at least 10 moles of diisocyanate per mole of functional group in the prepolymer precursor one. Preferably, the reaction is carried out under controlled reaction conditions, d. H. the addition of the prepolymer precursor takes place under reaction conditions so slowly that a heating of the Reactor content is avoided by more than 20 K. Preferably takes place the implementation of the prepolymer precursor with the diisocyanate in the absence of a solvent or diluent.

The Reaction can be more usual in the absence or presence of small amounts Catalysts that promote the formation of urethanes occur. Suitable catalysts are, for example, tertiary amines such as Diazabicyclooctane (DABCO) and organotin compounds, e.g. B. Dialkyltin (IV) salts of aliphatic carboxylic acids such as dibutyltin dilaurate and dibutyltin dioctoate. The amount of catalyst is usually not more than 0.5% by weight, based on the prepolymer precursor, e.g. B. 0.01 to 0.5 wt .-%, in particular 0.02 to 0.3 wt .-%. In a preferred procedure no catalyst is used.

The naturally required reaction temperatures depend on the Reactivity the prepolymer precursor used, of the diisocyanate and, if used, the type and amount of used catalyst. It is usually in the range of 20 to 100 ° C and in particular in the range of 35 to 80 ° C. It goes without saying that the implementation of the prepolymer precursor with the diisocyanate in the absence of moisture (<2000 ppm, preferably <500 ppm).

The work-up of the reaction mixture thus obtained is generally carried out by distilling off the excess diisocyanate, preferably at reduced pressure. The resulting reaction products ent For the most part, the star-shaped prepolymer has isocyanate groups at the ends of the polymer arms. The proportion of the star-shaped prepolymer is generally at least 70 wt .-%, preferably at least 80 wt .-% of the reaction product. The remaining constituents of the reaction product are essentially dimers and in minor proportions trimers which are likewise suitable in these amounts for the preparation of the coatings according to the invention.

The surfaces to be finished according to the invention are fundamentally subject to no restrictions. The surfaces may be regular or irregularly shaped, smooth or porous. Examples of suitable surface materials are oxidic surfaces, e.g. Silicates such as glass, quartz, silica as in silica gels, or ceramics, furthermore semimetals such as silicon, semiconductor materials, metals and metal alloys such as steel, polymers such as polyvinyl chloride, polyethylene, polymethylpentenes, polypropylene, polyesters, fluoropolymers (eg ^Teflon® ) , Polyamides, polyurethanes, poly (meth) acrylates, blends and composites of the aforementioned materials. Suitable surfaces are also fiber materials, for example natural fibers such as cellulose fibers, silk, cotton fibers and wool, as well as synthetic fibers such as PE and PP fibers, polyester fibers, polyamide fibers, acrylic fibers and the like. The fibers may be in the form of yarns, fabrics, knits and nonwovens.

The bacteriostatic equipment is usually done by depositing the star-shaped prepolymers on the equipped surface and subsequent Crosslinking of the reactive groups R of the prepolymers. The steps of Deposition and networking can if desired be carried out repeatedly. You get in this way to thicker layers.

• i. Aufbringen einer Lösung wenigstens eines sternförmigen Präpolymers, das im Mittel wenigstens vier Polymerarme A aufweist, die für sich gesehen in Wasser löslich sind und an ihren freien Enden eine reaktive funktionelle Gruppe R tragen, auf die zu beschichtende Oberfläche und
• ii. anschließend Durchführen einer Verknüpfungsreaktion der reaktiven Gruppen untereinander.

Typically, this procedure involves the following steps:

• i. Applying a solution of at least one star-shaped prepolymer having on average at least four polymer arms A, which in themselves are soluble in water and carry at their free ends a reactive functional group R, on the surface to be coated and
• ii. then performing a linking reaction of the reactive groups with each other.

The Crosslinking usually takes place by reaction of reactive groups R, which are arranged at the free ends of the water-soluble polymer arms A. are, with each other or with complementary reactive groups R 'under bond formation. The complementary-reactive Groups R 'can do this both at the ends of the water-soluble arms A star-shaped prepolymers are as well as in various different cross-linking substances.

By the inventive method be on the surface Hydrogelbildendende coatings obtained from each other linked, stellate prepolymers are built and dependent of the manufacturing process on its surface originally in the prepolymer contained reactive groups R can have. The coatings can on their surface also have such reactive groups R, as a result of the crosslinking reaction have arisen.

Examples for deposition processes are the immersion of the surface to be coated in the solution of the prepolymers as well as the spincoating - here becomes the solution of the prepolymer applied to the rotating at high speed surface to be coated. It goes without saying that you can make ultra-thin coatings the coating measures usually carried out under dust-free conditions.

at the immersion process immersed the substrates in a solution of Star polymer in a suitable solvent and then drain the solution, making a thinner liquid film with as possible uniform thickness remains on the substrate. This is then dried. The resulting film thickness depends from the concentration of the star polymer solution. Subsequently, will the networking triggered.

At the Spincoating usually becomes the initially non-rotating substrate with the solution of the star-shaped prepolymers Completely wetted. Subsequently is the substrate to be coated with high numbers of revolutions, in usually at least 50 rpm, often at least 500 rpm, e.g. 500 to 30,000 rpm, preferably above 1000 rpm, z. From 1000 to 10,000 rpm, and more preferably 3000 to 6000 rev / min, set in rotation, the solution largely is thrown off and a thinner Coating film on the surface of the substrate remains. Then, here is a networking triggered.

Usually, the concentration is at least 0.001 mg / ml, preferably at least 0.1, in especially at least 1 mg / ml, more preferably at least 0.1 mg / ml, most preferably at least 10 mg / ml. The concentration of the prepolymer in the solution will usually not exceed a value of 500 mg / ml, preferably 250 mg / ml and especially 100 mg / ml. Naturally, the concentration of the coating can be controlled via the concentration.

In order to achieve the desired bacteriostatic properties, the hydrogel coating will generally have a layer thickness of at least 2 nm, preferably at least 5 nm and in particular at least 10 nm (measured by ellipsometry according to the method described in Guide to using WVASE 32 ^TH , JA Woollam Co. Ind. Lincoln NE USA 1998 described method). As a rule, one will not exceed coating thicknesses of 1 .mu.m, in particular 500 nm and especially 200 nm in order not to impair the function of the articles which comprise the bacteriostatic composition according to the invention. Of course, the bacteriostatic effect of such hydrogel coatings is not lost at greater layer thicknesses, so that bacteriostatic equipment according to the invention can have layer thicknesses of, for example, up to 200 μm or up to 150 μm.

to Production of the solutions the prepolymer are basically all solvents suitable, which no or only a low reactivity with respect to functional groups R of the prepolymer exhibit. Among them, those having a high vapor pressure are preferable have and thus can be easily removed. Preferred are therefore such solvents at normal pressure, a boiling temperature below 150 ° C and preferably below 120 ° C exhibit. examples for suitable solvents are aprotic solvents, z. As ethers such as tetrahydrofuran (THF), dioxane, diethyl ether, tert-butyl methyl ether, aromatic hydrocarbons such as xylenes and toluene, further Acetonitrile, propionitrile and mixtures of these solvents. In the case of prepolymers with OH, SH, carboxyl, (meth) acrylic and oxirane groups are also protic solvents such as water or alcohols, eg. Methanol, ethanol, n-propanol, isopropanol, n-butanol and tert-butanol, as well as their mixtures with aprotic solvents suitable. In the case of prepolymers with isocyanate groups are surprisingly also in addition to the aforementioned aprotic solvents Water and mixtures of water with aprotic solvents suitable, since probably the degradation of the isocyanate groups in the prepolymers comparatively slowly.

The type of networking can be done in different ways. For example, the article coated with the uncrosslinked prepolymer may be treated with a crosslinking agent. As crosslinking agents, in principle all polyfunctional compounds are suitable whose functional groups react with the functional groups of the prepolymer to form bonds. These functional groups are also referred to below as complementary functional groups R '. An overview of complementary functional groups R 'is given in Table 1, wherein the reactive groups R of the prepolymer are indicated in the first row and the groups R' complementary thereto in the first column: Table 1: Complementary functional groups

Therefore takes place according to a first embodiment The invention provides the provision of bacteriostatic equipment a process that involves linking the reactive groups R by addition of a compound V1, the at least two reactive Having groups R 'per molecule, those with the reactive groups R of the star-shaped prepolymer under bond formation responding.

at the polyfunctional compounds V1 may be low molecular weight Act connections, z. B. to aliphatic or cycloaliphatic Diols, triols and tetraols, e.g. As ethylene glycol, butanediol, diethylene glycol, Triethylene glycol, trimethylolpropane, pentaerythritol and the like, aliphatic or cycloaliphatic diamines, triamines or tetramines, z. Ethylenediamine, diethylenetriamine, triethylenetetramine, tetraethylenepentamine, 1,8-Diamino-3,6-dioxaoctane Diaminocyclohexane, isophoronediamine and the like, aminoalcohols such as Ethanolamine, diethanolamine, aliphatic or cycloaliphatic Dithiols to dicarboxylic acids or tricarboxylic acids like sebacic acid, glutaric, adipic acid, phthalic acid, isophthalic acid, or the aforementioned diisocyanates, depending on which type of reactive groups the prepolymer having. The low molecular weight polyfunctional compounds have unlike the prepolymers usually a molecular weight <500 g / mol.

The Polyfunctional compound V1 can already be found in the solution of prepolymers be included, which is used for coating. In the first resulting Coating of largely uncrosslinked prepolymers then react, for. B. when drying or heating the coating, the reactive groups R 'of the crosslinking agent with the reactive Groups R of the prepolymer and thus form a layer of interconnected ones Prepolymers.

If the reactive groups R of the prepolymer are conjugated dienes Accordingly, the connection V1 becomes at least two have dienophilic groups and vice versa. When the prepolymers have reactive groups that undergo an ene reaction is the compound V1 have at least two allylic double bonds. In general, such systems are used to produce the Coatings solutions use both the prepolymer and the compounds V1 included. The networking then takes place when drying the primary obtained coating, optionally after heating.

When Polyfunctional compounds V1 are in principle also prepolymers suitable, which have at least four polymer arms A, which in itself soluble in water are and at their free ends a reactive functional group R ', the with the reactive groups R of the prepolymer under bond formation react. In other words, to provide the bacteriostatic equipment can According to the invention also solutions of at least two different prepolymers are used, wherein the one prepolymer reactive groups R and the other complementary reactive Groups R 'has. Also In this way, a layer of cross-linked prepolymers receive.

In another embodiment The invention is the link the reactive groups R are triggered, by adding a sufficient amount of a compound V2, the with a portion of the reactive groups R to form reactive groups R 'reacts, which reacts with the remaining reactive groups R to form bonds. In the case of prepolymers With isocyanate groups, for example, the crosslinking can be initiated by one treats the coated article with water, for. B. by Store in a humid atmosphere or under water. Here, a part of the isocyanate groups reacts to form amino groups, which in turn with the remaining Isocyanate groups react to form bonds, with a layer from cross-linked prepolymers arises. The crosslinking agent V2 is thus here water.

In a variant of this embodiment you put solutions of the prepolymer in water or in a mixture of water with one or more water-miscible solvents one. examples for suitable, water-miscible solvents are in particular those which are not or only very much slower with the isocyanate groups as water enter into a reaction. Examples are cyclic ones Ethers such as tetrahydrofuran and dioxane, furthermore N-alkylamides such as N-methylpyrrolidone, Dimethylformamide and dimethylacetamide. The mixing ratio of water: solvent is usually in the range of 1: 100 to 1: 100, preferably in the range of 50: 1 to 1:10 and especially in the range 20: 1 to 1: 1. This variant is particularly suitable for producing thicker Layers. The concentration of prepolymer is then preferably in the range of 1 to 500 mg / ml, especially in the range of 5 to 200 mg / ml and especially in the range of 10 to 100 mg / ml.

In a further embodiment of the invention, the group R is selected from ethylenically unsaturated, radically polymerizable double bonds. The networking takes place in this case, in a thermal or photochemical manner, d. H. by Irradiation with UV radiation or with electron radiation. In the event of the photochemical crosslinking by UV radiation is the solution of the prepolymers usually add suitable photoinitiators. The type and quantity on photoinitiator, which triggers a photochemical crosslinking is required, is the expert radiation-hardening technology Paints common.

In a further embodiment of the invention, a solution of a star-shaped prepolymer, for example as a monolayer, is first applied to the surface to be coated, if desired, and partial crosslinking of the reactive groups R is carried out, followed by at least one further star-shaped prepolymer 2 so treated surface having at least four polymer arms A, which are individually soluble in water and having at their free ends a reactive functional group R ', which have a complementary to the reactive groups R of the first prepolymer reactivity. If appropriate, a subsequent crosslinking of the remaining reactive groups R 'is then carried out. This process can be repeated one or more times. In this way, it is possible to selectively produce multilayer coatings. This procedure is also referred to below as layer-by-layer method. The layer-by-layer method can be realized in a particularly elegant manner with prepolymers which have reactive groups R which react with compounds R 2 to form reactive groups R 'which have a reactivity which is complementary to the groups R. Examples of R groups are isocyanate groups. The compound V2 is water in this case. As complementary reactive groups R 'then arise NH ₂ groups. If, in fact, the crosslinking of the first layer with the compound V2 is triggered, the resulting coating has on its surface free groups R '(for example amino groups). These then react with the groups R (for example isocyanate groups) of the prepolymers applied in a second coating process to form bonds.

In addition to the crosslinked star-shaped prepolymers, the hydrogel-forming coatings can be water-soluble polysaccharides, such as hyaluronates, heparins, alginates or z. B. dextrans. The preparation of such coatings is accomplished by co-depositing prepolymer and water-soluble polysaccharide on the surface to be finished. When using prepolymers with opposite OH functions reactive functional groups R, z. As isocyanate groups, then the polysaccharide acts as a crosslinker. Polysaccharide and prepolymer then together form the hydrogel-forming coating. The weight ratio of polysaccharide to star-shaped prepolymer in the coating will usually not exceed a value of 1: 1 and is for example in the range of 1: 1000 to 1: 1 and especially in the range of 1: 100 to 1: 2.

The bacteriostatic effect of the surfaces according to the invention can be increased by additionally incorporating into the coating built up from the crosslinked prepolymers components which are known to act as biocides and / or bactericides. These include in particular antibiotics such as streptomycin, gentomycin, penicillin, neomycin, acriflavine, ampicillin, Cu salts, silver salts, zinc salts, wherein the salts may be present in the layer in a homogeneous distribution or as finely divided particles, for. In the form of colloidal metal oxides such as, for example, colloidal zinc oxide as described in U.S. Pat DE 101 63 256 compounds of bisguanidines, quaternary pyridinium salt compounds, compounds of phosphonium salts, isothiazolones, thiazoylbenzimidazoles, sulfonyl compounds, salicylic compounds, furthermore peptides with known biocidal activity, for example maiganin-type peptides, anopline, nisin, chitosan, defensin, sapecin, royalisin, tenecin, Cecropins and the like. The incorporation of these biocidal foreign substances can be carried out in the manner described above. The weight ratio of biocidal / bactericidal foreign substances to prepolymer (calculated as starting material) will generally not exceed a value of 1: 1 in order not to impair the properties of the hydrogel coating according to the invention. If a biocidal / bactericidal foreign constituent is to be incorporated, the weight ratio of biocidal / bactericidal foreign constituent to prepolymer is generally at least 1: 1000 and in particular at least 1: 100.

Of the Incorporation of the biocidal / bactericidal agents used to increase the effect Substances in the equipment according to the invention takes place preferably by coadsorption from solutions containing the prepolymer and the biocidal / bactericidal substance. In addition, the prepolymers with the said biocidal / bactericidal substances before adsorption be reacted or as a mixture with unmodified prepolymers on the surface the coating are reacted. Of course it is it also possible targeted by physisorption or chemisorption on the finished Apply hydrogel coating. Biocidal / bactericidal substances be incorporated in particular by the inventive equipment that one she in the solution the prepolymer suspended or dissolved. In the subsequently triggered networking these substances are incorporated into the coating in a manner that they are not or only to a very limited extent released to the environment become. An otherwise usual Leaching is not observed.

Next The biocidal / bactericidal impurities may also contain other foreign materials, that is, materials that do not form hydrogel-forming coatings, incorporated into the inventive equipment become. Which includes bioactive materials such as medicines, eg .. antineoplastic agents, Local anesthetics, hormones, antiangiogenic agents, neurotransmitters, furthermore oligonucleotides, DNA, RNA, natural and synthetic peptides, natural and synthetic proteins, growth factors such as BMPs (bone morphogenic proteins), HGHs (human growth hormone), GMCSF (Macrophage colony stimulating factors), heparin-binding factors such as FGFs, VGF, TGFs, communication and architecture-conveying signaling materials such as BHL, HHL, OHL, DHL, OHHL, OHL, ODHL, OdDHL, HBHL, HtDHL and others, Integrin-mediating signaling molecules, proteins such as fibronectin, Laminin, vitronectin, collagen, thrombospondin and other adhesion promoting agents Proteins, mechanically or otherwise physically modulated proteins such as stretched fibronectin, cyclodextrins, lipids, synthetic polymers, for example perfluorinated polymers, homo and copolymers of maleic anhydride, inorganic components, e.g. Apatites and hydroxyapatides, metals in particulate form, in particular in the form of nanoparticles, quaternary ammonium salt compounds or organometallic compounds, markers z. B. organic dyes and fluorescent dyes and radioactive substances.

The weight ratio from foreign constituent to prepolymer (calculated as starting material) is usually a value of 1: 1 do not exceed. If an external component is to be installed, the weight ratio of Foreign constituent to prepolymer usually at least 1: 1000 and in particular at least 1: 100.

Frequently it is advantageous to equip the surface pretreat in a way that they have an increased number (area density) having functional groups R ', those with the functional groups R of the prepolymer under bond formation can react.

For this purpose, the surfaces of inert materials are often chemically before the actual equipment activate. This can be done for example by treatment of the surface to be coated with acid or alkali, by oxidation (flaming), by electron beam irradiation or by a plasma treatment with an oxygen-containing plasma as described by P. Chevallier et al. J. Phys. Chem. B 2001, 105 (50), 12490-12497; in JP 09302118 A2 ; in DE 10011275 ; or by D. Klee. et al. Adv. Polym. Sci. 1999, 149, 1-57. The activation of the surface can also be carried out by means of plasma treatment with an NH ₃ -containing plasma, as described in US Pat US 6,017,577 , 6,040,058 and 6,080,488.

you can be equipped surface also treat with compounds that are known to have good adhesion to the surface and that also have functional groups R ', which are complementary to the functional groups R of the star-shaped prepolymer. Suitable groups R 'are, dependent from the reactive group R of the prepolymer: isocyanate, amino, Hydroxyl and epoxy groups, furthermore groups which in the sense of a Michael addition dienophilic groups, the Diels-Alder addition reactions undergo electron-deficient double bonds in a Diels-Alder Addition or ene reaction react with allylic double bonds; activated ester groups; oxazoline; as well as vinyl groups and thiols, which specifically enter into a free radical addition.

The Nature of the group that causes adhesion to the surface, of course, depends on the chemical nature of this surface from. In the case of oxidic, such as ceramic and glassy surfaces, as well in the case of metallic surfaces have connections proven, the adhesion-promoting groups silane groups, in particular Having trialkoxysilane groups. Examples of such compounds are trialkoxyaminoalkylsilanes such as triethoxyaminopropylsilane and N [(3-triethoxysilyl) propyl] ethylenediamine, Trialkoxyalkyl-3-glycidyl ether silanes such as triethoxypropyl-3-glycidyl ether silane, Trialkoxyalkylmercaptans such as triethoxypropylmercaptan, trialkoxyallylsilanes such as allyltrimethoxysilane and trialkoxysilylacryloxyalkanes and -acrylamidoalkanes such as 1-triethoxysilyl-3-acryloxypropane. For oxidic Materials and plastic materials are considered adhesion-promoting Groups also suitable polyfunctional polyammonium groups. Examples for such compounds are polyammonium compound with free primary amine groups as z. By J. Scheerder, J.F.J Engbersen, and D.N. Reinhoudt, Recl. Trav. Chim. Pays-Bas 1996, 115 (6), 307-320, and Decher, Science 1997, 277, 1232-1237 for this purpose.

Prefers the aforementioned compounds are applied as a monolayer on the surface to be finished. Such monolayers can be carried out in a manner known per se Treat the surfaces to be coated with dilute solutions of Reach connections, z. B. after the immersion method described above or by spincoating. solvent and concentrations correspond to those for the application of the prepolymers information provided. Often It is recommended that the surfaces treat with the aforementioned compounds known to be a good adhesion to the surface have, after activation by flaming, through Electron irradiation or by plasma treatment.

The Draw surfaces equipped according to the invention characterized by a bacteriostatic effect against both gram-positive as well over gram-negative bacteria. Examples of bacteria against which the coatings comprise bacteriostatic properties Bacillus anthracis, Bacillus cereus, Bacteroides sp., Bordetella pertussis, Campylobacter sp., Chlamydia pneumoniae, Chlamydia trachomatis, Clostridium botulinum, Clostridium difficile, Clostridium perfringens, Clostridium tetani, Corynebacterium diphtheriae., Corynebacterium sp., Enterococcus spp. (formerly Streptococcus), Escherichia coli, Haemophilus influenzae, Helicobacter pylori, Klebsiella sp., Legionella pneumophila, Listeria monocytogenes, Moraxella catarrhalis, Mycobacterium leprae, Mycobacterium tuberculosis, other Mycobacterium sp., Mycoplasma pneumoniae, Neisseria gonorrhoeae, Neisseria meningitidis, Proteus sp., Pseudomonas aeruginosa, other Pseudomonas sp., Salmonella typhi / paratyphi, other Salmonella sp., Shigella sp., Staphylococcus aureus, Staphylococcus epidermidis, Streptococcus agalactiae (group B -hememolytic), Streptococcus pneumoniae, Streptococcus pyogenes (group A -hememolytic), Streptococcus viridans and Vibrio cholerae. The equipment according to the invention acts especially bacteriostatic to Pseudomona aeruginosa, Staphylococcus Aureus, Escherichia coli, Dermacoccus and Bradyrhizobium. The coatings are biocompatible due to their chemical composition and not toxic.

The Inventive equipment records characterized by high long-term stability, even when in contact with liquids, for example, body fluids out. She is also stable towards Influence of mechanical forces.

The method according to the invention is particularly suitable for the bacteriostatic treatment of the surfaces of objects which are in direct contact with living matter, in particular with Körperge tissue such as subcutaneous and intramuscular tissues, with internal or external surfaces of organs (especially heart, kidney, lung) or blood vessels such as temporary and permanent implants, endoscopes, surgical instruments, catheters, and the like. The coatings can be applied on many laboratory utensils, medical products and instruments, but also in the semi-technical area on surfaces that must be kept extremely clean, that is as free of bacteria as possible, or that are difficult to access for cleaning steps. The small thickness of the equipment is of particular advantage, since the macroscopic properties and the appearance of the underlying material remain virtually unchanged.

The Bacteriostatic according to the invention equipment is particularly advantageous where only extremely thin coatings are possible. For example, the process according to the invention for the preparation ultrathin Coatings on the interior walls of hose and tube systems are used, which in turn only a particularly small diameter, z. B. in mm or even microns range, have (implantable pumping systems, thin Catheter, microbiological and genetic engineering laboratory equipment). The inventive method but is also suitable for coating extremely large surfaces (hulls, technical piping systems, Swimming pools, operating rooms etc.).

The The following examples are intended to illustrate the invention.

I. Preparation of isocyanate-terminated, stellate polyether

When Isocyanate served in all cases a commercial one Isophorone diisocyanate (IPDI: 72% cis and 28% trans isomer), the was distilled before use in vacuo (95 ° C / 0.01 bar) and under inert gas was kept.

at the prepolymer precursors used are commercially available 6-arm polyalkylene ethers (hereinafter polyols) by anionic ring-opening Polymerization from ethylene oxide and / or propylene oxide using of sorbitol as initiator. The used polyol was used to a residual water content of less than 350 before use ppm dried. Remains of the for the preparation of the polyols used alkali hydroxide were bound by neutralization with phosphoric acid.

The Polyol was slowly added via a pump in all preparation examples (about 80 ml / h), so that the reaction temperature is not more than 10 K deviated from the specified temperature.

The Determination of the molecular weight (indicated in each case the number average) was carried out by gel permeation chromatography at room temperature on three columns connected in series (Pillar 1: Waters μ-Styragel 1000 angstroms, I = 30 cm; pillar 2: Waters μ-Styragel 100 angstroms, I = 30 cm; pillar 3: PSS SDV 50 angstroms, I = 60 cm) using tetrahydrofuran as eluent, a Refractometry detector (Waters RI 2410) and using the evaluation software PSS Win-GPC V 4.02. The elution diagrams were evaluated on two gaussian curves adjusted, over the area ratios the proportion of bi- / trimer was determined.

The Characterization of the end groups of functionalized prepolymers and functionalization yield, where indicated, also elemental analysis (sulfur, nitrogen), by IR spectroscopy (v SH, C = O, NH) or by titration (unreacted OH groups).

The Determination of the unreacted OH groups was carried out by reaction the prepolymer with acetic anhydride in pyridine and titration of excess acid (hydrolysis of unreacted Acetic anhydride) with NaOH.

Production Example 1

The used star-shaped Polyether polyol is a 6-arm random poly (ethylene / propylene oxide) with an EO / PO ratio of 80/20 with a molecular weight of 3100 g / mol. Before the implementation gave 0.05% by weight of phosphoric acid to the polyol and heated with stirring 1 h at 80 ° C in a vacuum.

125 ml of IPDI (0.59 mol) were placed in a reactor and heated to 50 ° C. under a protective gas atmosphere. Thereafter, with vigorous stirring, the dried and degassed polyol (20 g, 6.45 mmol) was added Help a peristaltic pump slowly to (about 80 ml / h). After completion of the addition, the reaction mixture was stirred at 50 ° C for a further 60 hours. Excess IPDI was completely distilled off at 100 ° C. and a pressure of 0.001 mbar with the aid of a thin-film distillation apparatus. This gives a star-shaped 6-arm prepolymer having isocyanate groups at the ends of its polymer arms.

Production Example 2

Analogous Production Example 1 was 30 g of a 6-arm statistical Poly (ethylene oxide / propylene oxide) with an EO / PO ratio of 80/20 with a number average molecular weight of 12,000 with 48 ml (0.23 mol) of IPDI reacted. After thin-layer distillation (100 ° C / 0.001 mbar) the isocyanate-terminated star prepolymer was obtained. The proportion of higher oligomers is less than 1% by weight.

Production Example 3

Analogous Preparation Example 1 was 20 g (1.11 mmol) of a 6-arm, random poly (ethylene oxide / propylene oxide) having an EO / PO ratio of 80/20 with a number average molecular weight of 18,000 with 42 ml (0.2 mol) of IPDI reacted. After thin-layer distillation (100 ° C / 0.001 mbar) the isocyanate-terminated star prepolymer was obtained. The proportion of higher oligomers is less than 1% by weight.

II. Preparation of Hydrogel Coatings

When Substrates became glass slides (float glass, quartz glass, standard glass) and hydrophilic silicon wafers used (Si [100]). The substrates were before coating in the ultrasonic bath first in acetone, then in Millipore water and then in isopropanol. All substrates were basically used for Avoid contamination by dust and grease droplets the air in suitable protective containers under a liquid layer kept.

The used water became basic desalted (18 MΩ-cm or better). All solutions were using a 0.05 μ filter of dust and particulate Cleaned impurities. Filtered deionized water is added hereinafter also referred to as Millipore water.

Water-excluded coatings were carried out in a glove box (brown) under an atmosphere having a water content of less than 1 ppm H ₂ O / O ₂ .

1. Aminofunctionalization the substrates

The Purified substrates were allowed to activate in a plasma system of the type TePla 100-E of the company Plasma Systeme 2 minutes in the oxygen plasma treated (pressure: 1 mbar, 50 W). Alternatively, the substrates can also without prior cleaning by 1 hour Storage in a mixture of concentrated ammonia, hydrogen peroxide solution (25 wt .-% in water) and water in the volume ratio 1: 1: 3 at 60 ° C and then rinsing with Water pretreated. The treated substrates were then in stored desalinated water.

to Aminofunktionalisierung was the plasma-treated substrate surface initially with coated with an aminosilian monolayer. For this purpose, the from the Water taken and dry-blown with nitrogen sample into a Glove box transferred. There, the substrates were in a 0.4% (v / v) solution of N- (3- (trimethoxysilyl) -propyl) ethylenediamine stored in dry toluene for 16 h, then washed thoroughly with toluene and before use under a nitrogen atmosphere in the glove box by means of dried a filtered nitrogen stream.

2. Coating of the substrates

All activities carried out under dust-free conditions (clean room conditions).

2.1 General rule

For coating from aqueous medium, the prepolymer was dissolved in a mixture of water and N-methylpyrrolidone in the volume ratio 9: 1 and immediately afterwards with the aid of a spin coater (model: WS-400A-6TFM / lite from the company: SPS) on the prepared according to 1, aminofunktiona laminated glass slide applied. For this purpose, first the non-rotating, dried substrate was completely wetted with the prepolymer solution before the solution was spun off for 40 seconds at a final speed of 4000 rpm. After that, the sample was dry. The type of prepolymer and the concentrations of prepolymer in the solution are given in Table 2: TABLE 2

2.2. Coating off aqueous Medium incorporating zinc oxide nanoparticles (Coating No. 7)

The prepolymer from Preparation Example 2 was prepared in a 0.1% strength by weight suspension of zinc oxide particles (mean particle diameter 8 nm, stabilized with trioxadecanoic acid, prepared according to US Pat DE 101 63 256 dissolved in a concentration of 0.1 g / ml. A glass slide was coated with the suspension thus obtained according to the instructions given under 2.1.

2.3 Coating from aqueous Medium incorporating zinc oxide nanoparticles and silver nitrate (Coating No. 8)

The Preparation of the coating was carried out analogously to the specified under 2.2 Procedure using the prepolymer of Preparation Example 3, wherein the suspension of zinc oxide particles additionally 5 ppm Contained silver nitrate.

2.4 Coating from aqueous Medium under installation of Anoplin (coating no. 9)

The Preparation of the coating was carried out analogously to that specified under 2.1 Procedure using the prepolymer of Preparation Example 3 in a concentration of 10 mg / ml, instead of one Mixture of water / N-methylpyrrolidone a 0.1 mM solution of Anoplin used in water.

III. Investigation of bacteriostatic properties

1. Investigation of colonization by Staphylococcus Aureus (DSM 799)

A slide coated according to II. 2.1 was overlaid with a suspension of Staphylococcus aureus and incubated for 1 h at 37 ° C. Subsequently, the germ suspension was aspirated and the so treated slides washed twice with water. After transfer to sterile 6-well plates, the slides were overlaid with CaSo agar and incubated at 37 ° C for 48 h. Then the number of germs along two parallels was counted microscopically and compared with the reference value after averaging. The reference was a glass slide cleaned with ethanol. The results are summarized in Table 3: Table 3:

2. Investigation of colonization by Pseudomonas aeruginosa (DSM 939)

One after II. 2.1 coated slide was with a suspension overlaid by Pseudomonas aeruginosa and 1 h at 37 ° C incubated.

Subsequently was aspirated the germ suspension and the so treated slide twice washed with water. After transferring to sterile 6-well plates became the slide covered with CaSo agar and 48 h at 37 ° C incubated. Since a quantitative evaluation was not possible, was visually estimated the number of germs and the quality of the coating assessed according to the scale given below. For reference served with a glass slide cleaned with ethanol. The results are summarized in Table 4:

3

Considerably less than control value

2

less than control value

1

Slightly lower than passphrase

0

corresponds to control value

Table 4

3. Examination of the reduction the bacterial colonization

Glass slide, made according to II 2.1, were each diluted with a 20 times diluted culture medium, that with a mixture of gram-positive and Gram-negative bacteria were inoculated for 6 hours at 30 ° C. The slides treated in this way were dried. Subsequently colored one with the slides Safranine O on. The Safranin O bound on the glass slide became extracted with dimethyl sulfoxide and photometrically at a wavelength of 492 nm quantified.

The Difference between the absorption of the dye-containing sample and The absorption of pure DMSO (0 value) corresponds to the amount of on the slide bound Safranins and therefore correlates with the amount of the slides colonizing bacteria. By comparison with an uncoated slide Glass (reference) results in the reduction of biofilm formation in %.

The measurement was carried out as a double determination, ie two samples were tested in parallel and the Mean used to determine the reduction in biofilm formation.

The results are summarized in Table 5. Table 5

4. Investigation of "leaching"

The coated slides Nos. 1 to 7 were incubated in a suspension containing Dermacocci and Bradyrhizobium (10 ⁵ CFU / ml) for 6 days at room temperature. Subsequently, the number of germs in the suspension was determined. In all cases the germ concentration was above 10 ⁷ cfu / ml. Thus, no biocidal substances were released to the germ suspension (CFU = colony-forming units).

5. Investigation of the stability of the coatings across from Aging and opposite mechanical stress their bacteriostatic properties.

One Pressure-sensitive adhesive tape was applied to one of the coatings prepared according to II.2.1 glued on and removed. The coating essentially showed unchanged bacteriostatic properties.

The Coatings obtained according to II.2.1 also showed after 3 months Storage in air at room temperature unchanged bacteriostatic properties.

Claims (23)

Use of star-shaped prepolymers which, on average, at least have four polymer arms A, which are soluble in water per se and wear a reactive functional group R at their free ends, which is complementary to this reactive functional groups R 'or with themselves under bond formation can react, for bacteriostatic equipment of surfaces. Use according to claim 1, wherein the star-shaped prepolymer has on average 6 to 8 polymer arms. Use according to one of the preceding claims, wherein the star-shaped prepolymer a number average molecular weight in the range of 1500 to 100,000 g / mol. Use according to one of the preceding claims, wherein the polymer arms have a number average molecular weight in the range from 200 to 20,000 g / mol. Use according to one of the preceding claims, wherein the polymer arms A are selected among poly-C ₂ -C ₄ -alkylene oxides, polyoxazolidones, polyvinyl alcohols, homopolymers and copolymers which contain at least 50% by weight of N-vinylpyrrolidone in copolymerized form, homo- and copolymers containing at least 30% by weight of acrylamide and / or methacrylamide in copolymerized form, homopolymers and copolymers which contain at least 30% by weight of acrylic acid and / or methacrylic acid in copolymerized form, Use according to claim 5, wherein the polymer arms A selected are among polyethylene oxide, polypropylene oxide and polyethylene oxide / polypropylene oxide block copolymers. Use according to one of the preceding claims, characterized characterized in that the reactive group R is selected under isocyanate groups, (Meth) acrylic groups, oxirane groups, carboxylic acid ester groups and the reactive Group R 'is selected under primary and secondary Amino groups, thiol groups, carboxyl groups and hydroxyl groups. Use according to one of claims 1 to 7, characterized the reactive group R is selected from ethylenically unsaturated, radically polymerizable double bonds. Procedure for bacteriostatic equipment on Surfaces, characterized in that an ultra-thin, hydrogel-forming coating, which are composed of interconnected star-shaped prepolymers, wherein the prepolymers have on average at least four polymer arms A, which seen for themselves soluble in water are on the surface to be coated, and the cross-linking over the ends the polymer arms A takes place. The method of claim 9, comprising: i. apply a solution a star-shaped prepolymer which has on average at least four polymer arms A, seen in isolation soluble in water are and at their free ends a reactive functional group R bear, with this complementary reactive functional groups R 'or with himself can react under binding formation, on the surface to be finished and ii. Causing a linking reaction of the reactive groups R among themselves, forming an ultrathin, hydrogel-forming Coating on a surface applies. Method according to claim 9 or 10, characterized that's on the surface applied amount of prepolymer so chosen is that a coating results in a thickness of less than 1 micron. Method according to one of claims 9 to 11, characterized that the concentration of prepolymer in the solution 0.001 mg / ml to 500 mg / ml. Method according to one of claims 9 to 12, characterized that the surface to be coated was pretreated in such a way that they increased in number functional groups R 'has. Method according to claim 13, characterized in that that the surface in an oxygen-containing plasma or with an ammonia-containing Plasma was treated. Method according to claim 13 or 14, characterized that the surface pretreated with a silane compound having a functional group R ' has been. Method according to one of claims 9 to 15, characterized that you can link the reactive groups R by addition of a compound V1 triggers has at least two reactive groups R 'per molecule, which react with the reactive Groups R of the star-shaped Polymer reacts under bond formation. Method according to one of claims 9 to 15, characterized that you can link the reactive groups R triggers, by adding a sufficient amount of a compound V2, the with a portion of the reactive groups R to form reactive groups R 'reacts, which react with the remaining reactive groups R to form bonds. Method according to claim 17, characterized in that the reactive groups R are isocyanate groups and compound V2 water. A method according to claim 10, characterized in that the group R is selected from ethy lenisch unsaturated, radically polymerizable double bonds and the crosslinking thermally or photochemically triggered. Method according to one of Claims 9 to 16, characterized that he a) first a star-shaped prepolymer 1, which has at least four polymer arms A, seen in isolation soluble in water are and at their free ends a reactive functional group R, applies on the surface to be coated, if necessary performs a partial crosslinking of the reactive groups R, wherein you get a coating, the on their surface still has reactive groups R, b) then at least another star shaped prepolymer 2, which has at least four polymer arms A, seen in isolation soluble in water and at their free ends have a reactive functional group R ', which with the reactive groups R of the star-shaped polymer under bond formation react, applied to the thus treated surface, if necessary crosslinking of the groups R 'triggers and if appropriate, steps a) and b) are repeated one or more times. Method according to claim 17 or 18, characterized that he a) a star-shaped prepolymer 1, which has at least four polymer arms A, seen in isolation soluble in water are and at their free ends a reactive functional group R, applying on the surface to be coated, legs sufficient amount of a compound V2 admits that with a part the reactive groups R react to form reactive groups R ', which react with the remaining reactive groups R to form bonds, where you get a coating, the on their surface having functional groups R ', c) subsequently at least one more star-shaped prepolymer 1 on the thus treated surface apply and re-cross-linking of groups R by addition a connection V2 triggers and if appropriate, steps b) and c) are repeated once or several times. Method according to claim 17 or 18, characterized that you have a flowable composition on the surface which is a star-shaped prepolymer which has at least four polymer arms A, seen in isolation soluble in water are and at their free ends a reactive functional group R, and contains a sufficient amount of a compound V2, the with a portion of the reactive groups R to form reactive groups R 'reacts, which react with the remaining reactive groups R to form bonds. Method according to one of claims 9 to 22, characterized that in the coating a biologically active material and / or Cellular material incorporated.