Combination antibiotic/antibiotics polymer

 

The invention relates to polymer compositions of antibiotics and can be used in medicine and veterinary medicine. The polymer component of the proposed combination is homogeneous polymer blend of one or more hydrophobic polymers from the group of polyesters, methacrylic acid, polyesters of acrylic acid, copolymer of esters of methacrylic acid and esters of acrylic acid and one or more hydrophilic polymers from the group of polyethers. In the specified polymer mixture suspended one or more slightly soluble in water antibiotics of the aminoglycoside group, lincosamide, tetracycline and quinolone antibiotics. If necessary in a mixture of added soluble in water, the antibiotic of the aminoglycoside group, lincosamide and tetracycline antibiotics and, if necessary, organic medicinal excipients. The content of the hydrophilic polymer in a homogeneous polymer mixture is from 0.1 to 60 wt.%. The polymer composite of antibiotics in physiological conditions provides a continuous release of antibiotics for a period of time from several days to several weeks and is suitable for struck the I. The polymer composite of antibiotics applicable to the manufacture of fibers, films and molded articles. 23 C.p. f-crystals, 1 table.

The invention relates to combination antibiotic/antibiotics polymer, which in physiological conditions provides a continuous release of antibiotics for several days and can be used in medicine and veterinary.

In medicine and veterinary medical products of the polymers used in the form of drains, catheters, covering films and nets as temporary or durable implants for aspiration of secretion, washing, coating and fixing. The problem is that microorganisms, in particular, drains and catheters can be moved along the data of polymer binders in the body and thus cause local infections that may spread in the body. Similar problems arise with the introduction of tabs. This microorganism can likewise penetrate along the insertion of the pin into the body. When dental implants are known issues with infection at implant surfaces. Therefore, when the medical use of such implants the need for prevention is asimi antibiotics. The systemic use of antibiotics is complicated by a number of problems. To systematically provide anti-microbial active concentrations of antibiotics, requires relatively high doses of antibiotics. Because of this, in particular, in the case of aminoglycoside antibiotics and tetracycline because of their proxicast or ototoxicity may have the unintended violations. So the idea arose to suppress infections by local application of antibiotics, as this can be achieved by effective local concentration of antibiotics in reducing high systemic concentrations of antibiotics.

Preparation and application of polymer composites of antibiotics is already years the subject of intense research, the result of which was a number of patents. So Shepherd and Gould proposed a coating of catheters with hydrophilic polymethacrylates and polyacrylates, which are made of non-specific antibiotic for treatment of infections (I.e.Shepherd, F. E. Gould: Catheter: 03.03.1971, US 3566874). Also Shepherd and Gould belongs described in 1970 retardery system based on hydrophilic hydroxyethylacrylate and hydroxymethylation, which was depolimerization obtaining molded products, highlighting rowanna releasing the drug. 31.12.1974, US 3857932). Klemm described polymer particles based on polymethacrylate and polyacrylate for the treatment of osteomyelitis (K. Klemm: Surgical synthetic polymeric material and a method of treatment of osteomyelitis. 13.05.1975, US 3882858). These polymer particles were impregnated with gentamicin or another antibiotic. Gross and others have suggested getting a bone cement containing gentamicin (A. Gross, R. Schaefer, S. Reiss: Composition of bone cement containing gentamicin. 22.11.1977, US 4059684). As auxiliary substances readily water-soluble salts such as sodium chloride, potassium chloride, sodium bromide and potassium bromide were added to a mixture consisting of a powdered copolymer of methyl methacrylate and methyl acrylate, methyl methacrylate hydrochloride gentamicin and/or sulfate gentamicin. This mixture was polymerizable under the action of the peroxide. Easily soluble salts were dissolved after the introduction of bone cement in the physiological environment and left cavity. Batich and others described a new system release based copolymers synthesized using acid monomers, which are swollen at pH value of 8.5, which ensured the release included pharmaceutically active substances (C. D. Batich, M. S. Cohen, K. For number of other works were antimicrobial coating medical devices antibiotic polymer systems. So Conway and others, have developed a polymer matrix made of silicone, which has been introduced water-soluble active substances on the basis of nitrofuran (A. J. Conway, P. J. Conway, R. D. Fryar Jr.: Supporting the release bactericidal cannula. 16.11.1993, US 5261896). Application form the matrix polymer from the group of polyurethanes, silicones and biodegradable polymers, in which the suspended mixture of silver salts and chlorhexidine, it was suggested to get a stable infections of medical devices (C. L. Fox Jr., S. M. Modak, L. A. Sampath: Resistant to infection compositions, medical devices and surfaces and methods for their production and application. 28.05.1991, US 5019096). Solomon, Byron and Parke suggested that such anti-infective systems based on polyurethane and dispersed therein chlorhexidine (D. D. Solomon, M. P. Byron: anti-infective and antithrombotic medical products and the way they are received. 19.09.1995, US 5451424; D. D. Solomon, M. P. Parke: anti-infective and antithrombotic medical products and the way they are received. 13.01.1998, US 5707366; D. D. Solomon, M. P. Parke: anti-infective and antithrombotic medical products and the way they are received. 13.01.1998, US 5165952). These systems can be processed from the melt by extrusion in a molded product. The composition of the antibiotic, seanie composition. 29.07.1984, US 4603152). As polymers have been proposed a copolymer of Acrylonitrile, butadiene and styrene, polyvinyl chloride, polyesters, polyurethanes, block copolymers of styrene and rubber, which made the oligodynamic active metals to suppress infections. Elastomers can also be treated with antibiotics. So Allen received the combination of active substances and elastomer by mixing and introducing active substances in the rubber masterbatches (D. L. Allen: Elastomeric composition containing therapeutic agents, and the products. 28.05.1991, US 5019378). Masterbatches consisted of rubber, mica and titanium dioxide. A coating of antibiotics, consisting of a mixture of rifamycin and minocycline dispersed in the polymer, the proposed Raad and Darouiche (I. I. Raad, R. O. Darouiche: Antimicrobial coated medical implants. 08.06.1993, US 5217493). The polymeric material more not characterized. DeLeon and others have proposed a method for coating antibiotics implant, which is designed for coating the first surface was covered with silicone oil (J. DeLeon, I. N. Ferguson, D. S. Skinner Jr.: A method of manufacturing antimicrobe coated implants. 28.03.1990, US 4952419). Silicone oil in the second stage inflicted porono coating based on silicone oil and polyester methacrylic acid, which have been derived from the solution of the silicone oil and polyester methacrylic acid in turpentine oil, n-decane, tetrachloride, butane-2-one, 1,4-dioxane, ethoxyethanol and toluene (Century Takigawa: Covering solution containing silicone oil and polymethacrylates. 24.1998, US 5721301). Mustacich and others describe antimicrobial polymer combination in which fatty acids and salts of fatty acids as biocidal reagents included in the applicable medical polymers (R. V. Mustacich, D. S. Lucas, R. L. Stone: Antimicrobial polymeric composition. 30.10.1984, US 4479795). Interesting cover composition was proposed Whitbourne and Mangan, for which the Quaternary ammonium compounds as antimicrobial reagents were introduced into the water-insoluble polymer, for example an ester of cellulose (R. J. Whitbourne, M. A. Mangan: Covering composition containing pharmaceutical agents. 11.06.1996, US 5525348). The number of known patents Friedmann and others describing the receipt of dental varnishes (M. Friedmann, D. Steinerg, A. Soskolne: Constantly releasing pharmaceutical composition. 11.06.1991, US 5023082; M. Friedman, A. Sintov: Liquid polymer composition and method of application. 03.11.1992, US 5160737; M. Friedman, A. Sintov: Dental varnish composition and method of application. 19.07.1994, US 5330746; M. Friedman, A. Sintov: Dental lacquer composition is shown patents similar in content and describe as significant antimicrobial agents Quaternary ammonium salt. In the patents described varnishes and polymer solutions for their production, which mainly consist of the following components: copolymer based on methacrylic acid and esters of methacrylic acid with a free carboxyl groups of the copolymer based on methacrylic acid and methyl methacrylate with free carboxyl groups of the copolymer on the basis of dimethylaminoethylacrylate and methacrylate copolymer based on methyl acrylate and methyl methacrylate of chlorotrimethylsilane. Interestingly, in the US 5648399 in polymer combination added affecting the release of the active substance reagents from the group of cross stitched reagents, polysaccharides, lipids, polyhydroxyalkane, polycarboxylic acids, divalent cations, citric acid, sodium citrate, docodonta sodium, protein, monooleate of polyoxyethylenesorbitan and amino acids.

Bayston and Grove made an interesting proposal for obtaining medical products (R. Bayston, N. J. Grove: Antimicrobial device and method. 17.04.1990, US 4917686). When this substance with antibiotic action was dissolved in a suitable organic solvent. This solution was left to act on the polymer surface in order to modify. Due to the solvent polymesoda for antimicrobial impregnation of catheters and other medical implants, wherein the antimicrobial active substance dissolved in an organic solvent (R. Darouche, I. Raad.: Anti-microbial impregnated catheters and other medical implants and method of impregnation of catheters and other medical implants antimicrobial agent. 29.04.1997, US 5624704). This solution was left to interact on the treated surface, with the active substance into the material and deposited there.

Alternative still described systems is the method described by Lee, to cover the surfaces of cationic antibiotics (C. S. Lee: Coating medical devices cationic antibiotics 23.01.1990, US 4895566). When the specified method is first applied negatively charged heparin layer on the coated surface and then after attaching the applied cationic antibiotic. A similar solution is proposed Greco and others, in which the first to cover the exposed surface with a solution of anionic surfactant (R. S. Greco, R. A. Harvey, S. Z. Trooskin: Associated with medication prosthesis and method of its production. 07.11.1989, US 4879135). While anionic molecules adsorbed on the surface. Then the cationic active substances, such as gentamicin, are bound electrostatically. the poverhnosti very limited and the strength of the coatings should be considered critically.

The task of the invention is to develop a flexible combination antibiotic/antibiotics polymer, which in physiological conditions provides a continuous release of antibiotics for a period of time from several days to several weeks and can be used in medicine and veterinary medicine. The specified combination antibiotic/antibiotics polymer should be suitable for application with a lasting grip on the surface of the medical synthetic and metal implants. In particular, it is important that the coating is flexible and elastic and does not contain toxic components. Next, a flexible combination antibiotic/antibiotics polymer should be applicable for the manufacture of fibers, films and molded articles.

The invention is based on the surprising fact that a homogeneous polymer blend comprising one or more hydrophobic polymers from the group of polyesters, methacrylic acid, polyesters of acrylic acid, copolymers of esters of methacrylic acid and esters of acrylic acid and one or more hydrophilic polymers from the group of polyethers, in which the suspended one or more slightly soluble in water Antibes is stable composites who in the aquatic environment are slow release of antibiotics for several days. Further explanation suggests the course of the following processes. After making a composite material in the aquatic environment hydrophilic simple polyester is dissolved and goes into solution, while the hydrophobic, water-insoluble polymer remains. There microporous interconnected voids in the remaining hydrophobic polymeric matrix. This means education, first under the action of water or physiological environment in situ interconnected microporous voids. In the specified remaining hydrophobic polymer matrix physically included slightly soluble particles of antibiotics. Thanks educated voids aqueous medium after its occurrence can reach slightly soluble in water antibiotics. Thus, the release of the antibiotic from the beginning during or after washout simple polyester.

These hydrophilic polymers are obvious from the point of view of toxicology and some of their representatives are described in the European Pharmacopoeia. A particular advantage of this combination antibiotic/antibiotics with polymers is that antibiotics, speciesrich and mechanical effects, for example from abrasion. For the first time due to the formation of in situ interconnected microporous voids combination antibiotic/antibiotics polymers proposed for the release of antibiotics. Thanks to the use of slightly soluble in water antibiotics they only slowly excreted from the interconnected voids. In this surprisingly shown that the proportion of hydrophilic polyether in a homogeneous polymer mixture can affect the rate of release of antibiotic.

The objective of the invention is solved in that in a homogeneous polymer blend comprising one or more hydrophobic polymers from the group of polyesters, methacrylic acid, polyesters of acrylic acid and copolymers of esters of methacrylic acid and esters of acrylic acid and one or more hydrophilic polymers from the group of polyethers, suspended one or more slightly soluble in water antibiotics of the aminoglycoside group, lincosamide, tetracycline and quinolone antibiotics, if necessary, easily soluble in water, the antibiotic of the aminoglycoside group, lincosamide,-lactamase and tetracycline antibiotics and, if necessary, one or more organizations which has in practice especially preferred.

According to the invention, the composite is formed from a fluid suspension, which consists of a homogeneous mixture of propane-2-it and/or butane-2-it, one or more hydrophobic polymers from the group of polyesters, methacrylic acid, polyesters of acrylic acid and copolymers of esters of methacrylic acid and esters of acrylic acid and one or more hydrophilic polymers from the group of polyethers, in which the suspended one or more slightly soluble in water antibiotics of the aminoglycoside group, lincosamide, tetracycline and quinolone antibiotics, if necessary, easily soluble in water, the antibiotic of the aminoglycoside group, lincosamide,-lactamase and tetracycline antibiotics and, if necessary, one or more organic auxiliary substances by evaporation of propane-2-it and/or butane-2-it.

In addition, according to the invention, the composite formed from the melt, which consists of one or more hydrophobic polymers from the group of polyesters, methacrylic acid, polyesters of acrylic acid, copolymers of esters of methacrylic acid and esters of acrylic acid and one or more hydrophilic polymers from the group of polyethers, the cat is Mednykh, tetracycline and quinolone antibiotics, if necessary, easily soluble in water, the antibiotic of the aminoglycoside group, lincosamide and tetracycline antibiotics and, if necessary, one or more organic auxiliary substances.

Further according to the invention the content of the hydrophilic polymer in a homogeneous polymer mixture is from 0.1 to 60 mass%.

According to the invention as a simple polyester is preferable to use polyethylene glycol with an average molecular weight in the range from 120 to 35000 g-mol-1.

In addition, according to the invention as a simple polyester preferably use polypropylenglycol with an average molecular weight in the range from 200 to 35000 g-mol-1.

According to the invention as a simple polyester is particularly preferred polyethylene glycol with an average molecular weight in the range from 200 to 600 g-mol-1.

According to the invention as preferred hydrophobic polymers poly (methyl methacrylate), polimetilmetakrilat, polipropilenglicol, poly(n-butyl)methacrylate, poly(n-hexyl)methacrylate, polycyclohexylene, polymethylacrylate, politicalit, polipropilen is.

Also according to the invention as preferred hydrophobic polymers copolymers and terpolymer with an average molecular weight of 20000 to 1000000 g-mol-1that derived from methyl acrylate, ethyl acrylate, propylacetate, n-hexylaniline, cyclohexylacetate, methyl methacrylate, ethyl methacrylate, prophylatically, butyl methacrylate, n-exilicauda and cyclohexylmethyl.

According to the invention as an organic auxiliary substances preferred sulfonamides, and/or anti-inflammatory agents, and/or anesthetic substance, and/or vancomycin.

According to the invention a fluid suspension by moulding with the evaporation of propane-2-it and/or butane-2-it forms the composites in the form of threads.

According to the invention a fluid suspension by casting with the evaporation of propane-2-it and/or butane-2-it forms compounds in the form of films.

According to the invention a fluid suspension by spraying with the evaporation of propane-2-it and/or butane-2-it forms the composites in the form of powders and granulates.

According to the invention the composite material by pressing, extrusion and rolling molded into molded articles and films.

According to the invention coated polymer composite of TC are used as medical implants.

According to the invention catheters, tracheal cannulas and tubes for vnutriarterialnah power coated composite.

According to the invention suitable for implantation of the metal plate, a metal needle, a metal screws covered with composite.

Further according to the invention, the composite is applicable for bonding applicable in medicine, plastics, polymer films, polymer filaments, metal plates and metal tubes.

According to the invention, the composite is used as a binder to obtain antibiotic molded from polymer granules, polymer powders, rezorbiruetsa glass powders, nerenormiruemye glass powder and silica powder.

According to the invention a fluid suspension deposited on the surface of the polymers and/or metals by dipping, spraying, coating, kravanja and rolling and composite in the form of a coating formed by vaporizing propane-2-it and/or butane-2-it.

According to the invention, the composite is applied as a coating on applicable in medicine, polymer fiber, plastic film, plastic tube, plastic bags and plastic bottles.

According to the invention, the composite is applied in kachestvenaia in the form of nets, which consist of polymer and/or metal.

Further according to the invention the composite as a coating deposited on the molded articles, films and threads of polyester methacrylic acid, polyester of acrylic acid, copolymer of esters of methacrylic acid and esters of acrylic acid, polyvinyl chloride, polyvinylidenechloride, silicone, polystyrene and polycarbonate.

According to the invention, the composite is used as a binder for the manufacture of antibiotic layered materials.

Further according to the invention the composite by sintering applied as a coating on the surface of the metal and/or polymeric substances.

The object of the invention is further illustrated by examples.

Example 1

Preparing a solution consisting of 1.5 g of polymethyl methacrylate, 120 mg of polyethylene glycol 600 and 5 ml of acetone. In this suspended solution of 300 mg pesticidecontaminated gentamicin in the form of fine powder and 300 mg of gentamicin sulfate. The resulting suspension was poured on a glass plate, the acetone was evaporated. It was formed of translucent flexible film, which can be separated from the glass plate.

Example 2

Preparing a solution consisting of 1.5 g of primetime the sulfonate powder in the form of fine powder and 300 mg of gentamicin sulfate. In the resulting slurry was dipped a piece of PVC tube length of 3 cm (tube diameter 4 mm). Then covered with a PVC tube was allowed to dry at room temperature. Got elastic procesamiento coating on the PVC tube.

Example 3

In the melt (150C) 2 g of a copolymer of methacrylic acid and of methyl acrylate and 200 mg of polyethylene glycol 600 was introduced and uniformly distributed 200 mg pentakisdodecilsulfat gentamicin in the form of fine powder. After cooling, received milky-turbid solid composite.

Example 4

Preparing a solution consisting of 3.0 g of polymethyl methacrylate, 120 mg of polyethylene glycol 600 and 5 ml of methyl ethyl ketone. In this suspended solution of 406 mg of clindamycine. In the resulting slurry was dipped a piece of PVC tube length of 3 cm (tube diameter 4 mm). Then the PVC tube with the coating was allowed to dry at room temperature. Got elastic procesamiento coating on the PVC tube.

Example 5

Preparing a solution consisting of 3.0 g of polymethyl methacrylate, 120 mg of polyethylene glycol 600 and 5 ml of methyl ethyl ketone. In this suspended solution of 443 mg amatr tube 4 mm). Then the PVC tube with the coating was allowed to dry at room temperature. Got elastic procesamiento coating on the PVC tube.

Example 6

Preparing a solution consisting of 3.0 g of polymethyl methacrylate, 120 mg of polyethylene glycol 600 and 5 ml of methyl ethyl ketone. In this suspended solution of 376 mg of chlorhexidine. In the resulting slurry was dipped a piece of PVC tube length of 3 cm (tube diameter 4 mm). Then the PVC tube with the coating was allowed to dry at room temperature. Got elastic procesamiento coating on the PVC tube.

To confirm prolonged action proposed according to the invention combinations investigated the release of drug samples obtained according to examples 4, 5 and 6.

Samples in the form of a tube with the coating obtained according to examples 4, 5 and 6, made each in 20 ml of saline solution and kept in this solution at a temperature of 37C for 6 days. Sampling was carried out daily. After every sampling volume of the medium was reduced by adding fresh medium. Patvirtinamos microorganism Bacillus subtilis ATCC 6633. The diameter of zone of inhibition was measured by ordinary scanner. The results are presented in the table below.

Claims

1. Combination antibiotic/antibiotics polymer, characterized in that a homogeneous polymer mixture, which consists of one or more hydrophobic polymers from the group of polyesters, methacrylic acid, polyesters of acrylic acid and copolymers of esters of methacrylic acid and esters of acrylic acid and one or more hydrophilic polymers from the group of polyethers, suspended one or more slightly soluble in water antibiotics of the aminoglycoside group, lincosamide, tetracycline and quinolone antibiotics, if necessary, readily water-soluble antibiotic of the aminoglycoside group, lincosamide,-lactamase and tetracycline antibiotics and, if necessary, one or more organic pharmaceutical auxiliary substances, the content of the hydrophilic polymer in a homogeneous polymer mixture is from 0.1 to 60 wt.%, the suspension forms a composite.

2. Combination antibiotic/antibiotics polymer under item 1, characterized in that h is one or more hydrophobic polymers from the group of polyesters, methacrylic acid, polyesters of acrylic acid and copolymers of esters of methacrylic acid and esters of acrylic acid and one or more hydrophilic polymers from the group of polyethers, in which the suspended one or more slightly soluble in water antibiotics of the aminoglycoside group, lincosamide, tetracycline and quinolone antibiotics, if necessary, readily water-soluble antibiotic of the aminoglycoside group, lincosamide,-lactamase and tetracycline antibiotics and, if necessary, one or more organic medicinal excipients by vaporizing propane-2-it and/or butane-2-it.

3. Combination antibiotic/antibiotics polymer under item 1, characterized in that the composite formed from the melt, which consists of one or more hydrophobic polymers from the group of polyesters, methacrylic acid, polyesters of acrylic acid and copolymers of esters of methacrylic acid and esters of acrylic acid and one or more hydrophilic polymers from the group of polyethers, in which the suspended one or more slightly soluble in water antibiotics of the aminoglycoside group, lincosamide, tetracycline and quinolone, Antibac and tetracycline antibiotics and, if necessary, one or more organic medicinal excipients.

4. Combination antibiotic/antibiotics polymer according to one of paragraphs.1-3, characterized in that as a simple it contains a polyester glycol with an average molecular weight in the range from 120 to 35000 g-mol-1.

5. Combination antibiotic/antibiotics polymer according to one of paragraphs.1-3, characterized in that as a simple polyester it contains polypropylenglycol with an average molecular weight in the range from 200 to 35000 g-mol-1.

6. Combination antibiotic/antibiotics polymer according to one of paragraphs.1-4, characterized in that as a simple it contains a polyester glycol with an average molecular weight in the range from 120 to 600 g-mol-1.

7. Combination antibiotic/antibiotics polymer according to one of paragraphs.1-6, characterized in that the hydrophobic polymer it contains polymethylmethacrylate, polimetilmetakrilat, polipropilenglicol, poly(n-butyl)methacrylate, poly(n-hexyl)methacrylate, polycyclohexylene, polymethylacrylate, politicalit, polipropilene, polymethylacrylate and polycyclohexylene with an average molecular weight of 20000 to 1000000 g-mol-1.

8. Combination antibiotic/antibiotics polymer on Adnana molecular weight of 20000 to 1000000 g-mol-1that derived from methyl acrylate, ethyl acrylate, propylacetate, n-hexylaniline, cyclohexylacetate, methyl methacrylate, ethyl methacrylate, prophylatically, butyl methacrylate, n-exilicauda and cyclohexylmethyl.

9. Combination antibiotic/antibiotics polymer according to one of paragraphs.1-6, characterized in that as organic pharmaceutical auxiliary substances it contains sulfonamides, and/or anti-inflammatory agents, and/or anesthetic substance.

10. Combination antibiotic/antibiotics polymer in one of the p. 2 or 4-9, wherein the fluid suspension in the process of formation during the evaporation of propane-2-it and/or butane-2-it forms a composite in the form of threads.

11. Combination antibiotic/antibiotics polymer in one of the p. 2 or 4-9, wherein the fluid suspension in the casting process during the evaporation of propane-2-it and/or butane-2-it forms the composite films.

12. Combination antibiotic/antibiotics polymer in one of the p. 2 or 4-9, wherein the fluid suspension in the process of spraying during the evaporation of propane-2-it and/or butane-2-it forms a composite in the form of powders and granulates.

13. Combination antibiotic/antibiotics with PoE formed into molded articles and films.

14. Combination antibiotic/antibiotics polymer according to one of paragraphs.1-13, characterized in that the composite is deposited on a polymer tube, polymer filaments, and polymer products in the form of balls, the polymer product in the form of a cylinder and the polymer product in the form of nets, suitable as medical implants.

15. Combination antibiotic/antibiotics polymer according to one of paragraphs.1-13, characterized in that the composite is applied to the catheters, tracheal cannulas and tubes for vnutripechenerngo power.

16. Combination antibiotic/antibiotics polymer according to one of paragraphs.1-13, characterized in that the composite deposited on suitable for implantation of a metal plate, a metal needle, a metal screws.

17. Combination antibiotic/antibiotics polymer according to one of paragraphs.1-9, characterized in that the composite is suitable for bonding suitable for medical use polymer molding, polymer films, polymer filaments, metal plates and metal tubes.

18. Combination antibiotic/antibiotics polymer according to one of paragraphs.1-9, characterized in that the composite is suitable as a binder for production of antibiotic molded from powder and quartz powder.

19. Combination antibiotic/antibiotics polymer according to one of paragraphs.1-9, characterized in that the composite is suitable as a binder for production of antibiotic layered products.

20. Combination antibiotic/antibiotics polymer in one of the p. 2 or 4-9, characterized in that it is in the form of a fluid slurry applied by dipping, spraying, brush application, kravanja and rolling on the surface of the polymers and/or metals and by evaporation of propane-2-it and/or butane-2-it is formed of a composite in the form of a coating.

21. Combination antibiotic/antibiotics polymer according to one of paragraphs.1-9, characterized in that it is in the form of a composite is applied as a coating on applicable in medicine, polymer fiber, plastic film, plastic tube, plastic bags and plastic bottles.

22. Combination antibiotic/antibiotics polymer according to one of paragraphs.1-9, characterized in that it is in the form of a composite is applied as a coating on a molded product in the form of balls, molded products in the form of a cylinder and a molded product in the form of a grid consisting of a polymer and/or metal.

23. Combination antibiotic/antibiotics polymer according to one of paragraphs.1-9, characterized in that it is in the form to the s, polyester acrylic acid, copolymer of methacrylic acid and of acrylic ester, polyvinyl chloride, polyvinylidene-chloride, silicone, polystyrene and polycarbonate.

24. Combination antibiotic/antibiotics polymer in one of the p. 1 or 3, characterized in that it is in the form of a composite by sintering applied as a coating on the surface of metals and/or plastics.

 

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