EP2342248A1

EP2342248A1 - Process for preparation of medical grade polyurethane composites containing antibacterial zeolite

Info

Publication number: EP2342248A1
Application number: EP08876341A
Authority: EP
Inventors: Nesrin Hasirci; Nurcan Bac; Kubra Kamisoglu; Burcu Akata Kurc; Eda Ayse Aksoy
Original assignee: Individual
Current assignee: Individual
Priority date: 2008-09-26
Filing date: 2008-09-26
Publication date: 2011-07-13
Also published as: WO2010036214A1

Abstract

This invention is related to the preparation processes and the products of polymeric composites containing antibacterial properties. The composites were prepared from the medical grade polyurethanes and silver ion containing zeolites which the synthesis procedures of both are also included in this invention. Zeolite crystals were prepared in various forms as micro and nano particules and at different SiO2/Al2O3 ratios. Antibacterial properties were included with addition of silver ions into zeolite particules. Medical grade polyurethanes were synthesized from their components in the presence of no other additives in various forms as films sponges or fibers. Composites were formed with combination of these two components. The prepared antibacterial composite materials can be applied in textiles, paint industry, coating materials for metals ceramics or wood, public toilets, keyboards, paper industry, household hygene items, cosmetics, hospital beds and floors, etc.

Description

PROCESSES FOR PREPARATION OF MEDICAL GRADE POLYURETHANE COMPOSITES CONTAINING ANTIBACTERIAL ZEOLITE

FIELD OF INVENTION

This invention is related to production of antibacterial polimers for use in medical and industrial applications. Particularly this invention is about preparation methods for biomedical grade polyurethane based composites, in a variety of forms such as films, fibers and foams containing ionic silver impregnated zeolites with low or high SiO₂/Al2θ₃ ratios.

It is believed that these processed will increase the range of current antibacterial products. Such composites can be used in a wide variety of applications as follows: textiles (upholstery, or clothing fabrics, socks), paint industry ( automotive, marine and household paints) , coating material for metals, ceramics or wood, or coatings for items used in public places, such as escalators, shopping car holders, elevator buttons, steering wheels or stick shifts in cars, keyboards, paper industry (magazines, newspapers) household hygene items (detergents, soaps, shampoo), cosmetics (moisturizer creams), hospital floors, beds and stretchers. Depending on the chemistry of their recipies, the composites prepared may be water soluble or resistant. Water resistant composites are mechanically strong, relatively cheaper and possess increased antibacterial properties when compared to composites containing metallic silver in their composition.

PRIOR ART ABOUT THE INVENTION

With the increased daily use of various products it is desired that these products have certain properties. Therefore, there is a continued interest in developing new materials with tailored mechanical, thermal and radiative properties such that they find wide areas of use. Various materials that are produced for manual handling (keyboards, door handles, credit cards, paper, banknotes, etc.) are desired to have properties that prevent bacterial infections, or those that are used in medical applications need to be antibacterial. Synthetic and natural materials (metals ceramics and polymers) has been used extensively with increasing magnitude in medical applications. Synthetic polymers are used in a variety of biomedical devices, as implants, tissue constructs, fillers, dialysis equipment, contact lenses, artificial veins, catheters, and drug carrier systems. These materials are named as biomaterilas. Biomaterials when used as implants, or when used externally in contact with bodily fluids (in the eye, mouth or in blood) should have properties that are systematically and pharmalogically inert. Polyurethanes (PU) are polymeric biomaterials that are widely used in the biomedical field due to their mechanical properties and their perfect compatibility with blood and tissue as well as the fact that they can be easily modified for certain applications. Besides their wide use in industry, they polyurethanes also find wide use in the medical field in a variety of applications such as artificial veins, catheters, artificial heart valves and parts, stent coatings, and skin grafts. Since polyurethanes can be synthesized in different chemical compositions, they cam be tailored to have desired physical an mechanical properties. They can be prepared as soft elastomeric films, as well as hard and strong parts. Due to these properties they are used as coatings, sponges, fibers and resins in industry. Polyurethanes are synthesized through poiycondensation reactions of isocyanates and polyhydroxy compounds.

O O

U J] Equation 1

HO-R₁-OH H- OCN-R₂-NCO → OCN-R₂-I-NH-C-O-R₁-O-C-NH-R₂I_n-NCO

Poliol Diizosiyanat

Polyurethane chain

15

The most widely used isocyanates in polyurethane synthesis are toluene diisocyanate (TDI), diphenyl methylene diisocyanate (MDl), p-phenylene diisocyanate (PDI), and naphthalene diisocyanate (NDI). The widely used polyhydroxy compounds are polyether and polyester glycols containing hydroxy groups with a molecular weight of 400-5000 Da. Isocyanates form the hard units of the PU structure, while glycol cahins in the form of polyols form the soft units. When both units co-exist in the micro phase separations, the structure becomes elastomeric.

There has been some work in the literature on antibacterial PU films and foams. These studies involves some additives or catalysts during the synthesis step. The additives used may have toxic effects, so the use of such materials in health related applications are limited. More over some products in literature report the addition of silver ions to commercially available zeolites in order to achieve antibacterial activity. However, in these product it is reported that the antibacterial activity is achieved then the SiO₂/AI₂O₃ ration is at most 14. (Hagiwara, Z, Hoshino, S., Ishino, H., Noara, S., Tagawa, K., Yamanaka, K., Polymer article having an antibacterial property containing zeolite particles therein and the processes for producing the same, U.S. Patent, No: 4,775,585, 1988). Zeolites are known to be considered mainly in 3 groups according to their silica/alumina ratios. These are zeolites with low (i.e.,zeolite A and X), medium (i.e., zeolite X and mordenite), and high (i.e.: zeolite Beta and ZSM-5) SiO₂ZAI₂O₃ ratios. To date all antibacterial materials with zeolite and PU have been with zeolites having low or medium SiO₂ZAI₂O₃ ratios. Antibacterial zeolite with a high SiO₂ZAI₂O₃ ratio has not been studied yet, moreover there are reports that they can not be made antibacterial. It is significant to produce an antibacterial zeolite with a high SiO₂ZAI₂O₃ ratio and to produce a composite that is more compatible with the polymer since the hydrophilicZhydrophobic property of the zeolite can be controlled with the SiO₂ZAI₂O₃ and the mechanical strength of the material is relatively improved and importance of the composite in various applications is enhanced.

AIMS FOR DEVELOPMENT OF THE INVENTION

The aims of developing a process to produce medical grade PU films, fibers and sponges containing antibacterial zeolites and their preparation methods include :

• Producing antibacterial zeolite Beta with a high SiO₂ZAI₂O₃ ratio.

• Assessment of high SiO₂/AI₂O₃ ratio zeolite Beta to have at least or even more antibacterial activity than zeolites with low or medium SiO₂/AI₂O₃ ratios.

• Synthesis of homogenous zeolites as micro andZor nanosized crystals and giving them the antibacterial property

• Production of biomedical grade PU films, fibers or foams at various elastomeric properties with no catalysts or additives. • incorporation of zeolites into biomedical grade PU with no binder resulting in a new composite material.

• Production of a stronger composite material than pure PU.

• Production of a composite material whose hydrophilicZhydrophobic property can be controlled and adjusted. • Production of an antibacterial composite that is compatible with polymers and can be ble.nded into the polymers homogeneously with no binders.

DESCRIPTION OF THE FIGURES Figure 1. SEM (Scanning Electron Microscope) photomicrographs of silver ion loaded zeolite Beta (a) and Zeolite A (b).

Figure 2. SEM photomicrographs of silver ion loaded nano sized Zeolite A crystals. Figure 3. SEM photomicrographs of Polyurethane sponge Figure 4. Chemical structure of Polyurethane synthesized from TDI and polypropylene.

Figure 5. FTIR (Fourier Transform Infrared) spectra of PU synthesized from TDI and polypropylene ethylene glycol.

Figure 6. . SEM photomicrographs composites prepared with silver ion loaded Zeolite A (a,b,c) and zeolite Beta (d,e,f) Figure 7. Effect of various zeolites on aqueous E. coli before (b, c, d) and after (e, f, g) loading with silver ion.

Figure 8. Composite materials in fiber (a, a'), film (b, b^!), and sponge (c, d, c', d') forms, and their effect on E. coli.

DESCRIPTION OF THE INVENTION

This invention involves preparation of biomedical grade PU with various elastomeric properties by reacting toluene diisocyanide (TDI) and polypropylene ethylene diisocyanide (polyol) without any additives, and making these materials antibacterial with the incorporation of zeolites. Since no additional catalyst or chain modifier compounds are used in PU synthesis, the toxic effects of such ingredients are eliminated. This product is of biomedical grade and can be tailored to have desired mechanical properties, so it is a strong candidate for the development of biomedical devices . Zeolite crystal containing silver ions are incorporated into the polyurethane structure so the composite becomes antibacterial.

One of the most widely used forms of polyurethanes is the sponge form. This structure is obtained by adding water into the viscous polyurethane prepolymer. Only water is used in this step and no other chemical is present, and this is significant in the sense that biomedical grade purity of PU is not affected. The formation of the sponge-like structure, at first the isocyanide groups reacts with water to give an unstable carbamic acid (Equation 2). Carbamic acid then decomposes into an amine and gaseous carbon dioxide which causes the spongy structure (Equation 3). The amine molecules react with isocyanates and urea groups form in the chain (Equation 4), This process forms the spongy polyurethane-polyurea foam. In this invention PU is also prepared in a spongy form and silver ion loaded zeolites are incorporated into this structure forming an antibacterial composite.

H O R-N=C=O + H_aO^→ R-N-C O-H (Equation 2)

H O R-N-C-O-H — R-NH_a+ CO_a (Equation 3)

H O H R NH₂ ⁺ Ri-N=C=O - R-N- C-N-Ri (Equation 4)

There are various reports in literature for making polyurethanes antibacterial.

Examples are, by addition of various chemicals, [i.e., N-(fluorodichloromethylthio)- phthalimide, 2-benzimidazole carbamic acid lower alkylester and/or 2-(4-thiazolyl)- benzimidazole (USPTO Patent Application #: 20050245627 - Patent Class: 521099000)] by addition of organic dyes (methylene blue, toluidine blue, methylene violet, azure A, azure B, azure C, brilliant cresol blue, thionin, methylene green, bromcresol green, gentian violet, acridine orange, brilliant green, acridine yellow, quinacrine, trypan blue, trypan red (European Patent No:1490140 Medical Devices Exhibiting Antibacterial Properties), or through coating with or adding particles of metallic silver (Schierholz et al., J. of Hosp. Inf., 40, 257- 262, 1998; Wang et al., Surf. Coat. Technol. 201, 6893-6896, 2007; Gray et al., Biomaterials, 24, 2759-2765, 2003; Jain and Pradeep, Biotechnol. and Bioeng., 90, No. 1, 2005; Radheshkumar and Mϋnstedt, React. Fund Polym., Polymers 66, 780-788, 2006; Radheshkumar and Mϋnstedt, Biomaterials, 26, 2081-2088, 2005; Bechert et al., Infection, 27, 24-29, 1999; Chou et al., Polym. Degrad. Stab., 91, 1071-1024, 2006) .

There are various antibacterial heavy metals (Ag, Cu, Zn, Ti, etc.). The most widely used one is silver due to its stable structure, long term effects, and effects on wide spectra of bacteria. Silver can be used in the form of metallic silver (Ag) or in ionic form

(Ag⁺). The strong effect of metallic silver on harmful microorganisms has been known since early ages. Powdered silver metal can be added into polymers to produce antibacterial materials. However, compatibility problems may exist with metal-polymer composites containing metallic silver due to differences in specific gravity and mechanical properties of these materials. Moreover, when metallic silver is added manufacturing cost of such composite materials may be prohibitively high. Therefore, instead of metallic silver, incorporation of silver ions are preferred in many applications. Besides, it is reported that the antibacteria; activity of silver ions is more effective than its metal form (Schierholz et al., J. of Hosp. Inf., 40, 257-262, 1998). Thus an antibacterial material should be prepared such that it should preferably contain silver ions. This invention involves incorporation of silver ion loaded zeolite crystals into PU resulting in an antibacterial composite material. Zeolites, unlike other inorganic compounds, possess a uniform micro/nanoporous structure that are excellent ion exchangers.

Zeolites are homogenous four faced crystalline aluminosilicates composed silica [SiO₄] and alumina [AIO₄]^" groups (or other oxides) linked by shared oxygen atoms. They contain micro or nanoporous channels of uniform size linked in a 2-dimenisonal or 3- dimensional network, and this structure enables them to have very large surface areas per unit mass. The size and shape of zeolitic pores as well as the cage-like structure of the crystal determines the property of the zeolite. As the relative amount of alumina tetrahedra is increased the structure becomes more negatively charged. This results in increasing the amount of positively charged metal cations in the pores that would balance the crystal. Therefore, adjusting the SiO₂/AI₂O₃ ratio in the zeolite results in tailoring quantity of adsorbable cations in the structure. This gives a multitude of functional and structural properties to zeolites. Zeolites are classified according to their SiO₂/AI₂O₃ ratios. In general they can have low (zeolite A and X), medium (X, mordenite), or high (Beta, ZSM-5) silica/alumina ratios. This property of zeolites controls their capacity to have silver ions in the structure, and their compatibility with the organic material while making the composite, as well as their antibacterial efficacy. Thus, the resulting composite can be tailored to have the antibacterial and mechanical properties desired for the specific application. The antibacterial efficacy of zeolites is significant for sterilization purposes. Antibacterial zeolite powders can be added into the microstructure of various materials that are handled daily ( i.e, toilet seats, paper money, keyboards, etc.), or into household cleaners, fabrics, and biomedical devices to prevent buildup of bacteria on these materials. This invention involves synthesis of two different types of antibacterial zeolites with different SiO₂/AI₂O₃ ratios, preparation of the PU prepolymers in various physical forms, and combining these two in a composite structure. The resulting composite material resembles the polymer in thermal properties, but shows superior mechanical performance than the pure polymer. Moreover, adjusting the parameters in preparation of both the polymer and zeolite (i.e., chemical composition, crystal structure, pore size, etc) the properties of the resulting product is controlled in the desired direction. This was achieved by controlling both the polymer and zeolite compositions and adjusting the types of metals in the structure, and/or tailoring the zeolite pore size and crystal structure. This invention involves the ability of tailoring the zeolite synthesis and its crystaline and chemical properties, optimizing the synthesis parameters (temperature, time), and their compatibility with polymers, resulting in an improved poylymer-zeolite composite. Thus, resulting composites are mechanically stronger than polyurethanes currently used. Zeolites containing silver ions are incorporated into a biocompatible polymer for the first time, and the resulting composite material can have wide potential applications in many areas, such as medical devices, paper, textile, plastics, and detergents.

In literature there are report of antibacterial zeolite composites with silver, and with low or medium SiO₂ZAI₂Oa ratios such as zeolite A, X, Y and mordenite. (Maeda and Nose,

Artificial Organs 23, 2, 129-130, 1999; lnoue et a\., J. of Inorg. Biochem., 92, 1, 37-42, 2002; U.S.

Patent, No: 4, 775,585; European Patent No: 1869980; European Patent Office, WO02089766; L/.S. Patent Application 20060121078; U. S. Patent No: 4, 937,273).

However, this invention for the first time describes preparation of an antibacterial zeolite ( Zeolite Beta) with a high SiO₂ZAI₂O₃ ratio, and a large pore size, and the resulting product is incorporated into biomedical grade polyurethane for the first time, resulting in a new composite material. Moreover, this material is more compatible with the polymer, and the resulting composite is stronger than pure polyurethane. Among other zeolites, a property of Zeolite Beta is its high SiO₂/AI₂O₃ ratio, and for this reason it is highly hydrophobic than zeolites with low or medium SiO₂/AI₂O₃ ratios. Therefore Zeolite Beta is more compatible with polymer, and can have a homogeneous distribution in the composite. This work proves that zeolites with both high and low SiO₂/AI₂O₃ ratios can be synthesized, and antibacterial property can be added, and the structural properties can be controlled along with the hydrophilic/hydrophobic properties while preparing compatible organic-inorganic composites.

Zeolites are synthesized as micron and nanosized crystals and they are made antibacterial by loading with silver ions. In most cases materials are made antibacterial by adding metallic silver nanoparticles into the structure. However the antibacterial effect of metallic silver is less than ionic silver. Since micro and nanosized zeolite crystals are loaded with silver ions this will minimize the amount of silver used and the resulting product is much less costly. In literature it is reported that chitosan is made antibacterial by adding silver nanoparticles and zeolite A loaded with silver ions, and about 10 % less silver was needed in case of using zeolite A instead of silver nanoparticles. Moreover composites prepared with silver nanoparticles were mechanically weaker, since these were not distributed homogeneously in the structure. (Preparation and Characterization of Chitosan-Based Nanocomposite Films with Antimicrobial Activity, Jong-Whan Rhim, Seok-ln Hong, Hwan-Man Park, and Perry K. W. N., J. Agric. Food Chem., 54 (16), 5814 -5822, 2006).

In this invention mechanical strength of antibacterial composites prepared with addition of silver ion loaded zeolites were found to increase by 70% in comparison to pure PU. Moreover, adding more silver nanoparticles to increase the antibacterial efficacy may have adverse effects due to human health considerations. Instead utilizing zeolites nanocrystals with a high SiO₂ZAI₂O₃ ratio and making these by ion exchange with silver ions, makes the process more cost effective and results in a product with no adverse health effects. Zeolites synthesized as nanoparticles have a much larger surface area than the micron sized particles, hence the atom ratio on the surface and the intraparticle diffusion path is increased. This makes the interaction between the polymer and the silver ion loaded zeolite particles much stronger, and the antibacterial effect of the composite lasts longer.

The composites composed of antibacterial zeolite and biomedical grade polyurethane film, fiber and sponges that are described in this invention are prepared by the following processing steps. • Synthesis of polurethane prepolymer,

• Synthesis of zeolite,

• Making zeolites antibacterial.

• Preparation of composites,

• Preparation of composites in the form of sponge.

Step 1 Synthesis of Polyurethane Prepolymer

Biomedical grade polyurethane is synthesized from diisocyanide (DDI) and polyol with no other additives. PU Synthesis is done in a closed reactor under vacuum where a predetermined amount of DDI can be added. After polyol is heated to 70°C-150°C and the reactor is evacuated, DDI is added and polymerization starts and continues 70-150⁰C while the mixture is being stirred. Thus polyurethane prepolymer at a low viscosity is obtained. During the PU synthesis, various amounts of DDI is added into the polyol in order to change the polyol/DDI ratio. The pure polyurethane produced has different mechanical properties depending on its synthesis conditions and the ratios of materials used. If desired, additives to extend the chain length (chemicals containing carbon and hydrogen, or oxygen, nitrogen and sulfur) can be used

PU synthesis involves using various diisocyanides and polyols at different ratios resulting in polymers with different mechanical properties. As diisocyanides (DDI), toluene diisocyanide (TDI), 4-4 diphenyl diisocyanide (MDI), hexamethylene diisocyanide (HDl) are used. As for polyols, polypropylene ethylene glycol (PPEG), polypropylene glycol

(PPG), are used at various molecular weights.

Other diisocyanides (DDI) besides toluene diisocyanide (TDI), 4-4 diphenyl diisocyanide (MDI), hexamethylene diisocyanide (HDI), can be used in polyurethane synthesis, such as naphthalene-1 ,5 diisocyanide (NDI), xylene diisocyanide (XDI), dicyclohexylmethane diisocyanide (PICM), isofurane diisocyanide (IPDI), 4,4'- methyldicyclohexane diisocyanide (Hi₂MDI), 1,4-cyclohexane diisocyanate (CHDI) can be used. Moreover, instead of polyurethane and polyol other polymeric materials such as other carbon and hydrogen containing monomers and polymers, as well as the ones containing oxygen, nitrogen, sulfur, fluorine and chlorine containing monomers and polymers can be used. The temperature for synthesis reaction can vary in the range 50 to 200⁰C.

In this study, unlike other synthesis work with antibacterial zeolites, no additives or solvents are used in the synthesis, resulting in a biomedical grade product. Thus no small molecular weight toxic compounds that can leak out of the polymer can exist. Biomedical grade sponge-like polyurethane material is synthesized for the first time with this invention. Therefore, polyurethanes synthesized by this method can find various uses in medical applications or in health sciences.

Step 2 Synthesis of Zeolites

Zeolite Beta with a high SiCVAI₂O₃ ratio is synthesized hydrothermally from gel solutions. For the preparation of the gels, colloidal silica as a silica source (sodium silicate, sodium metasilicate pentahydrate, sodium metasilicate nonahydrate, fumed silica, precipitated silica, tetramethylorthosilicate, and tetraethylorthosilicate can be used as alternatives); sodium aluminate as an aluminate source (aluminum metal, aluminum nitrate, aluminum sulfate, aluminum hydroxide, aluminum isopropoxide can be used as alternatives); sodium hydroxide powder as a soda source; and tetraethyl ammonium hydroxide solution is used as the organic structure directing agent. The gel compositions prepared according to 2.2 Na₂O: AI₂O₃: 20 SiO₂: 4.6 (TEA)₂O: 443 H₂O (Akata B., Yilmaz B., Jirapnogphan S. S., Warzywoda J., Sacco, Jr., A, Characterization of zeolite Beta grown in microgravity, Microporous and Mesoporous Materials, 71, 1-9, 2004) molar compositions is mixed thoroughly before putting into the Teflon lined stainless steel autoclaves and are kept at a high temperature of synthesis (150-200⁰C) under the resulting pressurized atmosphere for 8-10 days. The autoclaves were kept statically at 150⁰C in a conventional oven for 8 days. The resulting solid particles were vacuum-filtered, washed with deionized water and dried before storing. The SiO₂/AI₂O₃ ratio of the zeolite Beta synthesis gel composition is set at 20. This ratio is higher than any other ratios of the similar zeolite materials, such as zeolite A and X, as stated in other related studies and patents. Similarly, in order to obtain the micron sized zeolite A particles, sodium mathasilicate pentahydrate as a silica source (colloidal silica, sodium silicate, sodium metasilicate pentahydrate, sodium metasilicate nonahydrate, fumed silica, precipitated silica, tetramethylorthosilicate, and tetraethylorthosilicate can be used as alternatives); sodium aluminate as an aluminate source (aluminum metal, aluminum nitrate, aluminum sulfate, aluminum hydroxide, aluminum isopropoxide can be used as alternatives); sodium hydroxide powder as a soda source; and tetraethyl ammonium hydroxide solution is used

^• as the organic structure directing agent. The gel compositions are prepared according to

3.39 Na₂O: AI₂O₃: 1.77 SiO₂: 1 17 H₂O (Robson, H., Lillerud, K. P., "Verified Syntheses of

Zeolitic Materials", Published on behalf of the Synthesis Commission of the International Zeolite Association, 2nd Revised Edition, 2001) molar compositions and upon keeping the zeolite solution at high temperature, under atmospheric pressure and for 8-10 days. The obtained zeolite crystal sizes are around 1.5-2 μm (Figure 1).

The synthesis of nano sized zeolite A crystals is done under a better controlled environment. For the preparation of the gels, tetraethylorthosilicate as a silica source; aluminum isopropoxide as an aluminate source; sodium hydroxide powder as a mineral source; and tetraethyl ammonium hydroxide solution is used as the organic structure directing agent. The clear gel compositions are prepared according to 0.6 Na₂O: 1.8 AI₂O₃: 11.25 SiO₂: 13.4 (TMA)₂O: 700 H₂O molar compositions. After keeping zeolite solutions at high temperature (80-100⁰C), the synthesized nano-zeolite crystals are obtained after high speed centrifugation, filtration and drying.

Step 3 Preparation of Antibacterial Zeolite Samples

The cation-exchange process is done using AgNO₃ to the synthesized zeolites in

Step 2. Zeolite samples are put into a solution of AgNO₃ and the resulting solution is is stirred in the dark for some time in order to achieve the exchange of ions. The silver loaded zeolite powders are vacuum filtered and dried. The ion exchanged zeolite Beta is calcined afterwards in order to remove the organic structure directing agent, which is not necessary for other types of zeolites. The amount of silver ion 5.5 ± 0.02 for zeolite Beta, and 10.5 ± 0.01 for zeolite A. Figure 1 and 2 are showing the scanning electron electron micrographs of silver loaded zeolit Beta (Figure 1-a) and zeolite A (Figure 1-b). Zeolite Beta is shown for the first time to possess an antibacterial effect, despite the relatively high SiO₂ZAI₂O₃ ratio, in spite of the fact that it exhibits less silver ion with respect ot the other well known antibacterial zeolites types. Furthermore, in the current invention, a nano-sized zeolite sample (< 1 μm) was shown to exhibit antibacterial activity for the first time.

Step 4 The Process for Composite Preparation

Zeolites that were prepared as described in steps 2 and 3 were dried at 80⁰C, sieved (Sieve No. 100) to break up zeolite lumps and added to the freshly prepared viscous prepolymer. Desired amount of zeolite can be added into the mixture. Preferably, depending on the property of the polymer, %0.01-50 weight percent of zeolite is added to the prepolymer. The homogeneous mixture is prepared in the petri dishes after which it is placed in a vacuum oven and cured. At the end of the process, the prepared composites are taken out of the petri dishes, which are made ready for use. According to the present invention, silver ion exchanged zeolites were added into a biomedical grade polyurethane, and this biomedical grade polyurethane composite was shown to possess antibacterial properties. Further, a high SiO2/AI2O3 ratio zeolite Beta was used for composite making purposes for the first time, which shows superior mechanical properties with respect to the pure polyurethane. The same properties were obtained by using nano sized zeolite A instead of zeolite Beta. More specifically, the present invention provides an antibacterial polymer article prepared by adding a high silica zeolite or a nano sized zeolite having antibacterial properties similar, which was prepared without using chemical linkers between the organic-inorganic materials. A great variety of polymers can be used with different variety of high silica and/or nano sized zeolites.

Step 5 Preparation of antibacterial composites in sponge form

Water is added into the viscous composites prepared according to Step 4 to speed up the reaction between the isocyanide groups and water. The swollen material is cured at high temperatures to obtain the composites in sponges forms. The scanning electron microscope image of the obtained composite is shown in Figure 3. In order to obtain the sponge form, it is also possible to pass different gases from the environment and make the polymer swell. If there is no gas flow or water addition in the environment, thin films with smooth and polished like surfaces are obtained. Thus, the composites made by adding zeolites into a biomedical grade polyurethane films and sponges are made in the present invention.

Example 1 Compositions of the Prepared Polyurethane Films

The polyurethane film compositions prepared from different diisocyanate and polyol types with different mole ratios are given in the table below.

Sample Code Mole ratio Mole ratio

Polyol/DDI^a C¹VDDI

PPEG/TDI

TPU2.5T 0.40 -

TPU5T 0.20 -

TPU 1OT 0.10 _

TPU25T 0.04 -

TPU50T 0.02 -

PPG/TDI

TPU1.5T(1)^b1 0.67 -

TPU2T(1) ^b1 0.50 -

TPU2.5T(1) ^b1 0.40 -

TPU3T(1) ^b1 0.33 -

TPU4T(1) ^b1 0.25 -

TPU2T(2) ^b2 0.50 -

TPU3T(2) ^b2 0.33 -

TPU4T(2) ^b2 0.25 -

PPEG/MDI

MPU50M 0.02 -

MPU10M 0.10 -

MPU5M 0.20 -

MPU3M 0.33 -

MPU1.5M 0.66 -

PPEG/HMDI

DPU5D 0.20 -

DPU1.5D 0.67 -

^a DDI = TDI for T samples, DD! = MDI for M samples, DDI = HDI for D samples.

^M PPG is used as a polyol with molecular weight of 1025 g mol^'1 in the sample notation of (1). b² PPG is used as a polyol with molecular weight of 2025 g mol^"1 in the sample notation of (2).

^CC defines the presence of chain extender.

For all other samples, polypropylene ethylene glycol was used as the polyol and no chain extender was used.

Example 2 Chemical Structure Analysis of Synthesized Polyurethane

The chemical formula of polyurethane synthesized from TDI and polypropylene ethylene glycol is shown in Figure 4. The chemical characterization of synthesized polyurethane was done with FTIR spectroscopy. The FTIR spectrum of polyurethane structure synthesized from TDI and polypropylene ethylene glycol is shown in Figure 5.

In FTIR spectra characteristic signals observed for polyurethane are at 3300 cm^"1 and 1726-1705 cm^"1 wavelenghts. All polyurethanes synthesized form diisocyanate and polyol have shown these characteristic FTIR signals. In polyurethane which is synthesized from TDI and polypropylene ethylene glycol and the FTIR spectra is shown, the signal at 3297cm^"1 is the presence of structure hardening hydrogen bonding N-H stretching vibration. The signals at 2968 cm^'1 and 2866 cm^"1 corresponds to C-H bond asymmetric and symmetric stretching in polyurethane structure. A strong signal belonging to C=O unit in polyurethane structure is observed at 1715 cm^"1 wavelenght.

Example 3 Mechanical Properties of the Prepared Polyurethane Films

The mechanical test results showing the values of elastic modulus, ultimate tensile strength and ultimate elongation for all polyurethane films prepared with different compositions are tabulated in table shown below.

Sample code Mole ratio Modulus Ultimate Ultimate

Polyol/DDI^a (MPa) Tensile Elongation

Strength (%)

(MPa)

PPEG/TDI

TPU2.5T 0.40 0.4 2.7 437

TPU5T 0.20 4.2 10.0 177

TPU 1OT 0.10 7.6 29.4 295

TPU25T 0.04 9.4 26.0 266

TPU50T 0.02 9.9 38.5 272

PPG/TDI

TPU1.5T(1)^b1 0.67 3.5 1.9 95

TPU2T(1) ^b1 0.50 4.9 3.1 87

TPU3T(1)^b1 0.33 9.3 4.6 84

TPU4T(1) 0.25 13.1 5.4 71

TPU2T(2) ^b2 0.50 2.8 1.9 105

TPU3T(2) ^b2 0.33 8.6 2.9 96

TPU4T(2) ^b2 0.25 13.6 1.5 33

PPEG/MDI

MPU 10M 0.10 34.5 20.0 21

MPU5M 0.20 21.5 5.6 35

MPU3M 0.33 10.5 3.0 21

MPU1.5M 0.66 3.4 0.9 25

PPEG/HMDI

DPU5D 0.20 6.1 2.4 51

DPU1.5D 0.66 0.6 0.2 31

^a DDI = TDI for T samples, DDI = MDI for M samples, DDI = HDI for D samples. b¹ PPG is used as a polyol with molecular weight of 1025 g mol^"1 in the sample notation of (1). ^b2 PPG is used as a polyol with molecular weight of 2025 g mol^"1 in the sample notation of (2). ⁰C defines the presence of chain extender. For all other samples, polypropylene ethylene glycol was used as the polyol and no chain extender was used.

In polyurethane structures diisocyanates form the hard segments and polyols form the soft segments. Presence of hard segments in the structure increases materials resistance to deformation while soft segments effects the elongation upon tension. In polyurethane structure, when the amount of hard segments increases, ultimate elongation values are expected to decrease because of an increase in crosslinking. An increase in modulus and decrease in ultimate elongation was observed as the TDI content increases for TPU2.5T - TPU10T samples prepared from TDI. It is observed from the table that the use of chain extender increased the mechanical properties in polyurethane synthesis. However, because of the possible toxic effects of chain extenders, for the purpose of making antibacterial polyurethane, chain extenders were not preferred in the current innovation and the desired mechanical properties were arranged by increasing the amount of diisocyanate. For the selected polyol type, as the molecular weight decreases from 2025 PPG to 1025 PPG, elastic modulus increases and elongation of materials decreases. For the polyurethane sample group prepared from HDI and MDI isocyanates, MDI based polyurethanes had shown higher elastic modulus and lower elongation due to the stiffness of MD! aromatic ring. MDl produces stiffer polyurethanes in comparison with TDI. Thus, upon the comparison of MPU10M and TPU10T samples, it was observed that MPU 10M has higher elastic modulus.

Example 4 Zeolite ~ Polymer Composites

The pictures of zeolite polymer composite as described in Step 4 are shown in Figure 6. According to this figure, the zeolite particles in the obtained composites are homogeneously distributed in the polymer matrix. Achieving homogenous distribution in the composite materials is important, since it brings mechanical enhancement into the obtained product. Usually chemical linkers are used to increase the interactions between the inorganic fillers and polymer (D. Q. Vu, W. J. Koros, S. J. Miller, Mixed Matrix Membranes using carbon molecular sieves: I. Preparation and Experimental Results, J. Membr. Sci, 211, 2003, 311; T. W.

Pechar, M. Tsapatsis, E. Marand, R. Davis, Preparation and Characterization of a glassy fluorinated polyamide zeolite mixed matrix membrane, Desalination, 146, 2002, 3; Cao, X.; Lee, L J.; Widya, T.;

Macosko, C. Polyurethane/clay nanocomposites foams: processing, structure and properties; Polymer 2005,

46, 775). However, the additional usage of these chemicals may alter the physical and chemical properties of the product. In the current innovation, a homogeneous dispersion of zeolite particles in the polymer was obtained without the addition of any chemical linker and more durable product was obtained compared to the pure polyurethane. Attaining better compatibility between the zeolite and polymer is possible by controlling the zeolite's hydrophilic/hydrophobic properties in order to make it more similar to that of polymer. For that purpose, it is important to control the SiO2/AI2O3 ratio of the zeolite and to obtain antibacterial activity in a high silica zeolite material. In this product, instead of using polyurethane, any other polymeric material such as any monomers and polymers containing either only carbon and hydrogen in their structure; or the ones containing oxygen, nitrogen, sulphur, florine, and chlorine in addition to carbon and hydrogen can be used.

Example 5 Antibacterial tests - Zeolite powders

The antibacterial properties of zeolite powder samples with silver ion were tested on the most well known pathogenic Escherichia coli bacteria type. For this purpose, Ag⁺- zeolites were placed in the bacterial solutions prepared with deionized water. After waiting for 24 hours, they were taken from these solutions and placed in the feeding medium. The concentration of the solutions were arranged to make them 500 ppm. The antibacterial properties of Ag⁺- zeolites were examined by controlling the bacterial growth on agar plates.

The effect of zeolite powder samples on E. coli in liquid media before and after silver ion loading into the zeolites are shown in Figure 7. Figure 7-a shows the blank solution containing only E. Coli in deionized water, which was used to observe the normal growth of the bacteria on agar plates. Figures 7-b and c show the growth of bacteria on zeolite Beta and zeolite A without any silver ion loading; whereas Figures 7-d and e show the growth of bacteria on zeolite Beta and zeolite A with silver ion loading and thus were induced antibacterial properties. The embedded close-up figures are optical microscopy images of the agar surfaces. These tests clearly show that zeolites with no silver loading had no effect on the growth of E. Coli, while silver loaded zeolites showed antibacterial property even at low concentrations (500 ppm).

Example 6 Antibacterial tests - Composite samples The effect of zeolite films and sponge composites with antibacterial properties on the bacterial growth were examined by disc diffusion test. For that purpose, the composite samples were placed on the agar plates containing bacterial colonies as described in Example 5, and the bacterial growth inhibition zones were observed around the composite samp\es. Figure 8 shows the diffusion test results carried out to examine the antibacterial properties of the composites. Figures 8-a , b, c, and d are showing the diffusion test results of pure polyurethane fiber (a), film (b), sponge (c) and after removal of sponge (d) from the media and their effects on the bacteria. Figure 8-a', b', c' and d' show the same materials prepared as composites with addition of silver ion loaded zeolite Beta and their effects on E. coli medium. Because of the porous structure of the sponge composites their adhesion on the feeding surface is small, and therefore the antibacterial effect is more clearly seen (d¹) after the removal of the material. As seen from the photograph the growth of the bacteria is prevented in the mentioned area. On Figure 8, the composites of polyurethane fiber and films (a,b) obtained with addition of no water and the composites prepared with addition of silver ion containing zeolites (a' and b') are also shown. According to this figure, there were ~ 1-2 mm bacterial growth inhibition zone around the composite samples, whereas no clearance was observed around the pure polyurethane. The reason of the observed thin inhibition zone area is due to the slow diffusion rate of Ag+ ion in the agar medium. The fact that the antibacterial effect was observed in the close environment of the composites is an advantage for biomedical applications, because high silver ion concentrations might be hazardous for human tissues.

Claims

1- The process for production of biomedical grade polyurethaπe composites containing antibacterial zeolites, involves the following processing steps;

• Synthesis of biomedical grade polyurethane prepolymer from diisocyanate (DDI) and polyols with no other additives,

• Zeolite synthesis,

• Making zeolites antibacterial,

• Preparation of composites

• Preparation of antibacterial composites with a spongy structure.

2- As stated in claim 1 the process for preparation of biomedical grade polyurethane composites containing antibacterial zeolites consists of preparation of polyurethanes in medical purity, by mixing polyols that are heated to 70°C-150⁰C in vacuum, with DDI. The polymerization starts and continues at this temperature in vacuum and fluid polyurethane prepolymer is obtained.

3- As stated in claims 1 and 2 the process for preparation of biomedical grade polyurethane composites containing antibacterial zeolites involves addition of various amounts of DDI into the polyol monomer enables changing the Polyol/DDI ratio in the preparation of polyurethane in medical purity. 4- As stated in claims 1 , 2 and 3 the process for preparation of biomedical grade polyurethane composites containing antibacterial zeolites involves using disocyanates (DDI) such as toluene diisocyanate (TDI), 4-4 diphenyl diisocyanate (MDI), and hexamethylene diisocyanate (HDI) during the synthesis of polyurethanes.

5- As stated in claims 1 , 2, 3 and 4, the process for preparation of biomedical grade polyurethane composites containing antibacterial zeolites involves using polypropylene ethylene glycol (PPEG), and polypropylene glycol (PPG) and their various forms at different molecular weights as polyols during the synthesis of polyurethanes.

6- As stated in claims 1 , 2, 3, 4 and 5 the process for preparation of biomedical grade polyurethane composites containing antibacterial zeolites involves using a variety of diisocyanates (DDI) other than toluene diisocyanate (TDI), 4-4 diphenyl diisocyanate (MDI), and hexamethylene diisocyanate (HDI) during the synthesis of polyurethanes. These are: Naphthalene-1 ,5- diisocyanate (NDI), Xylene diisocyanate (XDI), dicyclomethane diisocyanate (PICM), isofurane diisocyanate (IPDI), 4,4'- dicyclohexamethane diisocyanate (H₁₂MDI) or 1 ,4-cyclohexane diisocyanate (CHDI) .

7- As stated in claims 1 , 2, 3, 4, 5 and 6 the process for preparation of biomedical grade polyurethane composites containing antibacterial zeolites involves operating at temperatures between 50 to 200°C during the synthesis of polyurethanes.

8- As stated in claims 1, 2, 3, 4, 5, 6, 7, 8, or 9 the process for preparation of biomedical grade polyurethane composites containing antibacterial zeolites involves use of besides polyurethane and polyol, other polymeric materials such as other carbon and hydrogen containing monomers and polymers, besides carbon and hydrogen the ones containing oxygen, nitrogen, sulfur, and halogen (fluorine, chlorine, bromine, iodine) containing monomers and polymers.

9- As stated in any of the claims above, the process for preparation of biomedical grade polyurethane composites containing antibacterial zeolites involves use of besides polyurethane, other monomeric chemicals and chain extenders with similar compositions containing carbon and hydrogen, as well as oxygen, nitrogen, and sulfur.

10-As stated in any of the claims above, the process for preparation of biomedical grade polyurethane composites containing antibacterial zeolites involves using AgNO₃ solutions for making high SiO₂ZAI₂O₃ ratio zeolite Beta and nanocrystalline zeolit A antibacterial.

11-As stated in any of the claims above, the process for preparation of biomedical grade polyurethane composites containing antibacterial zeolites involves mixing zeolites with silver nitrate solutions for ion exchange followed by separating the silver ion containing zeolite powder from the solution and drying. 12-As stated in any of the claims above, the process for preparation of biomedical grade polyurethane composites containing antibacterial zeolites involves calcining zeolite Beta after ion exchange process and drying steps in order to remove the organic template molecules used in the synthesis.

13-As stated in any of the claims above, the process for preparation of biomedical grade polyurethane composites containing antibacterial zeolites involves homogeneous mixing of dried zeolites with freshly prepared fluid prepolymer during the composite preparation step. 14- As stated in any of the claims above, the process for preparation of biomedical grade polyurethane composites containing antibacterial zeolites involves addition of zeolites 0.01-50 % by mass to polymer while preparing the composite.

15-As stated in any of the claims above, the process for preparation of biomedical grade polyurethane composites containing antibacterial zeolites involves addition of hydrophilic chemicals as expanding materials into the fluid composite, and when these chemicals react with the isocyanide groups, the polymeric structure expands, and biomedical grade spongy structures are obtained when the expanded form is cured at high temperatures. 16- As stated in any of the claims above, the process for preparation of biomedical grade polyurethane composites containing antibacterial zeolites involves addition of water into the fluid composites as the hydrophilic chemical that causes the expansion of the structure.

17-As stated in any of the claims above, the process for preparation of biomedical grade polyurethane composites containing antibacterial zeolites involves addition of other gases other gases in order to expand the polymer and form the spongy structure.

18-As stated in any of the claims above, the process for preparation of biomedical grade polyurethane composites containing antibacterial zeolites involves addition of air, oxygen, nitrogen, or helium as the gas that expands the polymer and forms the spongy structure.

19-As stated in any of the claims above, the process for preparation of biomedical grade polyurethane composites containing antibacterial zeolites involves no hydrophilic chemical or gaseous additions while preparing thin films with a smooth and shiny surface. 20- As stated in any of the claims above, the process for preparation of biomedical grade polyurethane composites containing antibacterial zeolites involves preparation of products in the form of films, sponges or fibers.