DE2555624A1 - Coating auxiliary surgical materials - pref sutures with ionically bonded elastomeric block copolymers retaining anti-microbial cpds or dyes - Google Patents

Abstract

Surgical auxiliary material (A) is coated anti-microbially with an ionic block elastomer of formula (I) (where R is 1-15C alkylene, R2 is low alkylene; R3,R4 and R5 are H and lower alkyl, R1 is a liq. prepolymer having mol. wt. 1000-3000 consisting of polyether, silicone, polyurethane or polyamide; Z and Y or OH or isocyanate gps. ZY is urethane gp. formed in condensation of Z and Y; n is integer 10-1000, B- is an anionic polymer and X is an anionic or cationic antimicrobial cpd). Dyed (A) coated with (I; X = anionic or cationic dye gp). and sterile suture material consisting of (A) coated with (I free from X) are also claimed. (A) pref. consist of surgical suture materials, dressings for wounds, fabrics and internal prostheses. Antimicrobial cpd. X added to sterile (I)-coated (A) is retained for a longer duration of use and is released slowly by action of water, blood or tissue-fluids, while bacterial growth in and around suture matl. is inhibited.

Description

Antimicrobial Surgical Supplies and Methods for Its Manufacture The invention relates to antimicrobial surgical auxiliary materials, in particular surgical sutures that have a polymer coating on their surface, in particular have an antimicrobial composition that is not without can further be detached from the suture material by leaching with water.

Germicidal surgical sutures are disclosed in U.S. Patents 861,231, 1,741,893 and 2,751,910 and more recently in U.S. Patent 3,642,003 In the South African patent 724 131 is a surgical suture described having permanent germicidal properties against both gram-negative and also has gram-positive bacteria in that in the suture an insoluble salt composed of a cation of a basic antibiotic and an anion an acidic antibiotic, d. H. Gentamicin oxacillinate, is present It is in of that patent stated that such sutures could be used for five Days are introduced into mice, show no growth of organisms when the Sutures are removed again and placed in a culture medium.

GB-PS 1,248,513 and US-PS 3,632,416 and 3,674,90t coated surgical sutures that incorporate medical agents. A disadvantage of the described suture covers, however, is that they have poor mechanical properties and readily differ from the suture peel off.

The surgical suture material according to the invention has the advantage over this that in South African Patent No.

724 131 described sutures that you can use any anionic or cationic antimicrobial agents can be incorporated into the suture and this during the manufacture of the surgical suture material or during use the suture can cause. After the antimicrobial agent in the surgical Suture material is incorporated, it will be in the for a long period of use Suture strand retained. Through water, blood and tissue fluids slowly remove the antimicrobial compound over an extended period of time surgical sutures leached out.

The invention now relates to a surgical auxiliary material and in particular, a surgical suture made with an ionically bonded elastomeric Block copolymer made from a polyquaternary polyurethane and a polyanionic one Polymer, such as heparin, is coated. The coated surgical sutures can be treated with antimicrobial compounds making one a surgical one Sutures with permanent antimicrobial properties that give the Bacterial growth in and immediately around the suture. That coated Surgical sutures can also be used to make colored sutures to be stained. Instead of surgical sutures, other sutures can be used surgical auxiliary materials such as foils, films, tissues, wound dressings and the like. similarly coated and provided with antimicrobial properties or to be stained.

The surgical sutures according to the invention are any conventional multifilament or monofilament surgical sutures, made of polyester, polypropylene, silk, cotton and linen, for example, and those with an ionically bonded elastomeric block copolymer made of one polyquaternary polyurethane and a polyanionic polymer such as heparin, are coated. The coated suture can be used with success with anionic or cationic antimicrobial compounds and / or anionic or cationic Dyes are treated. The one provided with the antimicrobial properties Surgical sutures are leach resistant and retain their antimicrobial properties Properties in the presence of water or tissue fluids during a significant period Length of time during which bacteria can grow in and around the suture is inhibited.

The stained surgical sutures are for quick Identification suitable for surgical measures involving different types Sutures are used.

The invention therefore relates to an antimicrobial surgical auxiliary material which is characterized in that its surface is coated with an ionic block elastomer of the general formula is coated, in which R is an alkylene group with 1 to 15 carbon atoms, R2 is a low molecular weight alkylene group, R3, R4 and R5 groups selected from hydrogen atoms and low molecular weight alkyl groups, R1 is a liquid prepolymer with a molecular weight of 1000 to 3000, selected from polyethers, silicones , Group comprising polyurethanes and polyamides, Z and Y groups selected from hydroxyl groups and isocyanate groups, ZY the urethane residue formed during the condensation of Z and Y, n an integer with a value from 10 to 1000, B- an anionic polymer and X an anionic one or mean cationic antimicrobial compound.

The preferred antimicrobial surgical accessory materials of the invention are surgical suture threads or strands tied with a polyquadernary Polyurethane elastomers coated with high heparin content and then with selected antimicrobial compounds are treated. The binding of heparin to polymnrisates was published by Yen & Rembaum (J. Biomed. Mater. Res.

Symposium, Volume 1 (1971) pages 83 to 97). Block copolymers made of polyquaternary polyurethane and heparin containing 5 to 20% heparin in U.S. Patent 3,755,218, which is stated to have them Copolymers have non-thrombogenic properties and for coating surgical auxiliary materials such as membranes, Tubes, catheters, Valves, artificial veins and the like. Are suitable in which the formation of blood clots poses a significant problem. It has now been found that these polyquaternary High heparin polyurethane elastomers are a useful substrate capable of binding selected antimicrobial compounds and these compounds releases slowly. Though a wide variety of diverse surgical Auxiliary materials are provided according to the invention with antimicrobial properties The treatment of surgical sutures is a particularly preferred one Embodiment of the present invention so that the following description deals primarily with surgical sutures.

A preferred ionically bonded elastomeric block copolymer which is used according to the invention as a coating material and as a substrate for the antimicrobial compound or the dye is described in US Pat. No. 3,755,218, which is incorporated herein by reference. The mixed polymer formed from heparin and a polyquaternary polyurethane can be given by the following general formula I are shown, in the R eir alkylene group with 1 to 15 carbon atoms, R2 a low molecular weight alkylene group, R31 R4 and R5 groups selected from hydrogen atoms and low molecular weight alkyl groups, R1 a liquid prepolymer with a molecular weight of 1000 to 3000, selected from polyethers, silicones, polyurethanes and groups comprising polyamides, Z and Y groups selected from hydroxyl groups and isocyanate groups, ZP denotes the urethane residue formed during the condensation of Z and Y, n denotes an integer with a value of 10 to 1000 and B denotes heparin. The low molecular weight alkyl groups and alkylene groups given herein contain 1 to about 6 carbon atoms, preferably 1 to 4 carbon atoms.

The general synthesis for the preparation of the polyquaternary polyurethane comprises the reaction of a compound of the general formula II or III Z-R1 -Z (II) or Z-R1-Y (III) with a compound of the general formula IV or V with the formation of an uncharged or neutral polytertiary amino polymer of the general formula ES obtained as an intermediate product in which R, R1, R2, R3, R4 and n have the meanings given above.

The polymer is then treated with a quaternizing reagent of the general formula R5A in which A is an anion, suitably a halogen anion, to form a polymer of the following general formula VII implemented.

The monomeric materials of the general formulas I and II represent preferably liquid prepolymers which have a molecular weight of above about 400 and below the range in which the prepolymer excessively becomes viscous or solid, so that these prepolymers suitably have a molecular weight below 6000 and preferably from 1000 to 3000.

The group R1 can be an aromatic or aliphatic, saturated one or unsaturated hydrocarbon or a polyether, a silicone. (for example a siloxane), a polyamide, a polyurethane or another prepolymer.

The groups Z and Y are selected from groups that coincide with each other Can enter into condensation reactions and generally lead to the formation of condensation resins can be used, such as isocyanate groups-hydroxyl groups (urethane), isocyanate groups-amine groups (Urea), hydroxyl group-carboxyl groups (polyester), amino group-carboxyl groups (Amide) and the like. The urethane bond forming reagents are preferred because they are various Polyisocyanate materials are readily available, not elimination products are formed, and it is readily possible, the properties of the eventual Select and control formed Vorpo-Polymerisats.

Examples of suitable monomeric diisocyanates are benzene-1,3-diisocyanate, Hexane-1,6-diisocyanate, toluylene-2,4-diisocyanate (TDI), toluylene-2,3-diisocyanate, Diphenylmethane-4,4-diisocyanate, naphthalene-1,5-diisocyanate, diphenyl-3,3-dimethyL-4,4 "-diisocyanate, Diphenyl-3,3'-dimethoxy-4,4'-diisocyanate diethyl ether, 3- (diethylamino) pentane-1,5-diisocyanate, Butane-1,4-diisocyanate, cyclohex-4-ene-1,2-diisocyanate, toluidine diisocyanate, isocyanate end groups containing prepolymers, polyaryldiisocyanates and the like, suitable ones commercially higher molecular weight liquid polyisocyanates available are Adiprene L-100 (DuPont), an isocyanate-terminated polybutylene oxide with a molecular weight from about 2000 and Adiprene L-167 (DuPont), an isocyanate terminated Polybutylene oxide with a molecular weight of about 1350.

Liquid polymers with reactive end groups, such as hydroxyl end groups containing polybutadienes containing 20 to 500 or more carbon atoms, or liquid polysiloxanes containing bisphenol A end groups can be obtained by reaction converted to diisocyanates with a diisocyanate such as hexamethylene diisocyanate will. The elastomeric properties increase with the length of the carbon chain of the prepolymer.

The group R1 of the monomeric compounds of the general formulas III and IV can also be an aliphatic group, an aromatic group or one of the prepolymer groups described above. In the case of using a prepolymer diisocyanate, a compound of the following general formula is suitably used as the hydroxy amine material: in which R6 and R7 have low molecular weight alkyl groups, aryl groups such as phenyl groups, aralkyl groups such as benzyl groups, or low molecular weight alkenyl groups, each group m independently of one another whole numbers with a value from 0 to 6, and ml an integer with a value from 1 to about 6 mean.

Examples of such compounds are 3-dimethylamino-1,2-propanediol, 4-diethylamino-1,3-butanediol and 6-dimethylamino-1,4-hexanediol.

In the quaternizing reagent of the formula R5A, the group -R5 represent a hydrogen atom or a low molecular weight alkyl group, while the group A is a halogen such as chlorine, bromine or iodine, an alkyl sulfate such as methyl sulfate or an alkyl iodide such as methyl iodide.

The polymerization reaction can be carried out in bulk or in the presence of a Solvent for the monomers and the polymer product, such as benzene, carried out will. The reaction can take place at room temperature or at elevated temperature up to the reflux temperature. The quaternization reaction will in the presence of a solvent for the tertiary amino polymer and for the formed quaternary salt carried out, for example in the presence of tetrahydrofuran, Acetone, dioxane, dimethylformamide, diaminoheptane or mixtures thereof.

The quaternized elastomeric polymer is further treated with anionic polymers or salts thereof, such as polystyrene sulfonate, polyacrylates and the like, and in particular with heparin or its alkali metal or ammonium salts to form viscoelastic, ionically bound block polymer salts of the following general formula implemented, in which B- is an anionic polymer, preferably heparin, and R, R1, R2, R3, R4, R5, Z, Y and n have the meanings given above.

The heparin content of the block copolymer can be between 5 wt vary up to about 20% by weight. Materials with a higher heparin content can also be used are produced, but it has been shown that these products have a lower Have degree of elasticity. Materials with lower heparin content are common Soluble organic solvents, while materials containing more than 15 e heparin contained in polar solvents such as tetrahydrofuran, dimethylformamide (DMF). Hexamethylphosphoramide (Hexametapol) and in particular mixtures thereof with 1-methyl-2-pyrrolidone, are soluble. For materials with the highest heparin content is a small amount from about 0.01 to 5 e of a primary or secondary amine such as dibutylamine in dimethylformamide necessary to achieve complete solubility.

The block polymer is formed by the ionic reaction of the quaternized Elastomers (chloride counterion) with sodium heparin with elimination of sodium chloride. Thus, the amount of chloride after the reaction is very small. The reaction just follows by combining the elastomer with sodium heparin, preferably in the form of separate solutions in a solvent, in particular in a methanol / water mixture (50:50 volume / volume).

The copolymers of polyquaternary polyurethane and the anionic polymer, to which an anionic or cationic antimicrobial compound or dye group has subsequently been bonded, as will be explained below, are suitably represented by the following general formula reproduced, in which X stands for said antimicrobial compound or the dye group.

The binding of the antimicrobial compound or dye group to the heparin elastomer is shown in the formula with a dotted line, since the true binding mechanism is not known. Though by theoretical considerations If the invention is not to be limited, there is one possible mechanism that the heparin elastomer contains free, positively charged nitrogen atoms and free, can have negatively charged sulfo groups that bind anionic (X-) or cationic (X +) antimicrobial compounds or dye groups are available stand. According to another possible mechanism, the addition of the antimicrobial Dissociate the heparin elastomer by means of or the dye group, after which a complex of heparin and the antimicrobial compound or of heparin and the dye is precipitated in the polymer matrix and / or incorporated therein. Although one of the two mechanisms can occur or a different mechanism can exist is knowledge of the true mechanism for understanding and it is not necessary to practice the present invention.

The mixed polymer of the polyquaternary polyurethane and heparin binds basic antimicrobial agents such as gentamycin or benzethonium chloride, and acidic antibiotics like the peaicillins.

Other examples of suitable antimicrobial agents used by the polyquaternary polyurethane elastomers with high heparin content and retained are slowly released after the surgical suture is implanted, are the cephalosporins, such as cephalolexin, cephaloglycine, cephaloridin, cephalothin; the 6-substituted penicillanic acids, such as penicillins G, N and V, methicillin, Oxacillin, as well as vancomycin, neomycin, erythromycin, streptomycin, cycloserine, tetracycline, Aureomycin, terramycin (oxytetracycline), gentamycin and polymyxin B. Particularly preferred is neomycin sulfate.

The basic fiber on which the elastomeric heparin polymer coating is applied any non-absorbable surgical suture material, made of, for example, nylon, silk, polyester and cotton, or any absorbable surgical suture material, such as catgut or one made from homopolymers and copolymers of glycolide and lactide.

Although there are basic fibers with the elastomeric heparin polymer can be coated, the adhesion of the coating to certain fibers, such as for example polypropylene fibers, relatively poor, so the application of such coated fibers is limited accordingly.

The elastomeric polymer is in a suitable solvent dissolved and applied from the solution to the surgical suture material. According to a The preferred method is to immerse the surgical suture material in a solution, which is about 1.0 to about 50% by weight of the polymer, preferably about 3 to about 30 % By weight of the polymer, in dimethylformamide as a solvent. The surgical one Sutures are dried to remove the solvent, leaving a more uniform Coating of the elastomeric heparin polymer remains. By repeating Immersion and repeated application can be arbitrary many overcoats can be applied sequentially on the surgical sutures until the desired Degree of Polymerisatauf acquisition is reached. In general, 0.1 to 25% by weight of the polymer, based on the surgical suture material, an effective polymer uptake It can of course with advantage also larger or smaller amounts of the polymer may be applied, although amounts in excess of 25% will stiffen the surgical Suture material and to a certain adhesion of adjacent threads of the wound sutures can lead to each other.

The coated surgical sutures are capable of large To bind a variety of antimicrobial compounds or agents. That coated Surgical sutures can be sterilized, packaged, and neutralized up retained for use at what time a selected antimicrobial Means can be applied easily.

Such surgical sutures make it possible to choose the most effective one antimicrobial agent for a special purpose.

Alternatively, one can select the surgical sutures with one Treat antimicrobial agents, sterilize, package and see later Keep use. In case the selected antimicrobial agent is applied by the Sterilization technology is compromised, one can use the coated surgical one Sterilize the sutures before applying a sterile antimicrobial agent and aseptically package the treated surgical sutures.

Such mechanical measures are customary and readily available to the person skilled in the art common. The sterilization can be done, for example, that the material treated with ethylene oxide, irradiated with the help of a cobalt-60 radiation source or otherwise treated.

The selected antimicrobial agent is suitably used in shape an aqueous solution applied to the coated surgical suture. The coated surgical suture becomes easy for a period of time immersed in the solution from a few seconds to a few minutes or more, then removed and either dried or directly, i.e. without drying, used. The concentration of the antimicrobial agent in the treatment solution can be in Depending on the solubility of the particular compounds, although im generally concentrations in the range of about 1.0 to 10% by weight are satisfactory although lower or higher concentrations are used if desired can be.

The elastomeric heparin polymer can also be applied to any prosthesis Applied for surgical uses where surgical Auxiliary materials or support devices are necessary, are suitable, for example Heart valves, woven or extruded tubular structures that are used to restore serve of arteries, veins, ducts or esophagus; woven or knitted fabrics, those used for the surgical repair of hernias and for the support of damaged ones Serve livers, kidneys, and other internal organs; Nails, screws, reinforcement plates and artificial tendons or cartilage materials. The on the surface of in this Antimicrobial applied to treated surgical ancillary materials Preparations are retained by the elastomeric heparin polymer and slowly released.

Other surgical aids on which the elastomeric heparin polymer Can also be used as a cover, include bandages and other wound dressings, which are used for topical application purposes. Alternatively, you can use the polymer cast into a thin polymer film, sterilized, packaged and used as a wound dressing As in the case of surgical sutures, this can be antimicrobial Material at the time of manufacture or at the time of use in the elastomeric heparin polymer are incorporated.

In addition to the antimicrobial material, you can put it on the surface The elastomeric coating or film also includes a local anesthetic such as cinchocaine hydrochloride Instruct.

The with the polymer from the polyquaternary polyurethane and the Heparin coated surgical sutures are also great for staining with anionic and cationic dyes and can therefore be used in one large variety of different hues can be colored.

The dyes can be used alone or in conjunction with one or more antimicrobial compounds are applied. The dyes are usually by dipping, padding, spraying or the like from aqueous solutions at room temperature drawn onto the surgical suture material.

The following examples serve to further illustrate the invention. It is understood, however, that a number of alternative, equivalent Reagents and conditions are readily understood. The antimicrobial activity the surgical sutures of the invention have been used in vitro using the following test method: Standard test method for evaluation the in vitro effectiveness of the antimicrobial surgical sutures organisms: Bacillus subtilis ATCC 19659 Escherichia coli ATCC 10536 Pseudomonas aeruginosa ATCC 15442 Staphylococus aureus ATCC 6835 Media: trypsin soy broth (Difco) + 0.4 % Ionagar 2 S Procedure: 1. Spread trypsin soy agar plates (Difco) with the appropriate organism and incubated overnight at 370C. Then washes man remove the cells from the surface with the help of glass beads and saline. Afterward the optical density of each suspension is adjusted to 0.1 2. Bring tubes filled with trypsin soy broth plus 0.4% ion agar 2 S at one temperature from 45 to 500C in a water bath in equilibrium. Then 10% (or 2.5 ml per 25 ml trypsin soy broth plus 0.4% Ionagar 2 S) beef serum and 1% (or 0.25 ml) of the adjusted bacterial suspension into the medium and mix slowly by shaking with your hand. 8 ml of this inoculated medium are then per plate pipetted on and allowed to cool.

3. Then 1.5 cm long pieces of potential antimicrobial become more surgical Sutures applied to the cooled agar and kept for 24 hours 370C incubated. Each test is carried out 3 times. No more per plate applied as 4 pieces of the antimicrobial surgical suture, wherein these pieces are spaced equidistant from the edges and the center. After incubation, precise zone determinations are made using vernier calipers carried out. Here, the entire zone width is at right angles to the longitudinal axis of the surgical sutures, which is the diameter of the surgical sutures includes, for sure.

Example 1 50 g of a polybutylene oxide diisocyanate (ADIPRENE L 167, commercially available from E.I. DuPont de Nemours & Co., Inc., Wilmington, Delaware 19898, USA, which contains between 6.15 and 6.55% free isocyanate) in 500 ml of benzene and sets the material for 48 hours at the reflux temperature with 4.6 g of vacuum distilled 3-methylamino-1,2-propanediol. One pursues them Reaction using the infrared spectrum. The disappearance of the OH peak at / = 3480 cm as well as the NCO absorption peak at v = 2280 cm 1 upon termination of the reaction. After 48 hours, 300 ml of benzene distilled from the reaction flask and the residue to remove the remainder Benzene freeze-dried. The yield of the condensation product is 56.2 g.

Example 2 30 g of the rondensation product from Example 1 are dissolved in 200 ml of tetrahydrofuran. A concentrated solution of hydrochloric acid is then added (8 g of 37 to 38% strength by weight HCl), which is a stoichiometric excess of 100 % is equivalent to. The solution is stirred at room temperature overnight and then precipitated with 1500 ml of n-hexane. Then wash well with water to remove the unreacted HCl.

The quaternized polymer is overnight in vacuo at 50 ° C dried.

Example 3 25 g of the quaternized described in Example 2 are dissolved Polymer in 250 ml of methanol. It is slowly added to this mixture while stirring and 150 ml of distilled water to form a homogeneous solution (solution A).

Dissolve 5 g of sodium heparin in 125 ml of distilled water.

175 ml of methanol are slowly added to this solution with stirring in this way forms a homogeneous heparin solution (solution B). Then you give them Polymer solution (solution A) quickly and with vigorous stirring to the heparin solution (Solution B). The precipitate formed is collected, washed with water and dried in vacuo at room temperature.

The yield after drying is 6.2 g. The heparin content of this Product is 16% by weight.

Example 4 Treating 60 feet of polyester fiber sutures with a thread size of 2/0 in a laboratory coater with a solution of 0.5 parts by weight of the heparin polymer prepared according to Example 3 in 15 parts by weight of dimethylformamide. The coated suture contains thread after drying 7.2% by weight of the polymer and shows good handling and knotting properties.

A portion of the coated suture material is immersed for 1 hour in a solution obtained by dissolving 2.5 parts of streptocin sulfate in 50 parts of distilled water. The suture is then removed, placed in a flask and extracted with stirring with distilled water as follows: (1) 15 minutes with 500 ml distilled water (2) 15 minutes with 500 ml distilled water (3) 15 minutes with 500 ml distilled water Agitation by shaking (4) overnight for 17 hours with 500 ml of distilled water (5) Brief rinsing under running distilled water.

The suture is then dried by irradiating it with a Cobalt-60 source sterilized and in vitro for antimicrobial activity examined. For comparison purposes, two control sutures made from polyester fibers are used used. One control material does not use the high heparin elastomer coated, but otherwise treated in the same way. In the case of the second control material is a suture made of polyester fibers that is similar to that in example 3 described elastomers coated with a high heparin content but not treated further has been.

The results obtained are summarized in the following table. The zones of inhibition are given in centimeters.

Sutures B. E. Ps. S.

subtilis coli aeruginosa aureus sutures coated with the Elastomers with a high heparin content. Treated with aqueous 0.55 0.19 no content 0.44 streptomycin sulfate. Exercise zones also trawl in the manner described distilled water. Uncoated control suture. Agile with aqueous Streptomycin sulfate. no khi- no no inhi- no in-extracted while about beer inhibition 18 hours with distillation zones beer Zones zoned water.

Suture material coats no in-no in-no in-no in-mit the elastomer with a high heparin content. change zones zones zones No further treatment.

After seven days of implantation of the sutures described above in rats there were no significant differences in terms of tissue reactions determine.

Examples 5 to 12 The procedures of the example are repeated 4 with replacement of the streptomycin sulfate used in Example 4 by different ones anionic and cationic antimicrobial compounds.

Examples 5 through 7 use the same coated suture used as in Example 4. In Examples 8 to 12, an identical suture is used used, but which has a slightly weaker coating. The effectiveness of the various antimicrobial compounds after extraction with water can be seen from the following data. Example coating, antimicrobial Mean Mean size (cm) of zone of inhibition wt% B.S. E.C. P.A. S.A.

5 7.2 neomycin sulfate 1.78 0.99 0.42 1.25 6 7.2 tetracycline hydrochloride 1.78 0.58 0 1.19 7 7.2 Potassium penicillin 0.28 0 0 0.85 8 6.8 Gentamicin sulfate 1.44 * * * 9 6.8 Oxytetracycline dihydrate 0.30 * * * 10 6.8 Polymixin B sulfate 0.29 * * * 11 6.8 Sodium Cephalothin 1.48 * * * 12 1.0 Neomycin Sulphate 1.12 * * * B.S. = Bacillus subtilis P.A. = Pseudomonas aeruginosa E.C. = Escherichia coli S.A. = Staphylococcus aureus * not determined For all examples 5 to 12 a similar results Well treated but uncoated control suture does not have a zone of inhibition.

Example 13 Subject a sample of the coated suture to which has been treated according to Example 5 with neomycin sulfate, for a longer period of time Water extractions in 1.5 liters of distilled water each time as follows: Extractions for 9 to 24 hours; Extractions for 1 to -120 hours; Extractions for 3 to 168 hours. After completion of these extraction processes, the treated one gives surgical sutures have a zone of inhibition for Bacillus subtilis of 1.26 cm. A similarly treated but uncoated control material shows no antimicrobial after an initial extraction for 24 hours Properties.

Examples 14-21 A number of studies are included Application of a modified extraction technique to sutures made with antimicrobial materials have been treated, some of which are related to the water extraction are more sensitive than those in the previous examples used. All of the following examples are surgical Sutures around a 2-0 braided polyester suture that is after the procedure of Example 4 coated with about 7 wt .-% of the heparin polymer has been.

The sutures are made by irradiating them with the Cobalt-60 bomb sterilized and then placed in a 5% aqueous solution of the selected antimicrobial Means immersed for 1 hour at room temperature. Treated surgical Sutures are used before extraction and after one hour, two hour and four hours of extraction in distilled water for antimicrobial activity examined. The following results are obtained here: For example Antimicrobial agent Mean size (cm) of the zone of inhibition extraction- 0 1 2 4 time hours hours hours hours 14 neomycin sulfate 1.62 0.74 0.71 0.70 15 rifamycin 1.79 1.24 1.24 0.89 16 benzethonium chloride 1.39 0.76 0.71 0.67 17 cephaloridin 3.77 1.19 0.58 0.13 18 Sodium oxacillin 2.91 0.62 0 0 19 Dihydrostreptomycin sulfate 1.71 0.23 0 0 20 Disodium Carbenicillin 2.31 0.20 0 0 21 Sodium Furadantin 1.15 0 0 0 From the above numerical values it can be seen that some of the antimicrobials are more prone to water leaching than others. With the exception of Example 21, however, all of the surgical sutures show some antimicrobial effect after extraction for 1 hour, whereby It is believed that such surgical sutures are a significant amount of one have lasting antimicrobial activity.

Example 22 Healthy, young, adult Sprague-Dawley rats are anesthetized removes the hair from the back of the rats and with the help of a hair clipper prepares the skin for surgical treatment. Under sterile conditions a small hemostat is inserted through a 0.5 cm incision 6 inches long thread of the Example 5 suture on the right Side of the rat into the dorsal subcutaneous tissue. One with the antimicrobial Medium treated but uncoated control thread appears on the left Page introduced. The incisions are closed and the rats are put into theirs appropriately labeled cages returned.

After appropriate time intervals, the animals are exposed to carbon dioxide killed, after which the dorsal skin dissected and the exposed sutures underneath be removed under aseptic conditions. With separate dry, Sterile tweezers and scissors pry the outer ends of the thread (about 0.6 cm (1/4 in inch)) cut off and discarded. The remaining thread is cut into 1.5 cm long pieces cut up and without re-sterilizing for residual antimicrobial activity using the in vitro method described above using Bacillus subtilis as an indicator organism. The ones given in the table below Test results clearly show the permanent antimicrobial effect, the is achieved with the surgical sutures coated according to the invention.

Implantation time zone of inhibition (cm) (days) Sutures uncoated according to example control material 13 O (not implanted) 2.09 2.22 3 0.31 no inhibition zone 7 0.46 no inhibition zone 14 0.44 no inhibition zone 21 0.14 no inhibition zone 28 0.04 no zone of inhibition Example 23 A braided nylon suture is coated (Size 2/0, undyed, not waxed) as described in Example 4 with the elastomer made from heparin and the polyquaternary polyurethane. After three passes the coating device resulted in a polymer uptake of 8.01 % based on the weight of the suture.

One dips a thread of the coated nylon suture with a Length of 20 cm for 1 hour at room temperature in a 5% (weight / volume) Neomycin sulfate solution. After removal, the thread is cut three times in 500 ml of distilled water for 15 minutes, after which the thread is placed in Soak 500 ml of distilled water. Then the thread will last for a few seconds kept under running distilled water and then dried at room temperature.

Then parts of the suture are made using Bacillus subtilis was examined as a test organism for the remaining antimicrobial activity. The mean of the zones of inhibition was 1.44 cm. For comparison purposes, a normal uncoated sample of nylon suture in neomycin sulfate solution soaked and then soaked with water under the same conditions washed, as used for the coated suture. This control suture shows no zones of inhibition compared to the test organism.

Example 24 Treating braided silk sutures (size 2/0) uncolored, not waxed) in a manner similar to that described in Example 23 with two coatings from a polymer solution.

The polymer uptake is 2.83%, based on the weight of the suture material. The treatment with a 5 Eigen neomycin sulfate solution and the subsequent extraction with water are carried out in the same way as described in Example 23.

The middle zone of inhibition against the test organism Bacillus subtilis results in 2.06 cm.

For comparison purposes, a silk control suture material without a polymer coating gives but otherwise treated in the same way with the neomycin sulfate solution and with Water was extracted, a mean zone of inhibition of 2.09 cm.

Example 25 1 g of the heparin elastomer described in Example 3 is dissolved in 20 ml of dimethylformamide, 2 ml of dibutylamine and 1 ml of hexamethylphosphoramide and pour the solution onto a glass surface to form a thin film. Man removed the solvent at 100 ° C in an oven and then pulls the film off the smooth Glass surface. The film or the foil is immersed in an aqueous (4% strength by weight) tetracycline hydrochloride solution immersed, air-dried at room temperature, packaged and irradiated sterilized with a cobalt 60 source. The thin films obtained in this way or films are suitable for dressing skin wounds and burns.

Example 26 A braided polyester suture is coated (Size 2/0, white) according to the procedure described in Example 4 with the heparin polymer. The coated suture is made by irradiating with a Cobalt 60 bomb in usually sterilized, after which parts of the coated fibers in different, dye solutions described below are immersed.

For comparison purposes, a section of an uncoated Sutures used. The samples are taken from the dye liquor and rinsed and rated for their coloration. The results obtained are as follows Table compiled: Dye solution coated uncoated sutures tes control suture material Rhodamine B (0.1 g in 20 ml distilled water) dark pink pale pink tinted bromothymol blue (0.1 g in 20 ml of distilled water) yellow colorless Methylene blue (0.1 g in 20 ml of distilled water) dark blue, slightly blue tinted Eriochrome black T (0.1 g in 20 ml of distilled water) reddish brown colorless bromocresol green (0.1 g in 20 ml of distilled water, whereby the insoluble residue is filtered off becomes) green colorless azure A (0.1 g in 20 ml of distilled water, the insoluble The residue is filtered off) quinizarine sulfonic acid tinted dark purple, pale blue (0.1 g in 20 ml of distilled water, adding 10 drops of 0.1 N NaOH solution, more insoluble Filtered off residue) orange-brown colorless thyitol blue, (0.1 g in 20 ml of distilled Water, addition of 10 drops of 0.1 N NaOH solution, insoluble residue filtered off) yellow colorless pararosaniline hydrochloride (0.1 g in 20 ml of distilled water, addition from 10 drops of 0.1 N NaOH solution, insoluble residue disappears - dark purple, pale blue filtered) tinted The following dyes were made in the same manner examined and assessed. In all cases, the fibers of the invention are in stained a faint to medium shade while the uncoated fibers show no noticeable color: phenol red, uranine, paraxylenol blue, hematein, methyl orange, Methyl red, phenolphthalein disodium salt and bromophenol blue.

Although the above examples are a preferred embodiment of the invention explain where the coating of the suture material is made from a copolymer polyquaternary polyurethanes and heparin, these examples serve only the Explanation and not intended to represent a limitation of the invention. However, there are various changes, modifications and alternatives to the polymer compositions, the antimicrobial compounds and the dyes are readily available to the person skilled in the art well known and accessible without departing from the scope of the invention.

Claims (29)

Claims 1. Antimicrobial surgical auxiliary material, characterized in that its surface is coated with an ionic block elastomer of the general formula is coated, in which R is an alkylene group with 1 to 15 carbon atoms, R2 is a low molecular weight alkylene group, R3, R4 and R5 groups selected from hydrogen atoms and low molecular weight alkyl groups, R1 is a liquid prepolymer with a molecular weight of 1000 to 3000 selected from polyethers, silicones, Polyurethanes and polyamides comprising group, Z and Y selected from hydroxyl groups and isocyanate groups, ZY the urethane residue formed during the condensation of Z and Y, n an integer with a value of 10 to 1000, B- an anionic polymer and X an anionic or mean cationic antimicrobial compound. 2. Surgical auxiliary material according to claim 1, characterized in that that it is the anionic polymer polystyrene sulfonate, polyacrylate and / or heparin contains. 3. Surgical auxiliary material according to claim 1, characterized in that that it is an antimicrobial compound neomycin sulfate, tetracycline hydrochloride, Potassium penicillin, streptomycin sulfate, gentamycin sulfate, oxytetracycline dihydrate, Polymixin B sulfate, sodium cephalothin, rifamycin, benzethonium chloride, cephaloridine, Contains sodium oxacillin, dihydrostreptomycin sulfate and / or disodium carbenicillin. 4. Surgical auxiliary material according to claim 3, characterized in that that it contains heparin as an anionic polymer. 5. Surgical auxiliary material according to claim 1, characterized in that that it is in the form of a surgical suture. 6. Surgical auxiliary material according to claim 1, characterized in that that it is in the form of a wound dressing. 7. Surgical auxiliary material according to claim 1, characterized in that that it is in the form of a tissue. 8. Surgical auxiliary material according to claim 1, characterized in that that it is in the form of a prosthesis. 9. Surgical suture material according to claim 5, characterized in that that it is an anionic polymer B-heparin and an antimicrobial compound Contains neomycin sulfate. 10. Colored surgical auxiliary material, characterized in that its surface with an ionic block elastomer of the general formula is coated, in which R is an alkylene group with 1 to 15 carbon atoms, R a low molecular weight alkylene group, 2 R37 R4 and R5 groups selected from hydrogen atoms and low molecular weight alkyl groups, Ra a liquid prepolymer with a molecular weight of 1000 to 3000 selected from polyethers, silicones, Group comprising polyurethanes and polyamides, Z and Y groups selected from hydroxyl groups and isocyanate groups, ZY the urethane residue formed during the condensation of Z and Y, n an integer with a value from 10 to 1-000, B- an anionic polymer and X an mean anionic or cationic dye group. 11. Surgical auxiliary material according to claim 10, characterized in that that it is the anionic polymer polystyrene sulfonate, polyacrylate and / or heparin contains. 12. Surgical auxiliary material according to claim 10, characterized in that that it is in the form of a surgical suture. 13. Surgical auxiliary material according to claim 10, characterized in that that it is in the form of a wound dressing material. 14. Surgical auxiliary material according to claim 10, characterized in that that it is in the form of a tissue 15. Surgical suture material according to claim 12, characterized in that it contains B-heparin as the anionic polymer. 16. Sterile surgical suture material, characterized in that its surface is coated with an ionic block elastomer of the general formula is coated, in which R is an alkylene group with 1 to 15 carbon atoms, R2 is a low molecular weight alkylene group, R3, R4 and R5 groups selected from hydrogen atoms and low molecular weight alkyl groups, R1 is a liquid prepolymer with a molecular weight of 1000 to 3000 selected from polyethers, silicones, A group comprising polyurethanes and polyamides, Z and Y groups selected from hydroxyl groups and isocyanate groups, ZY denotes the urethane residue formed during the condensation of Z and Y, n denotes an integer with a value of 10 to 1000 and B denotes an anionic polymer. 17. Surgical suture material according to claim 16, characterized in that that it is an anionic polymer polystyrene sulfonate, a polyacrylate and / or Contains heparin. 18. Surgical suture material according to claim 16, characterized in that that it contains heparin as an anionic polymer. 19. A method for producing an antimicrobial surgical auxiliary material, characterized in that the surface of the surgical auxiliary material with a solution of an ionic block elastomer of the following general formula brings into contact, in which R an alkylene group with 1 to 15 carbon atoms, R2 a low molecular weight alkylene group, R3, R4 and R5 groups selected from hydrogen atoms and low molecular weight alkyl groups, R1 a liquid prepolymer with a molecular weight of 1000 to 3000 selected from polyethers, silicones , Polyurethanes and polyamides comprising groups, Z and Y groups selected from hydroxyl groups and isocyanate groups, ZY the urethane residue formed during the condensation of Z and Y, n an integer with a value of 10 to 1000 and B- an anionic polymer, the surgical one Dries auxiliary material to form a coating of the ionic block elastomer on the surgical auxiliary material, and then brings the coated surgical auxiliary material into contact with an anionic or cationic antimicrobial compound. 20. The method according to claim 19, characterized in that as anionic polymer polystyrene sulfonate, a polyacrylate and / or heparin is used. 21. The method according to claim 19, characterized in that one Solution of the ionic block elastomer in an organic solvent used 22. The method according to claim 21, characterized in that as organic Solvent dimethylformamide used. 23. The method according to claim 19, characterized in that the coated surgical auxiliary material with an aqueous solution of the antimicrobial Brings connection in touch. 24. The method according to claim 19, characterized in that as anionic polymer heparin is used. 25. The method according to claim 24, characterized in that as uses antimicrobial compound neomycin sulfate. 26. The method according to claim 25, characterized in that as surgical accessory a surgical suture is used. 27. The method according to claim 25, characterized in that as surgical supplies used a wound relatives. 28. The method according to claim 25, characterized in that as surgical auxiliary material uses a tissue. 29. The method according to claim 25, characterized in that as surgical supplies insert a prosthesis.