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24745

DESCRIPTION

A METHOD OF MANUFACTURING A DISPERSION CONTAINING SILVER ΝΑΝΟ PARTICLES AND ALSO THE USE OF A MIXTURE CONTAINING SILVER ΝΑΝΟ PARTICLES AS A COATING MATERIAL

Technical area

The invention relates to a coating material having a dispersed formulation containing silver nanoparticles, as well as a method for its manufacture and its use in particular as coating material.

State of the art

The biocide effect of silver is known. Especially in the medical field related to implants, the use of antibiotics is increasingly being tried to be reduced or the use of antibiotics to be eliminated completely. Here, silver offers an effective alternative.

Until now, it has long proven itself to be a problem that the added silver particles do not achieve a sufficient effect, especially in bone cement. This is presumed to be related in principle to the too small specific surface of the material used.

In principle, bone cement is a material that solidifies due to a polymerization reaction. Bone cement based on methylmethacrylate, for example, is known in practice. It basically consists of two components; that is, a liquid and a solid component. The solid component may comprise a substantially polymerized perlipolymericate as well as a polymerization initiator and other components by which, for example, the reaction rate is adjusted. The monomer component comprises a monomer or a prepolymer, through which a polymerization reaction is initiated, after which the liquid component is mixed with the solid component, the mass due to which the first pasty mass solidifies into a solid substance. Bone cement is used, for example, for the application of endoprostheses, for the manufacture of spacers, in multi-part prostheses, and for vertebroplasty and kyphoplasty. Bone cements with different strength properties and hardening properties can be offered each time according to the desired application purpose.

It is known to add an antibiotic, for example Gentamicin, to provide an antibiotic effect.

In bone cement and polymer-based coating materials, it is desirable to add silver additionally or alternatively to obtain an antimicrobial effect.

Due to the special properties, especially the larger specific surface, it is desirable to add nanoparticulate silver. An addition of nanoparticulate silver to solid components fails in principle because it is almost impossible to prepare nanoparticulate silver in a solid state, because it clumps.

The addition of silver in the liquid stage is also difficult because on the one hand there are clumping effects and furthermore, it has not been achieved so far to prepare a sufficiently robust dispersion with nanoparticulate silver which remains dispersed in covalent or less polar liquids such as methylmethacrylate.

According to a general definition, "nanoparticle" is a definition for particles having a size in the range less than 100 nm. The "nano" prefix thus creates a restriction to particles in the sub-micrometer range (> 100 nm) in accordance with the official definition according to ISO TC 229. In general, it should be noted that the substances defined as nanomaterials have altered, chemical and physical properties. In nano-metals, for example gold and silver, they have different colors from the respective metals, namely red or yellow.

Apart from that, it has been scientifically proven that the nanoparticles of a substance have an increased surface energy. The smaller the particles, the higher their surface energies. Consequently, nanoparticles should generally be handled in a non-rigid way because they react to new compounds or higher, stronger aggregates due to their high surface energies.

In the case of nano-metals, this means that even particles of noble metals are rapidly oxidized by oxygen in the air when the size of the particles is in the nanometer range.

That is, technologically usable nanoparticles can only be obtained when their surfaces are chemically or physically protected and thus consolidated. That is, nanoparticles that maintain or preserve their original particle size, from manufacturing to use, are defined as "technologically usable".

Possibilities for consolidating nanoparticles in dispersions are known from the prior art. There are three important methods for fabricating metallic nanoparticles. In a first method, the nanoparticles are conveyed over solids for consolidation. Solids are always present here in a fixed size in the micrometer range. On the one hand, the loss in the nano-level marrow and on the other hand the high filler load is disadvantageous in the use of products manufactured in this way. The filler used, which serves as the basis for the formation of metal nanoparticles, has grain sizes in the micrometer range and is completely unsuitable for manufacturing fine structures or fibers, for example. Also, in practice, the weight fraction of the filler is several times the nano metal fraction.

In flaming pyrolytic processes, the cluster of microparticles and nanoparticles emerges as solid matter, which must be laboriously redistributed before reuse, which is often no longer possible due to deposition effects. Apart from this, the distribution of nanoparticles can never be optimally achieved, since this can only be as good as the distribution of the microparticles on which they are separated.

A second method route exists in the synthesis of metal nanoparticles by consolidation with the aid of polymers such as polyvinylpyrrolidone in the polyol process, which is often described as the standard method in the literature. However, only low metal nanoparticle concentrations are achieved here (range less than 0.1 weight percent silver).

The third variation for creating metal nanoparticles is a PVD method (Physical Vapor Deposition), based on which the metal is evaporated. Polymers or silicones are also used to consolidate the nanoparticles produced in this way. Generation of metal vapor is a very energy consuming process, requiring evacuated process chambers. These manufacturing methods are thus uneconomical. In addition, the polymers and silicones used cause significant problems with the process technique during downstream processing, since a redistribution is often impossible.

Furthermore, it is known from the patent specification DE 10 2006 056 284 A1 to manufacture an aqueous dispersion with antimicrobial effect, an aqueous dispersion of nanoparticles containing at least one antimicrobial effect metal, by mixing with an aqueous dispersion of a polymerization, polycondensation or polyaddition product. The production of silver nanoparticles is carried out by means of a chemical reduction in water . Sodium chloride is used to consolidate the silver nanoparticles.

A disadvantage of all manufacturing variations is the poor processability of metal nanoparticles in polymer melts, such as when adding thermoplastic polymers. Solid materials cannot be processed homogeneously without pre-dispersing.

Therefore, there remains a need for robust dispersions of silver nanoparticles, also with antimicrobial properties.

Patent specification US 2008/181931 A1 shows the addition of a stabilizer and the formation of nanoparticles in the natural environment. Patent specification US 2007/003603 A1 shows the use of an aqueous or non-aqueous dispersion as coating material for implants. Patent specification JP 2008-231489 A shows the fabrication of nanoscale metal particles in micelles.

Presentation of the invention

The object of the invention, as described in the claims, is the preparation of stable dispersions of silver nanoparticles, which can be used in bone cement or as an antibacterial coating, in particular for implants and medical devices.

Dispersion is especially used in polymer-based bone cements and coating materials.

The object of the invention is solved by the use of a method for the production of a dispersion containing silver nanoparticles, a dispersion containing silver nanoparticles and also a mixture containing silver nanoparticles, according to one of the independent claims. Other advantageous details, features and designs of the present invention emerge from the dependent claims, description, examples and figures.

On the one hand, the invention relates to a method for manufacturing a dispersion containing silver nanoparticles. This dispersion should be used especially for implants and medical instruments, especially for the fabrication of bone cement or for a coating material. Moreover, a use as an antibacterial carrier material is envisaged both in the medical field and for clothing and articles of use.

In accordance with the invention there is provided a silver salt and a stabilizer.

In addition, a reducing material and an organically polymerizable solvent are provided. In particular, polymers or prepolymers are envisaged as organic polymerizable solvent, which can thus be used, for example, as a coating material or as a component of a bone cement.

A solution is formed from the silver salt, stabilizer, and reducing material.

After the solution has been manufactured, a base and also an inorganic salt are added.

With the addition of the base, dispersed nanoparticles result.

The water remaining in the solution is hydrated over the inorganic salt. An aqueous phase is now formed, whereas the silver nanoparticles remain predominantly in the organically polymerizable solvent due to the stabilizer added. The aqueous phase can now be separated, for example filtered, such that a polymerizable organic solvent with silver nanoparticles remains.

By means of the invention, a substantially anhydrous monomer or prepolymer containing silver nanoparticles, for example an acrylate, in particular methyl methacrylate or butylacrylate, can thus be prepared.

It is understood that a certain amount of water may remain in the organic solvent because small amounts of water can be dissolved in for example methyl methacrylate.

However, here a substantially organic polymerizable solution is molded, which can be used, for example, as a coating material or as a component, by a polymerizable material, in particular bone cement.

The invention also relates to a dispersion containing silver nanoparticles, in particular used as bone cement, as an antibacterial carrier material or as a coating material.

The silver nanoparticle-containing dispersion includes silver nanoparticles, at least one stabilizer and at least one wetting and dispersing additive, wherein the silver nanoparticles are dispersed in a liquid monomer, prepolymer or polymer.

The invention is based on the knowledge that it is possible to prepare a dispersion that remains stable over a long period of time in an organic liquid, for example an acrylate with silver nanoparticles, using a stabilizer and also another wetting and dispersing additive.

The stabilizer is preferably selected from the group consisting of polyoxyethylene-mono-alkyl acid ester, polyoxypropylene-mono-alkyl acid ester, polyoxyethylene-di-alkyl acid ester, polyoxypropylene-di-alkyl acid ester, polyoxyethylene-tri-alkyl acid ester, polyoxypropylene-tri-alkyl acid ester, and mixtures thereof. .

A non-ionic surfactant, in particular a silicon organic surfactant, is preferably used as the net and dispersing additive.

The inventors speculate that the nanoparticles are surrounded and surrounded by the stabilizer and then by the wetting and dispersing material as the second layer.

Since the stabilizer serves, especially in a first manufacturing step, that the nanoparticles emerge in an aqueous solution and do not agglomerate, the wetting and dispersing additive also ensures that the nanoparticles remain dispersed in a less polar organic liquid. The dispersion containing silver nanoparticles can be used, for example, as a monomer for a coating solution or as an additive for polymer materials, especially for the manufacture of bone cement.

In particular, an acrylate or an acrylate precursor, in particular methyl methacrylate, is used here as the polymer. In one embodiment, it consists of silver nanoparticles and polyoxyethylene-mono-alkyl acid esters, polyoxypropylene-mono-alkyl acid esters, polyoxyethylene-di-alkyl acid esters, polyoxypropylene-di-alkyl acid esters, polyoxyethylene-tri-alkyl acid esters and polyoxypropylene-tri-alkyl acid esters. A mixture of silver nanoparticles including at least one stabilizer selected from the group is used.

The mixture used for the bone cement or coating material according to the invention will be described in detail below.

In the present text, all expressions of parts by weight are used on a 100% basis with respect to the weight of the complete formulation.

The mixture used is at least from the group consisting of polyoxyethylene-mono-alkyl acid ester, polyoxypropylene-mono-alkyl acid ester, polyoxyethylene-di-alkyl acid ester, polyoxypropylene-di-alkyl acid ester, polyoxyethylene-tri-alkyl acid ester and polyoxypropylene-tri-alkyl acid ester. It contains a stabilizer. These stabilizers are compounds from the group of nonionic surfactants with borderline surface-active properties, which are present in liquid form at room temperature. Nonionic surfactants in the sense of the invention are boundary surface active chemical components that have uncharged polar and covalent regions in a molecule. Apart from that, nonionic surfactants do not have incompatible functional groups.

A mixture of silver nanoparticles according to the invention contains dispersion-stabilized silver nanoparticles, which do not clump into large lumps, since the stabilizers used are liquids in the temperature range of 0 - 240 ° C. In contrast, the state of the art keeps a large number of silver nanoparticulate products available and they are presented as dry powder, but due to their agglomeration tendency, they are only used under high mechanical energy input and then only incompletely to be dispersed in organic solvents such as methylmethacrylate during transport and storage. they can be redistributed.

For use in the present invention, combinations of the boundary surface-active ingredients from the aforementioned class of chemicals are particularly preferred. That is, according to a particularly preferred embodiment, at least two stabilizers are present in the mixture.

While a large number of stabilizers are present, different stabilizers from one of the classes of chemical compounds referred to herein or stabilizers of different classes of compounds may be involved. That is, three different polyoxyethylene-monoalkyl acid esters can be used in a combination of three different stabilizers; however, for example, two different polyoxyethylene-mono-alkyl acid esters and a polyoxypropylene mono-alkyl acid ester or, for example, a polyoxypropylene-di-alkyl acid ester, a polyoxyethylene-tri-alkyl acid ester and a polyoxypropylenetri-alkyl acid ester can also be used. Any desired combination of these nonionic surfactants is possible.

Particularly preferably, the mixture of stabilizers consists of a combination of nonionic surfactants from two different classes of compounds mentioned above.

According to a particularly preferred embodiment, the stabilizers or stabilizers are polyoxyethylene-sorbitan monolaurate, polyoxyethylenesorbitan-monopalmitate, polyoxyethylene-sorbitan-monostearate, polyoxyethylene-sorbitan-monooleate, polyoxyethylene-sorbitan-glyphearate, polyoxyethylene-triethylene-glyceroleate. , polyoxyethylene-glyceryl-monooleate, polyoxyethylene-glyceryl-monostearate, polyoxyethylene-glyceryl-monoricinoleate, castor oil, They were selected from the group consisting of hydrated castor oil and soybean oil.

Stabilizers are often not known by their chemical name, but rather by their commercial team names. Stabilizers preferred within the scope of the present invention are Tween20 ™, Tween40 ™, Tween60 ™, Tween80 ™, Polysorbat ™, Tagat TO ™, Tagat TO V ™, Tagat L2 ™, Tagat S2 ™, Tagat R40 ™, Triton X 100 ™, Hydrogenated Castoroil ™. PEG 20 Glycerylstearate ™, PEG 20 Glyceryllaurat ™, PEG 40 Castoroil ™, PEG 25 Glyceryltrioleat ™, Newcol ™, Montane ™, Lonzest ™, Liposorb ™, Nonion ™, Kuplur ™, lonet ™, Chemotan ™, Grillosan ™, Ethylan ™ , Glycomul ™,

Emsorb ™, Disponil ™, Amisol ™, Armotan ™, Sorbax ™, Sorbitan ™, Span ™ and Tego Pearl ™.

This list of stabilizers is not exhaustive, because different manufacturers market the same or similar products under other names, or new nonionic surfactants from the aforementioned classes of compounds are synthesized in the future and can likewise be used in a mixture according to the invention.

If at least two stabilizers are present in the mixture, then they are preferably present in the mixture in some ratio in the range from 1: 1 to 2: 1.

Since the nonionic surfactants contained in the mixture act as stabilizers for the nano-metal formed, there is some relationship between the concentrations of the stabilizers and the metal. According to another preferred embodiment, the ratio of the amount of silver nanoparticle stabilizer is between 10: 2 and 10:50, particularly preferably between 10: 5 and 10:10. If there is more than one stabilizer, then the concept of "metal stabilizer quantity ratio" should be understood as "the ratio of the total amount of stabilizers present to metal". By using the preferred amount ratios, mixtures are obtained from which particularly stable dispersions, which are universally usable, can be formed, in particular from metal nanoparticles. Preferably the metal nanoparticles have a particle size between 1 and 100 nm, particularly preferably between 1 and 50 nm, particularly preferably between 1 and 20 nm.

The present invention relates to a formulation containing silver nanoparticles, comprising dispersion of one of the mixtures containing metal nanoparticles described above. The formulation according to the invention is liquid and furthermore does not contain any solid additional ingredients that would limit its continued use.

In the mixture according to the invention and also in the formulation according to the invention, one or more boundary surface-active components are included as stabilizers, which, in addition to stabilizing the silver nanoparticles, allow further processing (redispersion, emulsification) of all other substrates. Technologically attractive to continue processing is processing in thermoplastic plastics. The temperatures used here reach up to 300 ° C. Up to this temperature, it is desired that the formulation to be used as the additive be liquid, this is accomplished by the use of one or more boundary surface active ingredients which are liquid for a short time to a temperature of 300 ° C. Particularly preferably, at least two stabilizers are present in the formulation. If a large number of stabilizers are available, it may be one of the classes referred to here as chemical compounds or stabilizers from different classes of compounds. That is, three different polyoxyethylene mono-alkyl acid esters can be used in a combination of three different stabilizers; however, for example, two different polyoxyethylene-mono-alkyl acid esters and a polyoxypropylene mono-alkyl acid ester or, for example, a polyoxypropylene-di-alkyl acid ester, a polyoxyethylene-tri-alkyl acid ester and a polyoxypropylenetri-alkyl acid ester can also be used. Any desired combination of these non-ionic surfactants is possible.

Particularly preferably, the mixture of stabilizers consists of a combination of nonionic surfactants from two different classes of compounds mentioned above.

There is some relationship between the concentrations of the stabilizer and the silver, as at least one nonionic surfactant is used as a stabilizer for the nano-metal formed. For example, the formulation according to the invention for use in methyl methacrylate has an amount ratio of silver to stabilizer in the range 10: 2 to 10:50. Preferably the ratio of metal to stabilizer is between 10: 5 and 10:20, particularly preferably between 10: 6 and 10:10. If more than one stabilizer is present, then the "metal to stabilizer ratio" should be understood as the "ratio of the amount of metal to the total of the stabilizers available". Particularly stable dispersions of silver nanoparticles are obtained by using the preferred amount ratio. Preferably, more than two stabilizers are present in the formulation according to the invention. In this case, the content of a first stabilizer is in the range 30 to 90% by weight, preferably 40 to 60% by weight, particularly preferably 45 to 55% by weight. The residual weight fraction of up to 100 percent is allocated to other stabilizers according to the invention used in combination, which are divided in their respective quotations between 0 and 100% by weight. The weight percent information referred to herein thus, unlike other information, relates to 100% total weight of the stabilizers.

Particularly preferably, one or more stabilizers selected from the group consisting of Tagat TO V ™, Tween20 ™, Tween80 ™ and Tagat L2 ™ are present in the formulation. Particularly robust and universally usable dispersions are obtained from the use of these stabilizers.

According to a particularly preferred embodiment of the present invention, a mixture of Tagat TO V ™ and Tween20 ™ is present as stabilizer in the formulation. Formulations where the ratio of Tagat TO V ™ to Tween20 ™ is in the range of 1: 2 to 2: 1 are particularly preferred, and formulations where the ratio of Tagat TO V ™ to Tween20 ™ is about 1: 1 is particularly preferred. is.

As regards particle size, reference is made to the definition formulated at the re-entry, whereby silver nanoparticles have a particle size of less than 100 nm. In the formulation according to the invention, the silver nanoparticles are present in a particle size between 1 and 100 nm, preferably between 1 and 50 nm, particularly preferably between 1 and 20 nm. The morphology of silver nanoparticles can here be in the shapes of triangles, cubes, spheres, bars, or small plates.

Preferably, the formulation contains solid, nanoscale metal particles in a concentration of 0.5 to 60% by weight, wherein the ratio of silver nanoparticles to stabilizer is in the range of 10: 2 to 10:50, preferably 10: 5 to 10:10. . In preferred ranges, dispersions of particularly stable silver nanoparticles can be obtained which can be used universally.

The silver nanoparticles are particularly preferably contained in the formulation in a proportion of between 1 and 40% by weight, preferably between 5 and 30% by weight. An organic solvent is used to manufacture the dispersion. That is, it is a dispersion of a mixture containing silver nanoparticles, described in more detail above, in an organic solvent. Very particularly preferably methyl methacrylate is present in the organic solvent.

The present invention also includes the preparation of a metal salt, polyoxyethylene-mono-alkyl acid ester, polyoxypropylene mono-alkyl acid ester, polyoxyethylene-di-alkyl acid ester, polyoxypropylenedi-alkyl acidester, polyoxyethylenetri-alkyl acid ester, as described above, containing metal nanoparticles. preparing at least one stabilizer selected from the group consisting of polyoxypropylene-trialkyl acid ester, preparing a reducing material, It also includes a method comprising the steps of preparing a solvent, making a solution from metal salt, stabilizer and reducing material, adding a base to the solution, where the addition of the base is continuously over the time interval of 5 to 48 hours, the pH of the formulation is 0 and 6. between.

By means of the manufacturing method according to the invention, a formulation with a very narrow distribution of the particle size of the nanoparticles is obtained. An organic solvent is used as a solvent.

Preferably the addition of the base is carried out in a time interval between 9 and 30 hours. In this way, a formulation with a particularly narrow distribution of the particle sizes of the nanoparticles is obtained.

The manufacturing method according to the invention is a chemical reductive process. Accordingly, silver particles are produced from their salts by chemical reduction. In general, any desired chemical or physical reduction material can be used to manufacture the silver nanoparticles according to the invention. The concept of physical reduction material is to be understood here as an increase in temperature or radiation by light. The use of a chemical reducing material is advantageous because material gains of 100 percent and very high reaction rates can be achieved here.

Surprisingly, at least one stabilizer from the polyoxyethylene-mono-alkyl acid ester, polyoxypropylene-mono-alkyl acid ester, polyoxyethylene-di-alkyl acid ester, polyoxypropylene-di-alkyl acid ester, polyoxyethylene-tri-alkyl acid ester and polyoxypropylene-tri-alkyl acid ester group It has been found that very strong reduction materials can be used in the presence of this, which is simultaneously large, It results in an elevated reaction rate without the danger of the formation of a large proportion of undesirable silver particles.

Of the chemical reduction materials, those that do not create any more reaction additives are preferred, such as the corresponding oxidized form of the reducing material in the reaction mixture, which would degrade the dispersed aqueous formulation, containing silver nanoparticles. According to a preferred embodiment, a reducing material is therefore used which reacts with the metal ions of the metal salt under basic metal formation and under the formation of predominantly gaseous reaction products in the remainder.

Reducing materials, such as hydrasynhydrate, are particularly preferred, which in their oxidized form can leave the reaction solution as a gaseous substance. Of course, the silver nanoparticles according to the invention can likewise be obtained with any other desired reducing material.

The reductive manufacture of metals can be formulated as a pair of redox equations. The first partial equation is the reduction equation, whereby the metal cation from the metal salt is reduced to the element metal. The second partial equation describes the corresponding oxidizing process for oxidizing the reducing material to the conjugating oxidation product, which ideally leaves the reaction solution in the gaseous state. What all reduction materials have in common is that one proton is formed per electron transferred. This proton contributes to a very strong drop in the pH of the complete reaction solution. Here, the lowering of the pH value causes the reaction to collapse undesirably. Therefore, a base must be added to capture the protons that occur, which will brake the complete reaction.

Surprisingly, it has been found that the type of base, the concentration of the base, and the rate at which the base is added are decisive for the dispersion of the nanoparticles in the manufactured formulation.

Preferably, ammonia, potassium hydrogen carbonate or sodium hydroxide are used as the base. If these bases are used, particularly robust dispersions with a narrow distribution of the particle size of the nanoparticles are obtained.

The amount of base added here must be measured in such a way that a pH-neutral dispersion is obtained after the reaction is terminated. Here the pH value is then between pH 5 and pH 9.

Bases or proton acceptors pK_b they are defined by their value. Where pK_b is the simple negative logarithm of the proton concentration at equilibrium and is thus a measure for basicity.

In order to produce the formulation according to the invention, a pK in the range of -2 to 10.5, preferably 1.5 to 9.1, particularly preferably 3.5 to 7.5_b Bases having the value are suitable.

Besides the basicity, the rate of addition into the reaction solution is decisive for the manufacture of the formulation according to the invention. If the addition occurs too quickly, then the particle size range shifts to larger particles in the extreme case in the micrometer range. If, on the other hand, the addition takes place too slowly, then material yields of more than 90% are not obtained, because the already formed nano-metal catalytically decomposes the reducing material so that there is no longer a reaction partner for the creation of silver nanoparticles.

Experiments have shown that the rate of addition of the base should be in the range of 9 to 30 hours in order to ensure the inventive high quality of silver nanoparticles with a planned size of 50 kg. Correspondingly, the base addition time is also shortened for low planned sizes. The upward addition time cannot be expanded if desired, because catalytic decomposition of the reducing material significantly adversely affects the overall yield after 48 hours at the latest by the nanogenic already formed.

The rate of addition of the base is carried out so that the pH of the dispersion is between 0 and 6. A higher pH value causes a rapid reaction and thus uncontrolled particle growth. Too low a pH value will cause the reaction to collapse so that no more nanometers are formed.

The formulation according to the invention can be used in a large number of applications, with distinctly advantageous properties in the most varied uses. The metal nanoparticles of the formulation according to the invention or the metal nanoparticles of the formulation produced according to the method according to the invention can be processed into different substrates in particular to obtain antimicrobial activity.

The present invention also relates to a method of manufacturing bone cement or a coating material for implants or medical instruments with one of the mixtures containing silver nanoparticles described in more detail above. wherein an inorganic salt is added to one of the formulations containing silver nanoparticles described in more detail above, or an inorganic salt is added after carrying out one of the methods described in more detail above to manufacture a formulation containing silver nanoparticles, wherein inorganic salt, It includes at least one element of the fourth or fifth major group of the periodic element system as component of the anion.

The present invention

- silver nanoparticles and polyoxyethylene-mono-alkyl acid ester, polyoxypropylene-mono-alkyl acid ester, polyoxyethylene-di-alkyl acid ester, polyoxypropylene-di-alkyl acid ester, polyoxyethylene-mono-alkyl acid ester, polyoxyethylene-di-alkyl acid ester, polyoxypropylene-di - comprising at least one stabilizer selected from the group consisting of alkyl acid ester, polyoxyethylene-tri-alkyl acid ester and polyoxypropylene-tri-alkyl acid ester, It includes a method for manufacturing a mixture containing silver nanoparticles, which includes the following steps.

- preparation of a silver salt,

- preparation of at least one stabilizer selected from the group consisting of polyoxyethylene-monoalkyl acid esters, polyoxypropylene-mono-alkyl acid esters, polyoxyethylene-di-alkyl acid esters, polyoxypropylenedi-alkyl acid esters, polyoxyethylene-tri-alkyl acid esters, polyoxypropylene-tri-alkyl acid esters and mixtures thereof ,

- preparation of a reduction material,

- preparation of a solvent,

- manufacture of a solution of silver salt, stabilizer and reduction material,

adding a base to the solution, wherein the addition of the base is carried out continuously over a time interval of 5 to 48 hours, such that the pH of the formulation is between 0 and 6,

the addition of an inorganic salt, wherein the inorganic salt comprises at least one element from the fourth or fifth main group of the periodic elements system as the component of the anion.

That is, a mixture containing nanoparticles according to the invention can be derived from a formulation containing the corresponding nanoparticles by adding an inorganic salt.

In particular, the addition of an inorganic salt is associated with very particular advantages in manufacturing the mixture containing nanoparticles from a nanoparticle-containing formulation obtained by reduction of a silver salt in solution. Surprisingly, it has been found that by adding inorganic salts, the dispersion obtained by adding a base to a solution from the silver salt, stabilizer and reducing material separates into two chemical phases 1 and 2. Phase 1 contains silver nanoparticles in the liquid stabilizer mixture used herein. The solvent, inorganic salts and by-product ammonium nitrate are present in phase 2 above phase 1. Both phases are now easily separated from each other; For this, the upper phase is separated from the 2 residue. Now only phase 1, which consists of silver nanoparticles and liquid stabilizers, remains.

Chemically stabilized silver nanoparticles, which are available in the form of a dispersion, principally with particle sizes between 1 and 20 nm, are thus separated from the by-product ammonium nitrate contained in the dispersion and from the solvent used. The silver nanoparticle formulations according to the invention can thus be made accessible to additional fields of application.

In order to characterize suitable salts in more detail, the cationic and anionic components must be considered separately. Salts generally consist of at least one cation and at least one anion. An undesirable interaction of the cations with the formulation containing the stabilized metal nanoparticle is not expected, since the silver used is present either as the uncharged metal or as the positively charged cation.

The choice of anions is also limited in that their undesired interactions with the silver cations present must be avoided. Thus, with the silver used, all cations forming heavily soluble compounds, ie halogenides, calogenites and their oxygen compounds, are separated.

Particularly preferably, the inorganic salt therefore includes as component of the anion at least one element of the fifth major group of the periodic elements system, where particularly preferably the inorganic salt comprises nitrogen as the component of the anion.

Particularly preferably, the phase formed after the addition of the inorganic salt is separated from the mixture consisting essentially of silver nanoparticles and stabilizers, leaving a residue of silver nanoparticles.

The present invention further comprises the steps of preparing one of the mixtures containing silver nanoparticles described in more detail above, preparing a solvent, adding the mixture containing silver nanoparticles to the solvent, which is described in more detail above. It relates to a method for manufacturing one of the formulations. That is, the present invention consists of silver nanoparticles and polyoxyethylene-mono-alkyl acid ester, polyoxypropylene-mono-alkyl acid ester, polyoxyethylene-di-alkyl acid ester, polyoxypropylene-di-alkyl acid ester, polyoxyethylene-tri-alkyl acidester and polyoxypropylene-tri-alkyl acid ester. for the manufacture of a formulation containing silver nanoparticles, comprising a dispersion of a mixture of silver nanoparticles comprising at least one stabilizer selected from the group. silver nanoparticles and polyoxyethylene-mono-alkyl acid ester, polyoxypropylene-mono-alkyl acid ester, polyoxyethylene-di-alkyl acid ester, polyoxypropylene-di-alkyl acid ester, polyoxyethylene-tri-alkyl acid ester and polyoxypropylene-tri-alkyl acid ester. preparing a mixture containing silver nanoparticles including at least one stabilizer, preparing a solvent, It includes a method comprising the steps of adding the mixture containing silver nanoparticles to the solvent.

The chemically stabilized silver nanoparticles according to the invention can be wetted or dissolved by solvent without losing the stabilizer cover required for stabilization. The solvent is an organic solvent. All organic, proton, non-proton, polar and covalent compounds or mixtures thereof can be used here.

In accordance with a particularly preferred embodiment of the present invention, at least one wetting and dispersing additive is additionally added. The wetting and dispersing aid ensures that the silver nanoparticles are wetted by the solvent used.

Suitable chemical compounds that can be used as wetting and dispersing additives are alkylphenol ethoxylates, amino functional polyester, phosphorus containing substances such as organically modified phosphates, phosphonates, polyphosphorus compounds and alkylphosphonates or a mixture of these compounds.

Particularly preferably, the wetting and dispersing additive is an organically modified phosphate, a phosphonate, a polyphosphorus compound, an alkylphosphonate, a phosphorus compound with mixed organic ligands, an oligomer with phosphate-containing ligands or a polymer.

Such wetting and dispersing additives are offered by Evonic, BYK Chemie and Ciba Geigy companies.

That is, chemically stabilized silver nanoparticles with a preferred particle size of 1-20 nm can be processed with the aid of wetting and dispersing additives, especially in organic solvents, especially methyl methacrylate. This can be accomplished by the simplest mixing and mixing techniques, since the redispersing of the metal nanoparticles is not necessary through the use of stabilizers according to the invention. In this way, stable dispersions with a particle size of less than 20 nm are obtained, for example, of silver nanoparticles in an organic solvent, preferably methyl methacrylate, at a concentration of silver content of 5,000 mg / kg to 50,000 mg / kg.

In particular, the invention relates to a bone cement, an antibacterial carrier material or a coating material, in particular an acrylate-based coating material that can be manufactured by the method described above.

The invention also relates to a bone cement comprising silver nanoparticles, an antibacterial carrier material or a coating material for implants or medical devices.

Coating material A particularly liquid coating material, for example an acrylate or silicone. The coating material can be applied, for example, by dipping (dipcoaten).

The nanoparticles according to the invention are surrounded by at least a first and a second stabilizer and dispersed in a polymer.

A polymer is understood here in the form of a prepolymer in any form, as well as essentially a not yet made monomer solution, for example containing methyl methacrylate by weight.

The inventors have found that by the use of two different stabilizers, in particular by using two emulsifiers, it is possible to prepare a stable dispersion that can also be preserved in covalent liquids.

Particularly suitable as the starting material is the formulation described above, which is considered to include silver nanoparticles already having a sheath of at least one stabilizer.

However, it cannot always be ensured that there is no sedimentation and clumping in this formulation.

However, the inventors have found that it is possible to prepare a stable dispersion in a covalent liquid by the choice of a second stabilizer that is supposed to be placed around the first stabilizer like a second sheath.

For this, a non-ionic surfactant, in particular an organic surfactant with silicon, is used. Such a surfactant is available, for example, under the trade name Tego DISPERS 655.

In particular, at least 0.1%, preferably at least 0.2% of the second stabilizer is added to the mixture, ie the monomer component of a bone cement or coating solution. The goal is to keep the amount of additional chemicals as low as possible.

The inventors have found that less than 1%, preferably less than 0.2, is sufficient to stabilize nanoparticles with an average particle size between 5 and 50, preferably between 10 and 20 nm.

Thus, a dispersion is prepared in which at least 90%, preferably at least 99 of the silver nanoparticles are less than 50, preferably less than 20 nm.

Preferably, the nanoparticles have a substantially spherical shape, in which a spherical shape is understood in the sense of the invention in which the length, width and height of the particles differ from each other by less than 20%, so that they are not, for example, needle shaped particles.

Polymer-based coatings or bone cements are prepared which have an antimicrobial effect and in which antibiotic use is at least reduced or even antibiotics can be completely dispensed with, with a proportion of silver nanoparticles in the polymer, in particular between 0.5 and 5, preferably between 1 and 3% by weight.

The present invention also encompasses the use of the formulation according to the invention for the treatment of surfaces of implants and medical devices. The particular advantages obtained with such use will be described in more detail in the following examples.

In particular, the present invention encompasses the use of the formulation according to the invention for manufacturing antimicrobial surfaces. The particular advantages obtained with such use will be described in more detail in the following examples.

The present invention also covers the use of the formulation according to the invention in silicones as coating material. The particular advantages obtained with such use will be described in more detail in the following examples.

The present invention also includes the use of the formulation according to the invention in thermoplastic plastics, preferably polypropylene. The particular advantages obtained with such use will be described in more detail in the following examples.

The present invention also includes the use of the formulation according to the invention in duroplasts, preferably for the manufacture of PMMA bone cement. The particular advantages obtained with such use will be described in more detail in the following examples.

The present invention also includes the use of the formulation according to the invention to manufacture PMMA coatings. The particular advantages obtained with such use will be described in more detail in the following examples.

Brief description of the drawings

For the illustration of the invention and to clarify its advantages, application examples are shown below.

These application examples are described in more detail in connection with the drawings. It should be understood here that this information does not limit the invention. Here

Figure 1 shows a UVvis spectrum of an aqueous solution of a formulation according to the invention, diluted 5,000 times,

Figure 2 Scanning Electron Microscope (SEM) - measured particle sizes and calculated curve of data lines,

Figure 3 Transmission Electron Microscope (TEM) analysis of silver nanoparticles.

Figure 4 is a transmission electron microscope image (TEM) of an aqueous solution of a formulation according to the invention, diluted 5,000 times,

Figure 6 is a transmission electron microscope image (TEM) of a coated felt / foil laminate.

Figure 7 shows the kinetics of bacteria (E.coli) killing applied on the coated felt in Figure 6.

Figure 8 A transmission electron microscope image (TEM) of a polyester mastermix with 6500 mg / kg of silver.

Figure 9 Microfibre rods of PET / PA with 200 mg / kg,

Figure 10 shows the elution characteristic and antimicrobial activities of various polyester microfibers.

The following examples are not according to the invention.

Example 1:

Formulation of nano silver with hydrasynhydrate, ammonia, Tagat TO V ™ and Tween20

7.000 g silver nitrate, 1.760 g Tagat TO V ™, 1.760 g Tween20 ™ and 512 g hydrasynhydrate are mixed in 28.439 g deionized water. The solution is stirred for 3 hours. Then 5,000 g of ammonia solution (14%) is added dropwise continuously over a 24 hour period. The reaction is complete after the addition taking place and provides a dispersion with a silver content of 10% by weight. Particle size and distribution are determined with the aid of a UVvis spectrum (figure 1). The result is a 10 percent Tuk nanosilver dispersion with a nanosilver particle size of 1 - 30 nm.

The absorption spectrum was carried out in an aqueous solution, diluted 5,000 times, that contained 20 ppm of nanosilver, clear and colored dark yellow. The UVvis spectrum is recorded in the wavelength range between 750 and 350 nm. The measured absorbance values ​​provide a peak with a maximum of around 410 - 420 nm and a peak half-value width of about 80 nm.

The dispersion properties of the resulting 10 percent dispersion are excellent in both polar and covalent solvents; That is, this means that a clear solution is obtained with a coloration caused solely by the plasmon effect of silver, without any further chemical consumption (dispersion aids) or without mechanical consumption (ultrasound, ultraturax, etc.).

Figure 4 shows a transmission electron microscope image (TEM) of the diluted dispersion of example 1. The dark regions visible in Figure 4 correspond to nanosilver particles having a particle size of 1-30 nm.

Example 2:

Formula A sy ten of nano silver with hydrasynhydrate, ammonia and Tagat TO V ™

7,000 g of silver nitrate, 3,520 g of Tagat TO V ™ and 1,331 g of hydrasinsulfate are mixed in 27,620 g of deionized water. The solution is stirred for 3 hours. Then 5,000 g of ammonia solution (14%) is added dropwise continuously over a 24 hour period. The reaction is complete after the addition taking place and provides a dispersion with a silver content of 10% by weight.

Particle size and distribution are determined with the aid of a UVvis spectrum. The result is a 10 percent nanosilver dispersion with a nanosilver particle size of 1-30 nm.

Example 3:

Formulation of nano silver with hydrous sulfate, potassium hydrogen carbonate, Tagat TO V ™ and Tween80 ™

7,000 g of silver nitrate, 2,360 g of Tagat TO V ™, 1,160 g of Tween80 ™ and 1,331 g of hydrazine sulfate are mixed in 27,620 g of deionized water. The solution is stirred for 3 hours. Then 5,000 g potassium hydrogen carbonate solution (1,900 g KHCO₃) It is added dropwise continuously over a period of 30 hours. The reaction is complete after the addition taking place and provides a dispersion with a silver content of 10.0 weight percent. Particle size and distribution are determined with the aid of a UVvis spectrum (figure 1). The result is a 10 percent nanosilver dispersion with a nanosilver particle size of 1 - 30 nm.

Example 4:

Formulation of nano silver with glucose, sodium hydroxide, Tagat L2 ™ and Tween20 ™

7,000 g of silver nitrate, 2,360 g of Tagat L2 ™, 1,160 g of Tween20 ™ and 3,708 g of glucose are mixed in 25,243 g of deionized water. The solution is stirred for 3 hours. Then, 5,000 g of sodium hydroxide solution (760 g of NaOH) is added dropwise continuously over a 30 hour interval. The reaction is complete after the addition taking place and provides a dispersion with a silver content of 10.0 weight percent. Particle size and distribution are determined with the aid of a UVvis spectrum. The result is a 10 percent nanosilver dispersion with a nanosilver particle size of 1 - 30 nm.

Example 5:

Formulation of nano copper with hydrasynhydrate, ammonia, Tagat TO V ™ and Tween20 ™

10,000 g of copper (II) nitrate, 1,760 g of Tagat TO V ™, 1,760 g of Tween20 ™ and 1,090 g of hydracinhydrate are mixed in 14,260 g of deionized water. The solution is stirred for 3 hours. Then 5,000 g of ammonia solution (14% Sal) is added dropwise continuously over a 24 hour period. The reaction is complete after the addition taking place and provides a dispersion with a copper content of 10.0 weight percent.

Example 6:

Continuing to process the dispersion of Example 1 to produce a liquid, anhydrous and salt-free formulation with silver nanoparticles.

The aqueous dispersion containing the silver nanoparticles obtained in Example 1 was contaminated with the by-product ammonium nitrate. Silver nanoparticles have particle sizes in the range of 1 - 20 nm and are chemically stabilized. The silver content is 25% by weight. The water content is 366 g and the ammonium nitrate content is 185 g. 1.000 g of this dispersion are poured into a beaker and, with mixing,^GIt is heated to C. The separation of the dispersion into two phases is initiated by adding 78 g of potassium nitrate. After the addition is complete and the potassium nitrate has completely dissolved, the heater is removed and the mixer turned off. Separation of phases can be observed after cooling. The top, clear, aqueous phase 1 is separated from the complete residue. The remaining phase 2 has a dark brown color with a slurry flow characteristic and a weight of 449 g. The stable dispersion is now ready for processing into an optional organic solvent, especially methylmethacrylate.

An analysis of the aqueous phase 1 results in a salt content of 263 g and a water content of 366 g.

Analysis of the silver-containing phase 2 gives the following data:

a) Analysis of the total silver content by incineration at 800 ° C yields 250 g of silver. With regard to the total formulation, this corresponds to a silver content of 56% by weight.

b) The analysis of the particle size distribution of the silver obtained is shown in Figure 1. The determination is determined by measuring the UVvis absorption spectrum in the wavelength range of 700 nm to 350 nm. The peak maximum at 415 nm corresponds to a particle size of 10 nm. The peak half-value width of maximum 80 nm is a measure for narrow particle size distribution. Correlation with SEM (Scanning Electron Microscope) and TEM (Transmission Electron Microscope) analyzes, as shown in Figure 2 and Figure 3, allows to indicate the particle size distribution of D 100 <20 nm (100% of particle diameters 20 nm '). less than).

Example 7:

Silver dispersion of Example 1¹ Continuation of processing to produce a liquid, anhydrous and salt-free formulation with nanoparticles

The aqueous dispersion containing the silver nanoparticles obtained in Example 1 was contaminated with the by-product ammonium nitrate. Silver nanoparticles have particle sizes in the range of 1 - 20 nm and are chemically stabilized. The silver content is 10 weight percent. The water content is 746 g and the ammonium nitrate content is 74 g. Separation of the dispersion into two phases is initiated by adding 202 g of potassium nitrate. After the addition is complete and the potassium nitrate has completely dissolved, the heater is removed and the mixer turned off. Separation of phases can be observed after cooling. The top, clear, aqueous phase 1 is separated from the complete residue. The remaining phase 2 has a dark brown color with a slurry flow characteristic and a weight of 180 g. The stable dispersion is now ready for processing into an optional organic solvent, especially methylmethacrylate.

An analysis of the aqueous phase 1 results in a salt content of 276 g and a water content of 746 g.

Analysis of the silver-containing phase 2 gives the following data:

a) Analysis of the total silver content by incineration at 800 ° C yields a result of 100 g of silver. With regard to the total formulation, this corresponds to a silver content of 55% by weight.

b) The analysis of the particle size distribution of the silver obtained is shown in figure 1. The determination is determined by measuring the UVvis absorption spectrum in the wavelength range of 700 nm to 350 nm. The peak maximum at 415 nm corresponds to a particle size of 10 nm. The peak half-value width of maximum 80 nm is a measure for narrow particle size distribution. Correlation with SEM (Scanning Electron Microscope) and TEM (Transmission Electron Microscope) analyzes, as shown in Figure 2 and Figure 3, allows to indicate the particle size distribution of D 100 <20 nm (100% of particle diameters 20 nm '). less than).

Example 8:

Use of the find-compliant formulation for pal's surface marking

From Example 1, the dispersion according to the invention is processed into conventional linseed oil (as regards the silver content in the finished product) to a concentration of 100 mg / kg as is known in the prior art. A stable dispersion of nanoparticles suitable for the surface treatment of wood is obtained.

Equipped with wood oil with additives, wood is resistant to many chemicals and water. Apart from that, wooden surfaces are protected against invasion by microorganisms; This means that microbes applied on the described surfaces die faster than surfaces with additives without wood oil.

Example 9:

The use of the inventive formulation to stimulate the growth of plants

The dispersion from Example 1 is preferably dispersed in water in a concentration of 1-100 pg / kg (with respect to the silver content in the finished product). A stable dispersion of nanoparticles that can be used to stimulate the growth of plants is obtained.

Effect of aqueous nanosilver dispersion on plant growth, Scenedesmus sp. with the help of an algae growing experiment. The results of the experiment are shown in figure 5. Figure 5 shows the test period after the nano-silver addition performed in the abscissa. In the ordinate, the optical density (OD) of the culture in proportion to the biomass concentration (algae concentration) at a wavelength of 510 nm is shown. Here, cultures without nanosilver addition (0 ppb nAg) and cultures with different nanosilver contents (0: 1 ppb, 10 ppb, A: 100 ppb and 1000 ppb) were investigated for algae growth.

As shown in Figure 5, algae grow exponentially to an OD of about 2.5 in the first 42 hours of cultivation without the addition of nanosilver. Then growth stops. The OD of the non-additive culture stabilizes at approximately 3. The additive culture with 1 pg / kg of nanosilver shows a similar course to the culture without additives in the first 42 hours of the experiment. The growth of the non-additive culture was almost finished at 42 hours and 75 hours at the end of the experiment, while the additive cultures with 1 mg / g nanosilver continued to grow without slowing during this time period and reach a final OD of 4.7.

Algae cultures with pg / kg or 100 pg / kg additive had a significantly increased algae growth after 25 hours compared to cultures without additives. Algae grow best in a nano-silver addition of 10 ppb. The final value reached at the end of the 75 hour test period is an OD of 5.4. Thus, in this experiment, an 80% increase in growth is evidenced by the addition of 10 pg / kg of nanosilver to Scenedesmus sp. At the end of 75 hours of cultivation versus an algae culture without additives. When 1000 pg / kg of nano-silver is added to the culture, silver has a toxic effect on algae. Algae added at the beginning of the experiment die quickly.

Example 10:

Use of the inventive formulation to manufacture antimicrobial surfaces

The dispersion from Example 1 is coated onto metal surfaces, for example titanium, with the aid of plasma electrolytic oxidation, preferably in a concentration of 5-50 g / kg silver. Strong antimicrobial active (R value> 3) surfaces are obtained.

Example 11:

Use of the inventive formulation to manufacture coatings for felt / foil laminates

The nanosilver dispersion from the sample is processed at a concentration of 150 mg / kg (with respect to the silver content in the coating) into the fluorine polymer dispersions specified in the market as known in the state of the art, designated for coating foils. A dispersion is obtained from stable, slightly yellow-colored nanosilver particles and fluorine polymer particles. The coating is applied on a PP-twist felt / foil laminate and thermally dried / set / wetted.

Figure 6 shows a TEM image of the coating with nanosilver. Typically 20 nm in size nanosilver particles (black dots in TEM image) were not agglomerated and were very evenly distributed within the polymer coating.

Figure 7 shows the kinetics of bacteria (E. coli) killing applied on the coated felt / foil laminate. At the end of 3.5 hours, 9O% of the applied bacteria were killed.

Table I shows the result of a microbiological test for the felt / foil laminate described in accordance with JIS 2801. 2x10 each time in the test⁵ Bacteria are applied on a felt / foil laminate coated with nanosilver, on an uncoated felt / foil laminate and on a standard polystyrene surface. At the end of the 18-hour growing period, the number of viable bacteria is determined. In summary, it can be said that the amount of bacteria on the nanosilver coated felt / foil laminate is reduced by 99.8% compared to standard polystyrene, where the uncoated felt / foil laminate does not have any bacterial reduction within the biological fluctuation width. Thus, the nano silver coated felt / foil laminate is considered to be strongly antimicrobial effective.

Table 2 shows the result of determining the anti-mycotic activity of the nano silver coated felt / foil laminate. In summary, it was found here that the nano silver coated felt / foil laminate showed significant activity against the 5 fungi tested.

Table 1: Microbiological test for nanosilver-coated felt / foil laminate with 150 ppm silver in the coating according to JIS 2801

one. test result at the end of the hour

Average amount of bacteria

<td>Vaccine</td><td>(cfu) 2, lxl0⁵</td>

<td>After 18 hours</td><td>Average bacteria F Value amount of</td>

<td>Internal standard (polystyrene)</td><td>(cfu) 1.12 2,8xl0⁶</td>

Double determination of independent samples

<td>After 18 hours</td><td>Average bacteria% reduction R Value amount of ¹</td>

<td>Felt / foil laminate with nano silver coating Nano silver uncoated felt / foil laminate</td><td>(cfu) 2.74 5, lxl0³ 99.8% 0,19 1,8x10⁶ % 35,6</td>

<td>Method 2</td><td>JIS Japanese Industrial Standard JIS Z 2801: 2000 Antimicrobial products - Test for antimicrobial activity and efficacy. - Plate Count Method -</td>

<td>Test bacteria:</td><td>Escherichia Coli K12</td>

<td>Modification:</td><td>Sample size: 25 mm x 25 mm Calculation: R value only Preincubation C: LB Broth Preincubation D: LB Broth Inoculations-Medium: 1/500 verd. LB Broth (+ 0.13% Tween 80) Incubation: 37 ° C Sample preparation: UVC sterilized</td>

1)% reduction and R value refer to internal standard

Table 2: Determination of anti-mycotic activity for a nano silver coated felt / foil laminate with 150 ppm silver in the coating

one. test result

<td>Control</td><td>Mushroom growth Cat.</td>

<td>Growth control Control, sterility</td><td>Strong 6 No</td>

<td>Samples</td><td>Anti mycotic activity Kat</td>

<td>Cotton (internal standard)</td><td>No 6</td>

<td>Coated felt-foil laminate</td><td>Nano silver apparent 3</td>

<td>2.test method</td><td>SN 195921 - Textile Fabric - Determination of the Antimycotic Activity - Modified</td>

<td>Test bacteria:</td><td>DSM 40464 - Streptomyces abikoensis DSM 9122 - Scopulariopsis brevicaulis DSM 62413 - Fusarium solani DSM 10640 - Penicillium funiculosum DSM 2404 - Aureobasidium pullulans</td>

<td>Modification:</td><td>Sample size: 30 mm 0 Preincubation: Potato Dextrose Agar Suspensions-Medium: Potato Dextrose Bouillon Sample inoculation: Spraying Incubation: 25 ° C, humidity chamber Incubation time: 40 days Sample sterilization: UVC</td>

Example 12:

Use of the inventive formulation to manufacture coatings for textile decor gambling

The nanosilver dispersion from Example 1 is processed in concentrations of 100 mg / kg and 200 mg / kg (with respect to the silver content in the coating) into a fluorine polymer dispersion customary in the market, specified for coating textiles, by means known in the art. A dispersion is obtained from stable, slightly yellow-colored nanosilver particles and fluorine polymer particles. The coating is applied to a textile décor fabric and thermally dried / set / wetted.

Table 3 shows the results of microbiological tests on foot mat decor textiles with 2 different hydrophobic, aqueous coatings and two dosages of nanosilver at a time according to JIS 1902. Hydrophobic, aqueous coatings AG4 and AG8 are the usual fluorine 5 polymer coatings on the market. In the coating AG4, a very strong reduction of bacteria was observed each time against an untreated textile with the aid of a nanosilver additive of 100 mg / kg or 200 mg / kg. An additive of 100 mg / kg of nano-silver in the coating AG8 is not sufficient to inhibit bacterial growth. In contrast, an additive of 200 mg / kg provides a strong reduction of bacteria against a raw textile.

Table 3: Microbiological tests on floor mat decor textiles with 2 different hydrophobic, aqueous coatings and two silver dosages each time according to JIS 1902

one. test result

<td>After 0 hours Vaccine</td><td colspan="2">Average amount of bacteria (cfu) 1.8x10⁵</td>

<td>After 18 hours</td><td>Average bacteria</td><td>F Value</td>

<td></td><td>amount of</td><td></td>

<td>Fiber AO (empty)</td><td>(cfu)</td><td> 1,92</td>

<td></td><td>1,5x10⁷</td><td></td>

Double determination of independent samples

<td>After 18 hours</td><td>Average amount of bacteria</td><td>% reduction 1</td><td>R Value</td>

<td>Control: 080116-xhf01</td><td>(cfu)</td><td></td><td> 5,18</td>

<td>Mesh fabric (Rita), DTY Floor mat decor material</td><td>160 / 200F &lt;1.0x10²</td><td> % 99,9993</td><td> 3,03</td>

<td>coating AG4 100 ppm Floor mat decor material</td><td>1,4x10⁴</td><td> % 99,9</td><td> 1,79</td>

<td>coating AG4 200 ppm Floor mat decor material</td><td>2,4x10⁵</td><td> % 98,4</td><td> -0,49</td>

<td>coating AG 8 100 ppm Floor mat decoration material coating AG8 200 ppm</td><td>4,6x10⁷ No 3.29 7,8x10³ % 99,9</td>

<td>2.test method</td><td>JIS Japanese Industrial Standard JIS L 1902: 2002 Testing for antibacterial activity and efficacy on textile products. - Plate Count Method -</td>

<td>Test bacteria:</td><td>Escherichia Coli K12</td>

<td>Modification:</td><td>Single scale: 0.4 g Calculation: R value only Preincubation C: LB Broth Preincubation D: LB Broth Inoculations-Medium: Phosphate Buffered Saline with 0.05% Tween 80 Incubation: 37 ° C</td>

1)% reduction and R value refer to wasted

Example 13:

Use of the inventive formulation in lacquers and adhesives 5

The nanosilver dispersion from Example 1 is processed into a concentration of 270 mg / kg (as regards the silver content in the finished product) into lacquers suitable for lacquering wood (especially stairs and piece seals) , which are customary in the market as known from the prior art . . Stable dispersions with free nanosilver particles are obtained.

Table 4 shows the results of microbiological tests on water and solvent-based lacquers with 270 ppm nanosilver each time.

The addition of 270 mg / kg nano-silver in both lacquers provides a strong reduction of bacteria compared to standard surfaces.

Table 4: Microbiological tests on water and solvent-based lacquers with 270 ppm nanosilver each time (for ladder and parquet sealing) according to JIS 2801.

<td rowspan="2"> 5</td><td colspan="3">1.test result</td>

<td>After 0 hours Vaccine</td><td colspan="2">Average amount of bacteria (cfu) 2, lxl0⁵</td>

<td></td><td>After 18 hours</td><td>Average bacteria amount of</td><td>F Value</td>

Internal standard (polystyrene) (cfu) 0.02

2,2x10⁵

Double determination of independent samples

<td>After 18 hours Lacquer, water-based, with 270 ppm Ag Lacquer, solvent-based, with 270 ppm Ag</td><td>Average bacteria% reduction R Value amount of ¹(cfu) 3.35 1,0x10² 99.95% 3.35 1,0x10² % 99,95</td>

<td>2.test method</td><td>JIS Japanese Industrial Standard JIS Z 2801: 2000 Antimicrobial products - Test for antimicrobial activity and efficacy. - Plate Count Method -</td>

<td>Test bacteria:</td><td>Escherichia Coli KI2</td>

<td>Modification:</td><td>Sample size: 25 mm x 25 mm Calculation: R value only Preincubation C: LB Broth Preincubation D: LB Broth Inoculations-Medium: 1/500 verd. LB Broth (+ 0.13 % Tween 80) Incubation: 37 ° C Sample preparation: UVC sterilized</td>

1)% reduction and R value refer to internal standard

Example 14:

Use of the formulation according to the invention in silicones

The nanosilver dispersion from Example 1 is processed into conventional silicones as known in the art into typical concentrations of 100 mg / kg to 1000 mg / kg (with respect to the silver content in the finished product). Stable dispersions with free nanosilver particles are obtained.

Table 5 shows the results of microbiological tests on 2-component silicones with different nanosilver contents according to JIS 2802. A further 200 mg / kg nano silver additive provides a strong bacteria reduction of 97.5% compared to standard surfaces. A strong bacteria reduction of 99.9% is provided for 500 mg / kg nano silver.

Table 5: Microbiological tests on 2-component silicones with different nanosilver content according to JIS 2801.

<td colspan="3">1.test result</td>

<td>After 0 hours Vaccine</td><td colspan="2">Average amount of bacteria (cfu) 1.0x10⁵</td>

<td>After 18 hours</td><td>Average bacteria amount of</td><td>F Value</td>

<td>Internal standard (polystyrene)</td><td>(cfu) 1,4x10⁵</td><td> 0,02</td>

Double determination of independent samples

<td>After 18 hours</td><td>Average bacteria% reduction R Value amount of ¹</td>

<td>Silicon with 200 ppm Ag Silicon with 500 ppm Ag Silicon with 1000 ppm Ag</td><td>(cfu) 1.6 3,5x10³ 97.5% 3.1 &lt;1.0x10² 99.9 3.1 &lt;1.0x10² % 99,9</td>

<td>2.test method</td><td>JIS Japanese Industrial Standard JIS Z 2801: 2000 Antimicrobial products - Test for antimicrobial activity and efficacy. - Plate Count Method -</td>

<td>Test bacteria:</td><td>Escherichia Coli K12</td>

<td>Modification:</td><td>Sample size: 25 mm x 25 mm Calculation: R value only Preicubation C: LB Broth Preincubation D: LB Broth Inoculations-Medium: 1/500 verd. LB Broth (+ 0.13 % Tween 80) Incubation: 37 ° C Sample preparation: UVC sterilized</td>

1)% reduction and R value refer to internal standard

Table 15:

Use of the inventive formulation in polypropylene foils

The nanosilver dispersion from Example 1 is extruded into a layer of a multilayer polypropylene foil at typical concentrations between 100 mg / kg and 5000 mg / kg (with respect to the silver content in the finished layer). Foils with predominantly insulated nanosilver particles dispersed homogeneously in a layer of about 5 pm 10 thickness are obtained.

Table 6 shows the results of microbiological tests on multilayer polypropylene foils with different nanosilver contents according to JIS 2801. With 2100 mg / kg or 3200 mg / kg nano-silver, the additive provides a strong bacteria reduction of approximately 99 5% compared to standard surfaces each time.

Table 6: Microbiological tests on a multilayer polypropylene foil.

one. test result

<td>After 0 hours</td><td>Average bacteria amount of</td>

<td>Vaccine</td><td>(cfu) 1.7x10⁵</td>

<td>After 18 hours</td><td>Average bacteria F Value amount of</td>

<td>Internal standard</td><td>(cfu) 0.5 (polystyrene) 5, lxl0⁵</td>

Double determination of independent samples

<td>After 18 hours</td><td>Average bacteria% reduction R Value amount of ¹</td>

<td>Control, antibacterial Foil with 2100 ppm Ag on the inside Foil with 3200 ppm Ag on the inside</td><td>(cfu)&gt; 3.7 &lt;1.0x10² &gt; 99.98% 1.9 5,8x10³ 98.87 1.9% 6,9x10³ 98.66% 1)% reduction and R value, internal</td>

<td>relates to the standard 2.test method</td><td>JIS Japanese Industrial Standard JIS Z 2801: 2000 Antimicrobial products - Test for antimicrobial activity and efficacy. - Plate Count Method -</td>

<td>Test bacteria:</td><td>Escherichia Coli KI2</td>

<td>Modification:</td><td>Sample size: 30 mm x 40 mm Calculation: R value only Preincubation C: LB Medium Inoculations-Medium: 1/500 verd. LB Broth (+0.13% Tween 80)</td>

Incubation: 37 ° C Sample preparation: no

Example 16:

The use of the inventive form la ion in polypropylene liquid containers.

The nanosilver dispersion from Example 1 is processed into a polypropylene by extrusion to a concentration of 6500 mg (with respect to the silver content). Here, a master mixture is obtained with nanosilver particles which are mainly present in isolation from each other. The nanosilver mastermix is ​​processed into polypropylene liquid containers at typical concentrations of 100 mg / kg to 5000 mg / kg with respect to the silver content in the finished polymer. Liquid containers are designated for the collection and intermediate storage of used wash bases or wash solutions from dishwashing or textile washing processes. The addition of nano silver as an additive prevents invasion by bacteria.

Table 7 shows the results of microbiological tests in polypropylene liquid containers with different nanosilver content according to JIS 2801. Addition with 520 mg / kg or 1000 mg / kg or 2000 mg / kg nanosilver provides a strong bacteria reduction of more than 99.99% each time compared to standard surfaces.

Table 7: Microbiological tests on polypropylene liquid containers according to JIS 2801.

one. test result

<td>After 0 hours</td><td>Average bacteria amount of</td>

<td>Vaccine</td><td>(cfu) 3,6x10⁵</td>

<td>After 18 hours</td><td>Average bacteria F Value amount of</td>

<td>Internal standard (polystyrene)</td><td>(cfu) 0.5 Ι, ΙχΙΟ⁶</td>

fold parallel independent determinations

<td>After 18 hours</td><td>Average bacteria% reduction R Value amount of ¹</td>

<td>Control, antibacterial</td><td>(cfu)&gt; 4.0 &lt;1.0x10² % 99,99</td>

<td>Method 2</td><td>J IS Japanese Industrial Standard J İS Z 2801: 2000 Antimicrobial products - Test for antimicrobial activity and efficacy. - Plate Count Method -</td>

<td>Test bacteria:</td><td>Escherichia Coli KI2</td>

<td>Modification:</td><td>Sample size: 30 mm x 40 mm Calculation: R value only Preicubation C: LB Medium Inoculations-Medium: 1/500 verd. LB Broth (+ 0.13% Tween 80) Incubation: 37 ° C Sample preparation: no</td>

1)% reduction and R value refer to internal standard

Example 17:

Use of the formulation according to the invention in Wood Plastic Composites (WPC)

The nanosilver dispersion from Example 1 is mixed in a concentration between 50 mg / kg and 1000 mg / kg during the extrusion of PVC and wood powder. WPC materials resistant to weather conditions and rot are obtained.

Example 18:

The use of the formulation according to the invention in polyolefin form bodies

The nanosilver dispersion from Example 1 is mixed with the aid of white oil with polyolefins (PE or PP) in the form of small polymer beads, such that a silver concentration of 50 mg / kg to 500 mg / kg is obtained in the finished mixture. The mixture is pressed into form bodies (eg cutting boards, filter, cosmetic application tools) in a press and mechanically reprocessed. The resulting cutting boards have an antimicrobial activity with an R-value between 1 and 4, depending on the silver content in each case.

Example 19:

Use of the inventive formulation for the production of PVC Plastisol coated textiles

The nanosilver dispersion from Example 1 is processed into PVC Plastisol at a typical concentration of 400 mg / kg (based on the silver content in the finished polymer). Plastisol is used for coating textile fabrics. For example, mats are obtained that can be used as floor covering in damp places, as gymnastic mats, as a hah stopper or as a dish mat.

The addition of nanosilver as an additive should prevent the invasion of the polymer by microorganisms.

Table 8 shows the results of microbiological tests in polypropylene liquid 5 containers with 400 mg / kg nanosilver additive. The addition of 400 mg / kg of nanosilver as an additive provides significant anti-mycotic activity against the 5 fungi tested.

Table 8: Test for anti-mycotic activity of PVC Plastisol with 400 ppm silver content.

one. test result

<td>Control Cotton (internal standard) Growth control Control, sterility Sample PVC Plastisol washed PVC Plastisol, untreated, with 15 x 400 ppm Ag, 15 x washed 2.test method Test bacteria: Modification:</td><td>Mushroom growth Cat. Strong 6 Strong 6 No Anti mycotic activity Kat Prominent 5 No 3 SN 195921 - Textile Fabric - Determination of the Antimycotic Activity - Modified DSM 40464 - Streptomyces abikoensis DSM 9122 - Scopulariopsis brevicaulis DSM 62413 - Fusarium solani DSM 10640 - Penicillium funiculosum DSM 2404 - Aureobasidium pullulans Sample size: 30 mm 0 Preincubation: Potato Dextrose Agar Suspensions-Medium: Potato Dextrose Bouillon Sample inoculation: Spraying</td>

Incubation: 25 ° C Incubation time: 40 days Sample sterilization: UVC

Example 20:

Use of the inventive formulation in PMMA bone cement

The nanosilver dispersion from Example 1 is processed into conventional PMMA bone cements in the market by means known in the art, in typical concentrations (with respect to the silver content in the finished product) between 100 mg / kg and 5000 mg / kg. The impregnation can be carried out either into dry PMMA powder or into liquid MM A monomer. After freezing, bone cements with a homogeneous distribution of weight-insulated nanosilver particles are obtained.

Table 9 shows the results of the different elution tests. Thus, from table 9, a bone cement test body equipped with 2149 mg / kg was added with 10 ml of SimulatedBodyFluid (SBF) within 12 days in an elution at an elution temperature of 37 ° C.² It appears to lose 4 ng of silver per surface into solution. From the next row in Table 9, it can be seen that slightly increasing the nanosilver content in the test body to 2500 mg / kg and shortening the elution time to 5 days did not provide a significant change in the amount of silver allocated. In an aging experiment, a 13 ng / mm amount was removed by boiling the test body in SBF. A balance of 1.2 ng / mm and days is set in the daily replenishment of the elution fluid.

Table 9: Acrylate bone cement (PMMA) with 2500 ppm Ag

<td></td><td>NAg content in test body</td><td>Elution volume</td><td>Elution temperature</td><td>Elution time</td><td>Leaving silver amount of</td>

<td>Release kinetics</td><td>2149 ppm</td><td>10 mL SBFm</td><td>37 ° C</td><td>12 d</td><td>4 ng / mm (0.4 ng / g mm²)</td>

<td>Silver content variation</td><td>2500 ppm</td><td>10 mL SBFm</td><td>37 ° C</td><td>5 d</td><td>4 ng / mm² (0.4 ng / g * mm)</td>

Example 21:

Use of the inventive formulation to manufacture PMMA coatings

The nanosilver dispersion from Example 1 is processed into commercially conventional PMMA mixtures in a manner known from the prior art 15 at a typical concentration (with respect to the silver content in the finished product) between 100 mg / kg and 5000 mg / kg. The impregnation is carried out either in dry PMMA powder or in liquid MMA monomer. Prepared mixtures are mainly used for coating medical products. After freezing, PMMA 20 coatings with a homogeneous distribution of mainly insulated nanosilver particles are obtained.

Example 22:

Use of the inventive formulation to manufacture synthetic fibers

The nanosilver dispersion from Example 1 is processed into conventional thermoplasts such as polypropylene, polyester, polyamide by extrusion in typical concentrations (with respect to the silver content) between 1000 mg / kg and 20000 mg / kg. Master mixtures are obtained here with nanosilver particles that are present predominantly isolated from each other.

Figure 8 shows a TEM image of a polyester master mix with 6500 mg / kg of silver as an example. The dark spots in Figure 8 show the homogeneous distribution and low agglomeration of the nanosilver particles in the polyester.

Master mixes are used to produce synthetic fibers in thinned form, for example from polypropylene, polyester or polyamide, according to the prior art.

Figure 9 shows multiple microfibre rods of PET / PA with 200 mg / kg nanosilver. In Figure 9, the individual nanosilver particles (open spots) within the segmented spun yarns are clearly visible. Typical silver contents for antimicrobial effects are in the range of 100 mg / kg to 300 mg / kg.

In addition to micro fibers, monofilament and monocomponent fibers for nonwoven material are also manufactured with clothing, mattress pads, cloths and technical textiles. Silver-containing synthetic fibers can also be used to equip other fibers in the form of staple fibers (for example natural fibers such as cotton). The silver contents used are at a higher level compared to direct reinforcement of synthetic fibers by means of other fibers in accordance with the refinement.

Figure 10 shows the elution characteristic (A) and antimicrobial activity (_) of the different polyesters. The silver content of the different fibers lies in the range between 150 mg / kg and 195 mg / kg. The fibers were separated in water for 3 hours each time. The separated silver content ranges from 120 pg / kg to 200 pg / kg of water; antimicrobial blocking is above 96% each time. Table 10 shows the results of the antimicrobial tests of these 5 microfibers according to JIS 1902.

Example 23:

Making a stable dispersion of silver nanoparticles in methyl methacrylate

The product from example 6 or example 7 is used to manufacture a formulation of silver nanoparticles in methylmethacrylate. For this, 990 g of methylmethacrylate (Merck, for synthesis) are placed from the front in a 2 liter beaker and mixed at room temperature on a magnetic stirrer. 1 g of wetting agent (Evonic, Tego disperse 655) is added with a pipette. After the addition of 9.3 g of the product from Example 6, the solution changed color to orange brown. By turning the container, a thin film is created on the glass wall, which is light yellow, clear in color and contains no visible particles. 1,000 g of a dispersion are obtained, which has a silver content of 5.115 mg / kg. Particle size and particle distribution correspond to the illustrations in figure 2 and figure 3.

Example 24:

Making a stable dispersion of silver nanoparticles in methyl methacrylate

The product from example 6 or example 7 is used to manufacture a formulation of silver nanoparticles in methylmethacrylate. For this, 980 g of methylmethacrylate (Merck, for synthesis) are placed from the front in a 2 liter beaker and mixed at room temperature on a magnetic stirrer. 2 g of wetting agent (Evonic, Tego disperse 655) is added with a pipette. After the addition of 18.2 g of the product from Example 6, the solution changed color to orange brown. By turning the container, a thin film is created on the glass wall, which is light yellow, clear in color and contains no visible particles. 1,000 g of a dispersion are obtained, which has a silver content of 10.010 mg / kg. Particle size and particle distribution correspond to the illustrations in figure 2 and figure 3.

Example 25:

Silver in methyl methacrylate¹ Making a stable dispersion from nanoparticles

The product from example 6 or example 7 is used to manufacture a formulation of silver nanoparticles in methylmethacrylate. For this, 897 g of methylmethacrylate (Merck, for synthesis) are placed from the front in a 2 liter beaker and mixed at room temperature on a magnetic stirrer. 10 g of wetting agent (Evonic, Tego disperse 655) is added with a pipette. After the addition of 92.7 g of the product from Example 6, the solution changed color to orange brown. By turning the container, a thin film is created on the glass wall, which is light yellow, clear in color and contains no visible particles. 1,000 g of a dispersion are obtained, which has a silver content of 50,985 mg / kg. Particle size and particle distribution correspond to the illustrations in figure 2 and figure 3.

Example 26:

Manufacturing a PMMA based antibacterial carrier material

The product of example 1 is processed into a PMMA-perlpolymerisate in a concentration between 100 mg / kg and 10,000 mg / kg with respect to the finished product each time. Preferably, the impregnation is carried out in dry PMMA powder. A pharmaceutically effective agent such as Gentamicin, as well as other additives such as zirconium oxide, for example as x-ray contrast agent, can also be added to the PMMA powder.

In the injection molding method, antimicrobial effect spheres with a diameter of between 5 and 10 mm and a weight of between 100 and 300 mg are produced from PMMA powder, for example. This is easily possible due to the heat resistance of the nano silver dispersion up to 240 ° C. A 200 mg sphere contains, for example, 4.5 g of Gentamicin and 20 mg of zirconium oxide.

Spheres can be embedded in a multiple surgical wire.

REFERENCES REFERRED IN THE DESCRIPTION

This list of references cited by the applicant is for the reader's aid only and does not form part of the European Patent Document. Although great attention has been paid to the compilation of the references, errors or omissions cannot be avoided and EPO accepts no liability in this regard.

Patent documents referred to in the description:

DE 102006056284 A1 [00161 * US 2007003603 A1 [00191 • US 2008181931 A1 [0019] JP 2008231489 A [0019]

THE MEANING OF THE ARTICLES IN THE FIGURES

FIGURE 1

A = Suction

B = Wavelength

FIGURE 2

C - Frequency

D = Diameter

FIGURE 5

E = Time (hours)

FIGURE 7

F = Kill

FIGURE 9

G = hire a scientist

FIGURE 10

H = Fiber number

I = Antimicrobial Inhibition

J = Washed Out Silver Content