DE10120802A1 - Process for the production of coated nanoparticles - Google Patents

Abstract

The invention relates to nanoparticles, comprising a support and a coating of a polymer material. The polymer material comprises functional groups, to which reversible metal ions are bonded. Said nanoparticles may be incorporated in plastics and workpieces may be produced from the obtained compounds, which are particularly suitable for medical applications. The workpieces for example, drainage tubes, or inner coatings of medical devices, give off small amounts of metal ions in contact with body fluids which have an anti-microbial or bacteriostatic effect. On longer application the penetration of disease-inducing agents is effectively suppressed.

Description

The invention relates to nanoparticles which are antimicrobial or bacteriostatic Have an effect, a compound that contains these nanoparticles and from which Compound manufactured workpieces. The invention further relates to a method for Production of the nanoparticles, a process for the production of the nanoparticles containing compounds and the use of nanoparticles as an antimicrobial or bacteriostatic agent.

A variety of articles are used for medical needs are made of plastic. Plastics have the advantage that they are easy to put in let any shape shape, are inexpensive to manufacture and if necessary also an increased Flexibility or permeability for e.g. B. may have gases, liquids or ions. Many of these items are made for single use and then discarded. The objects are z. B. by Fumigation sterilized with ethylene oxide and then packaged sterile. If necessary, the The package is torn open and the item can be removed sterile. For a long time Use, e.g. B. after as a drainage hose for draining tissue fluids Operations or as a splint, which is inserted into the ureter, for example However, there is a colonization with germs, which pose an infection risk for the Represents patient. It is therefore endeavored to design such objects in such a way that A sterility or at least a considerable reduction even with prolonged use the number of bacteria is guaranteed. The germicidal effect of metal ions has been around known for a long time. For example, handrails or handles made of brass are not made by Germs colonized and are therefore particularly suitable for use, for example, in  public buildings. Another metal that also has a germicidal effect is silver. Silver calls in the human body even after prolonged contact low doses do not produce any negative reactions. One has therefore tried to Plastics silver compounds to store, so that the plastic objects over to be able to keep a germ free for a longer period. The production of such plastics encounters difficulties, however, because the silver salts are easily reduced and one Train the silver mirror. The silver salts are therefore difficult to evenly Plastic distributes and separates during the manufacture of the Plastic objects easily in the equipment used to manufacture or on from the surface and inside of the plastic objects and lead to discoloration. The silver concentration in the plastic objects is usually low and fluctuates within a production line. This makes it difficult to plastic objects produce the reproducible under physiological conditions over a longer period Period of time to release a sufficient amount of silver ions to reliably a ensure germicidal effect.

EP 0 655 002 B1 describes a method for producing a non-germ and / or fungi populated plastic part described. This is the plastic first pretreated with a swelling agent and the swollen plastic obtained with a solution of a water-insoluble compound that is a bactericidal and / or contains fungicidal metal. There are different metal salts proposed, with silver salts being preferred.

Although a germicidal effect is described in this document, there is still one considerable space for developments through which the manufacture of such plastics is simplified. In particular, the difficulties caused by the easy reducibility caused by silver salts. Furthermore, the should Workpieces made of such plastics over a longer period of time a sufficient amount of silver ions, especially under physiological conditions can give up in order to develop a germicidal effect.

The object of the invention is therefore to provide a means that is easy in Materials, especially plastics, can be incorporated to the materials to give a germicidal effect. This means should also be such that the material lasts for a long time, especially under physiological conditions releases a sufficient amount of metal ions to kill germs.

The object is achieved by nanoparticles comprising a carrier and a carrier surrounding coating, which contains functional groups that act as proton donor or Electron donors act, whereby at least part of the functional groups Metal ions are bound.

Nanoparticles are spherical, rod-like or platelet-shaped particles that run along their longest extension generally a diameter of at most 500 microns exhibit. They can simply be put in as dry powder or in the form of a suspension Incorporate different materials, incorporating in for the invention The focus is on plastics. The nanoparticles according to the invention have one multilayer structure, the carrier having a core with high mechanical Stability forms, which is surrounded by a coating. Through the functional groups of the Coatings are reversibly bound to metal ions and can be removed from liquids such as Body fluids, from which nanoparticles are released. Binding the Metal ions can be done in any way per se, provided that the Metal ions through liquids is possible. For example, the metal ions be bound ionically by the coating having anionic groups which have a have a sufficiently strong binding effect on the metal ions. Are suitable for this for example carboxyl groups or hydroxyl groups. Furthermore, e.g. B. a binding of Metal ions possible in the form of a complex. This happens particularly advantageously when chelate-like functional groups are provided in the coating.

Nanoparticles with a defined particle size can be produced by the carrier be, for example, free-flowing and easily in plastic materials  have it incorporated. It was found that although the nanoparticles in the Polymer matrix of the plastic are included, yet metal ions from the Nanoparticles can be released into the environment. Probably part of the Nanoparticles on or near the surface of a plastic compound manufactured workpiece and releases metal ions to the environment. Can also Plastics swell under physiological conditions, so that they also deeper Areas of the plastic compound metal ions are supplied to the surface. A large variety of compounds can be used as a coating, whereby in particular polymers are preferred which have a good binding action for metal ions exhibit. The mechanical properties are those used for the coating Polymers of minor importance because of the mechanical strength of the Nanoparticles is guaranteed by the carrier.

The coating must have a sufficient binding effect for metal ions. Compounds which have functional groups which can bind metal ions are therefore particularly suitable for the coating. The groups can be provided at any point on the molecular structure. Functional groups which are selected from a group which is formed from -COOH, -COO-, -CON-, -CONH-, -CONH ₂ , -SH, -SOH, -SO ₂ H, -SO _{3 are} particularly suitable H, -S-, -SO-, -SO ₂ -, -NH ₂ , -NOH, -NO ₂ H, -NH-, -NO-, -OH, -O-, -SiOH, -Si (OH) ₂ , -Si (OH) ₃ , -SiO-, -Si (O-) ₂ , -Si (O-) ₃ , -PH-, -PH ₂ -, -PO-, -POH-, -POH ₂ , -PO ₂ -, -PO ₂ H-, -PO ₂ H ₂ , -PO ₃ -, -PO ₃ H-, -PO ₃ H ₂ , -PO ₄ -, -PO ₄ H, -PO ₄ H ₂ .

Examples of compounds with such functional groups are polyacrylic acid, Polyacrylamide and copolymers of acrylic acid and acrylic acid amide, phosphates, Ethylenediaminetetraacetate, ethoxylates, propoxylates, N-vinylpyrrolidone, etc.

The compounds from which the coating is formed can be selected from a large number of compounds. Monomers with a molecular weight of up to approx. 300 g / mol, oligomers with a molecular weight of 300 to 3000 g / mol or polymers with higher molecular weights can be used. The coating is particularly suitably formed by a polymer which has a molecular weight of 100 to 10 ⁷ , preferably 500 to 10 ⁷ g / mol. Such polymers can be drawn onto a carrier and form a sufficiently stable connection to the surface of the carrier. This means that there is no danger that the coating will come loose from the wearer after a long period of use. Furthermore, the nanoparticle shows sufficient mechanical resistance so that it can be worked into a polymer matrix using an extruder, for example.

Good adhesion to the carrier and a good binding effect, for example, show nitrogen-containing polymers, such as polyalkylene polyamines. The amino group can both be included in the chain of the polymer, e.g. B. as a secondary amine group, such as also in a side chain. The amino group has one with the lone pair of electrons Binding point for the metal ion, so that the metal ion is sufficiently strong in the coating is bound. An exemplary polyalkylene polyamine is polyvinylamine.

A class of nitrogen-containing polymers, which are particularly suitable as coatings, are polyalkylene polyimines. Polyalkyleneimines, such as polyethyleneimine, have bad ones mechanical properties and are therefore for the production of articles for the not suitable for medical needs. However, the polyimines are suitable Carrier material, which itself forms a nanoparticle in the sense of the invention, applied, an easy-to-use material is created that forms a composite with plastics can be processed.

The polyalkylene polyimine preferably has a structure of the formula I.

where R ¹ , R ² , R ³ , R ^{4 are} independently:
-H, an alkyl group having 1 to 10 carbon atoms, an aryl group having 5 to 20 carbon atoms or an aralkyl group having 6 to 20 carbon atoms;
A, B independently of one another:
- (CR ⁵ R ⁶ ) -, -C (O) -O-, -C (O) -, -C (O) -N (R ⁵ ) -, -S-, -S (O) -, - S (O) ₂ -, -N (R ⁵ ) -, -O-, -Si (R ⁷ R ⁸ ) -O-, -P (R ⁵ ) -, -P (O) -, -P (OH ) -, -P (O) ₂ -, -P (O) (OH) -, -P (O) (OH) -O-, -OP (O) ₂ -O-,
where A and B can be arranged in any order;
C: -H, -CH ₃ , -COOH, -CONH ₂ , -SH, -SOH, -SO ₂ H, -SO ₃ H, -NH ₂ , -NHOH, -OH, -SiH ₂ OH, -SiH ( OH) ₂ , -Si (OH) ₃ , -PH ₂ , -P (O) H ₂ , -PH (O) OH, -P (O) (OH) ₂ , -O-, P (O) (OH ) ₂ ;
R ⁵ , R ⁶ : independently of one another H, an alkyl group having 1 to 10 carbon atoms;
R ⁷ , R ⁸ : R ⁵ , R ⁶ , OR ⁵ , OR ⁶ ;
m: an integer between 0 and 10;
n: an integer between 0 and 10;
o: an integer between 0 and 1000;
x: an integer between 0 and 10 ⁷ ;
y: an integer between 0 and 10 ⁷ ;
where x + y ≧ 1;
E: a common end group;
R ⁹ , R ¹⁰ : -H, - (A _m B _n ) _o -C.

The structure of the end group E results from the production of the polyimines. in the In general, E is a hydrogen.

If the polyalkylene polyimine has further structural units of the formula II,

in which R ¹ and R ^{2 have} the meaning given in claim 6 and z is an integer between 0 and 10 ⁷ , branching points are formed in the polyalkylene polyimine. The polymer chain is then continued via both nitrogen binding sites, which are denoted by * in formula II. Polyalkylene polyimines of different degrees of branching and different molecular weights can be used. The proportion of secondary nitrogen atoms (2 ° N) is a measure of the degree of branching. There are z. B. unbranched polyethyleneimines with 2 ° N = 99% via (partially) branched polyethyleneimines up to polyethyleneimines with dendrimeric structures with 2 ° N = 0. Preferred are polyethyleneimines with a content of secondary nitrogen atoms of 20 to 60%.

The polyalkylene polyamines can be reacted with reactive compounds be modified. Compounds containing reactive groups, such as Carboxyl groups, glycidyl groups, epoxy groups, isocyanato groups, aldehyde groups, Contain halogens or activated double bonds.

The polyalkylene polyamines used as coatings can also be crosslinked. Coming all known crosslinkers are taken into account. Halogen-containing crosslinkers are an example such as (poly) alkylene polyhalides, especially 1,2-dichloroethane, and in particular  Epichlorohydrin and its reaction products with polyalkylene glycols (Polyalkylene glycol bisglycidyl ether), especially ethylene glycols.

Other suitable bifunctional, halogen-free crosslinkers are e.g. B. in DE-A 196 07 641 Substances described: alkylene carbonate, urea; monoethylenically unsaturated Carboxylic acids, at least dibasic saturated carboxylic acids or polycarboxylic acids and their esters, amides and anhydrides; Reaction products of polyether diamines, Alkylenediamines, polyalkylene polyamines, (poly) alkylene glycols and mixtures thereof with monoethylenically unsaturated carboxylic acids, esters, amides and anhydrides, where the reaction products have at least two ethylenically unsaturated double bonds, Contain carboxamide, carboxyl or ester groups as functional groups; such as reaction products of at least two aziridino groups Dicarboxylic acid esters with ethyleneimine.

In the nanoparticles according to the invention, a weight ratio of Carrier for coating from 1000: 1 to 1:10, preferably 10: 1 to 1: 1, selected.

The carrier is preferably formed from an inorganic material. By the the nanoparticle receives sufficient strength and an inorganic material adequate chemical resistance. Such particles can also be used with produce a very large surface area, which is used to absorb metal ions Available area can be enlarged. This allows the amount to be advantageous increase the metal ions absorbed by the coating. Furthermore, the later application, for example in an article for medical needs, the It is also easier to detach the metal ion from the coating material, which means that the Available amount of metal ions can be increased.

The inorganic material is preferably selected from a group that is formed from Ag, Au, Ni, Pd, Pt, Cr, Cu, Co, Rh, Ru, Ti, Sn, Al and their oxides. The carrier leaves  produce by known methods, for example by reducing the corresponding metal salts or by a sol-gel process by hydrolysis organic esters of metal acids, whereby metal oxide nanoparticles are obtained. The average particle size of the metal oxide particles or metal particles is generally 10 up to 500 nm, preferably at 20 to 100 nm.

SiO ₂ is preferably used as the inorganic material. Silica gel is available on the market in a suitable grain size.

SiO ₂ which has been generated in situ is particularly preferably used. This means that the SiO _{2 is produced} in the presence of a compound which forms the coating by alkaline hydrolysis of tetraalkoxysilanes. Such a method is described in DE 198 21 665 A1. This produces an SiO ₂ with a very large surface area, which is particularly suitable for loading with a polymer. The particle size of the SiO ₂ particles is influenced by the molecular weight of the preparation by the sol-gel process in the presence of the polyamine and can therefore be directed in the desired direction. Is the molecular weight of polyethylene polyimine z. B. about 2000 g / mol, there are usually SiO ₂ primary particle sizes of about 200 to 500 nm, while with a molecular weight of the polyethyleneimine of about 2,000,000 SiO ₂ primary particle sizes of generally 10 to 50 nm result. In particular with nanoparticles that have a carrier that has been generated in situ, sufficient concentrations of metal ions can be achieved for a germicidal effect.

The nanoparticles according to the invention can be any metal ions or metals bound included. For use in particles for medical needs however, the bound metal ions advantageously have antimicrobial metal ions. The Metal ion is preferably selected from a group which is formed from silver, Copper, gold, zinc or cerium ions, with Ag (I) ions being particularly preferred.  

In order to achieve a sufficient distribution in the polymer matrix, this shows Nanoparticles preferably have a diameter of 1 along their longest dimension to 1000 nm, preferably 1 to 500 nm.

In order to achieve a sufficient germicidal effect, the nanoparticle exhibits based on the weight, preferably a proportion of metal ions, calculated as metal, from 0.02 to 5%, preferably 0.1 to 3%.

As already mentioned, the nanoparticles according to the invention can be very easily in Incorporate plastics, which thereby get germicidal properties. The invention therefore also relates to a compound comprising a polymer matrix, in which the nanoparticles described above are embedded. With the compound stands a material is available that can be processed into a variety of articles and whose properties can be varied over a wide range by the Polymer matrix is modified accordingly.

According to a preferred embodiment, the polymer matrix is made from a thermoplastic or a thermosetting plastic.

The thermoplastic is preferably selected from a group which is made of polyethylene, polypropylene, polystyrene, polyurethane, polyester, Polyamide, and silicones. The thermoplastics can be both individually as well as used in a mixture with each other.

The thermosetting plastic is preferably selected from a group that is formed from urea-formaldehyde resins, melamine-formaldehyde hearts, urea Glyoxalharzen. These plastics can be used individually or in combination use with each other.  

In addition to the compounds mentioned, the compound according to the invention can also be used Contain conventional additives, such as plasticizers, fillers or pigments.

Another object of the invention is a method for producing the above described nanoparticles. For this purpose, a carrier is coated with a coating which contains functional groups that act as proton donors or electron donors, while receiving a coated carrier. The coated carrier is then with Load metal ions.

According to a preferred embodiment, the carrier is in a solvent suspended, the coating dissolved in the solvent and the carrier with the coating coated. Different variations of this method can be carried out. For example, the carrier can be suspended in a solvent and that Coating can also be dissolved separately in the solvent. The suspension and the Solution are then combined to coat the support. It is the same possible to first dissolve the coating in the solvent and then the carrier to the solution admit.

According to a particularly preferred embodiment, the carrier is in situ in the presence of the dissolved coating. As mentioned above, the carrier can be alkaline Hydrolysis of the esters of the corresponding metal acids are generated. The coating can already exist as a polymer. But it is also possible to coat monomers add and the coating during the coating by polymerizing the To produce monomers. A corresponding manufacturing process is in DE 198 21 665 A1 described. The loading of the coated carrier is generally so performed that the coated carrier in a solution of the metal ion in a suitable Is given solvent and then with stirring at a suitable temperature and at a suitable pH, the coated carrier is loaded with the metal ions.  

According to a special embodiment of the method, the metal ions can can also be added while the support is being coated with the coating.

The solvents are suitably selected from a group formed from Water, alcohols and their mixtures. Examples of alcohols are methanol, Suitable for ethanol or propanol. Suitable mixing ratios can be from Easily determine a specialist through appropriate preliminary tests.

The coated carrier can also be loaded in a two-phase system. The coated carrier is suspended in a first solvent, as is the Metal ions dissolved in a second solvent, which in the first solvent Is essentially immiscible, so that a two-phase system is formed. To the The coated ions are loaded from the second solvent into the coated carrier first solvent transferred.

As already explained above, the nanoparticles according to the invention can be used Produce compounds that have beneficial properties, such as a germicide Effect. The invention therefore also relates to a method for producing the above described compounds. The nanoparticles described above are divided into one Plastic introduced. As plastics, for example, those mentioned above can be used thermoplastics or thermosetting plastics can be used.

The nanoparticles can be made into thermoplastics by known methods incorporated. For example, mechanical incorporation of the nanoparticles is suitable in the thermoplastics. This can be done, for example, in a kneader, an extruder, or a roller mill. Suitable methods of compounding are Known specialist.  

In the case of thermosetting plastics, the nanoparticles can, for example, by Copolymerization can be reacted into the plastic during resin condensation.

According to a further embodiment of the method according to the invention, a Suspension of the nanoparticles generated in a solvent, the suspension with the Plastic, which can optionally be diluted with the solvent, combined to obtain a mixture from which the solvent is then removed.

The solvent is chosen depending on the plastic used. To one To achieve even distribution of the nanoparticles in the plastic, the plastic should be soluble in the solvent. After creating a mix in which the Nanoparticles are suspended in a solution of the plastic, the solvent removed by usual methods. Generally the solvent is distilled off due to the lower temperature load even under reduced pressure can be worked.

According to a particularly advantageous embodiment, the nanoparticles are under Exposure to ultrasound suspended. It becomes a very finely divided suspension obtained, and the nanoparticles expose themselves more slowly within the polymer mixture the suspension, so that a homogeneous distribution of the nanoparticles in the plastic is guaranteed.

The nanoparticles settle out of the suspension following gravity. Becomes a Workpiece produced by, for example, a suspension of nanoparticles, Plastic and solvent poured into a mold and then the solvent is usually removed, a workpiece with an irregular distribution of the Nanoparticles. While the side in the mold below is tight with nanoparticles is occupied, the opposite, upper surface is almost free of nanoparticles. The The solvent must therefore be removed so quickly that the nanoparticles in the  Have not yet sold essentially. When removing the solvent therefore advantageously proceeded in such a way that a first part of the solvent quickly is removed from the mixture to an extent that the viscosity of the mixture is increased to such an extent that the nanoparticles essentially no longer sink. The remaining solvent is then removed. This can be essential slower speed. Rapid removal of the solvent can for example in a hot air stream or by distillation under reduced pressure respectively. During the rapid removal of the solvent, exposure to Ultrasound on the suspension continued to further the nanoparticles To stay in balance. Due to the increased viscosity of the mixture, the nanoparticles kept in suspension so that an even distribution of the nanoparticles in the Material can be achieved. Has the viscosity of the mixture of plastic Solvents and nanoparticles increased to such an extent that the nanoparticles essentially no longer decrease, the rate at which the solvent is removed be significantly reduced. This will prevent the surface of the Workpiece becomes irregular, for example due to bubbles or cracks.

A temperature of at most is advantageous when the solvent is evaporated 80 ° C, preferably at most 50 ° C, not exceeded. Within this Temperature ranges, the thermal load on the plastic is still low. metal ions can have a catalytic effect and cleavage of bonds in the Effect polymers. This leads to decomposition of the polymer. Furthermore, too some of the metals, such as silver ions, are slightly reduced to what metal also to decompose the polymer and to deposit the metals and thus can lead to discoloration of the plastic. Are the specified temperatures not exceeded, such processes do not occur to any significant extent.

According to a further advantageous embodiment of the method according to the invention the compound is produced by first of all a coated carrier which is obtained by coating a support with a coating which contains functional groups contains, which act as proton donors or as electron donors, in a  Polymer matrix is introduced, the polymer matrix with the introduced coated If necessary, the carrier is formed into a shape, and the coated carrier is subsequently formed is loaded with metal ions.

According to this embodiment of the method, the coated carrier is in unloaded condition, d. H. without first storing metal ions in the coating were introduced into the polymer matrix. This has the advantage that the polymer matrix with the coated carrier has a much higher temperature stability than one Polymer matrix in which nanoparticles have been introduced that already contain metal ions are loaded. This makes the material much easier to process, extrude, for example, since there are no problems with thermal discoloration Stress, for example during extrusion, can be observed. The The finished workpiece can then be loaded with metal ions. Surprisingly, the coated ones embedded in the polymer matrix can Carrier particles still absorb a sufficient amount of metal ions so that over a long-term germicidal effect can be achieved.

As already explained above, from the compound according to the invention Workpieces with advantageous properties can be produced. Subject of the invention is therefore also a workpiece consisting of the invention described above Compound. The workpieces have a germicidal effect and can therefore be produce advantageously in the form of articles for medical needs, such as for example hoses or linings of lines or other cavities, which must be kept sterile over a longer period of time and for which the There is a risk of contamination with germs.

Another object of the invention is the use of those described above Nanoparticles as an antimicrobial or bacteriostatic agent.  

The invention is illustrated by examples and with reference to the accompanying Figures explained in more detail. It shows

. Figure 1 shows a measurement curve, in which the change of the pH value is applied a silver salt solution in the absorption of the silver ions to coated nanoparticles versus the amount of added silver ions;

Fig. 2 is a plot, in which the pH value and the amount of free silver ions is plotted against the amount of silver ions which is added to a suspension of coated nanoparticles;

Fig. 3 is a plot of silver ion release at successive HNO ₃ addition;

Fig. 4 temperature gravimetry curves of the silver-free sample (a) and a curve after silver detachment (b).

example 1 Representation of modified silicon dioxide nanoparticles with polyethyleneimine after Sol-gel process

The nanoparticles were produced analogously to that in DE 198 21 665 A1 described method.

A mixture of 89 g aqueous ammonia (25% by weight), 571.2 g water and 571.2 g aqueous ethanol (96% by weight) are heated to 50 ° C. with stirring. It'll be first 121.44 g of tetraethoxysilane (98%) and then a mixture heated to 40 ° C.  13.38 g aqueous polyethyleneimine solution (22.2% by weight) and 311.04 g ethanol quickly added. The suspension is stirred at 50 ° C for 5 hours.

After cooling to room temperature, the modified with polyethyleneimine The nanoparticles are filtered off and washed several times with water. The drying takes place over several days at 80 ° C in a drying cabinet.

A white, free-flowing powder was obtained.

Example 2 Representation of silicon dioxide nanoparticles modified with polyethyleneimine after a Variation of the sol-gel process

A mixture of 89 g aqueous ammonia (25% by weight), 571.2 g water and 571.2 g aqueous ethanol (96% by weight) are heated to 50 ° C. with stirring. For this, a mixture of 13.38 g of aqueous polyethyleneimine solution (22.2% by weight) heated to 40 ° C. and 311.04 g of ethanol were added. 121.44 g of tetraethoxysilane (98%) added. The suspension is stirred at 50 ° C for 5 hours.

After cooling to room temperature, the SiO ₂ nanoparticles modified with polyethyleneimine are filtered off and washed several times with water. Drying takes place in a drying cabinet at 80 ° C for several days.

A white, free-flowing powder was obtained, which compared to that in Example 1 obtained powder has higher polymer content.  

Example 3 Representation of silica nanoparticles modified with polyethyleneimine

A mixture of 89 g of aqueous ammonia (25% by weight), 571.2 g of water and 571.2 g of aqueous ethanol (96% by weight) are heated to 50 ° C. with stirring. For this purpose, a mixture of 13.38 g aqueous polyethyleneimine solution (22.2% by weight) and 311.04 g ethanol heated to 40 ° C. is added. After homogenization, 121.44 g Si (OEt) ₄ (98%) is added over 8 hours. The suspension is stirred at 50 ° C. overnight. After filtration, it is washed several times with water. Drying takes place in a drying cabinet at 80 ° C for several days.

A white, free-flowing powder was obtained.

Example 4 Representation of modified silicon dioxide nanoparticles

A mixture of 22.25 g aqueous ammonia (25% by weight), 142.8 g water and 142.8 g aqueous ethanol (96% by weight) are heated to 50 ° C. with stirring. Then be 30.36 g tetraethoxysilane (98%) added. 12.43 g carboxymethylated polyimine (Lupasol® anhydrous, BASF AG, Ludwigshafen) are made up to 24.91 g with water and 77.76 g of ethanol were added. This forms an emulsion. This quickly becomes ammoniacal solution of tetraethoxysilane. The suspension is used for 5 Stirred at 50 ° C for hours and then cooled to room temperature. The precipitation will filtered off and washed several times with water. The drying takes several days at 80 ° C in a drying cabinet.  

A white, free-flowing powder was obtained. Compared to that in Example 1 The powder obtained is the powder obtained in Example 4 significantly finer and softer.

Example 5 Representation of modified silicon dioxide nanoparticles with a coating Polyethyleneimine which is amidated with 60 mol% lauric acid

A mixture of 22.25 g of aqueous ammonia (25% by weight), 142.8 g of water and 142.8 g of aqueous ethanol (96% by weight) are heated to 70 ° C. with stirring. Then 30.36 g of tetraethoxysilane (98%) are added. 11.84 g of a melted polyimine, which is amidated with 60 mol% lauric acid, are made up to 53.82 g with water at 70 ° C. and 77.76 g of ethanol at 70 ° C. are added, an emulsion being formed. This is quickly added to the ammoniacal solution of the tetraethoxysilane. The suspension is stirred for 5 hours at 70 ° C and then cooled to room temperature. The precipitate is filtered off and washed several times with hot water at 60 ° C. Drying takes place over several days at 50 ° C in the drying cabinet and then overnight with the help of P ₂ O ₅ on the oil pump.

A slightly yellow, free-flowing powder was obtained.

Example 6 Representation of modified silicon dioxide nanoparticles starting from silica gel (0.04- 0.063 mm) with a coating of polyethyleneimine, which with 15 mol.% Stearic acid is amidated

A mixture of 22.25 g aqueous ammonia (25% by weight), 142.8 g water and 142.8 g aqueous ethanol (96% by weight) are heated to 40 ° C. with stirring. After encore 8.96 g of silica gel (0.04 to 0.063 mm) becomes a 40 ° C warm emulsion of 3.34 g of a melted polyimine which is amidated with 15 mol.% stearic acid in 11.89 g water and 77.54 g ethanol added. The suspension is left for 5 hours Stirred at 40 ° C. The precipitate is then filtered off with warm water washed and dried on the oil pump at room temperature.

A white, free-flowing powder was obtained, which consists of spherical particles.

The proportion of polyethyleneimine on the silicon dioxide nanoparticles was in each case determined thermogravimetrically. The results are shown in Table 1.

Table 1

Thermogravimetrically determined polyethyleneimine content on the silicon dioxide nanoparticles

Example 7 Covering of the silicon dioxide nanoparticles modified with polyethyleneimine silver ions

45.03 g of the silicon dioxide nanoparticles coated with polyethyleneimine are finely ground and suspended in 750 ml of water under nitrogen. 25 ml of a solution of 5.948 g of AgNO ₃ in 50 ml of water are added to this solution. The suspension is stirred for 5 hours and then the precipitate is filtered off on a Buchner funnel. The residue is washed with distilled water until silver detection with Cl ^{- is} negative. Drying takes place under reduced pressure at 50 ° C in the drying cabinet.

Example 8 Determination of the change in pH during the binding of silver ions to the polymers

2 g of the silicon dioxide nanoparticles coated with polyethyleneimine are suspended in 200 ml of water and 5 ml of 0.1 M NaNO ₃ as a conducting electrolyte for a constant ionic strength (ISA). For this, a highly diluted aqueous silver nitrate solution (0.05 mol / l) is added in 200 µl steps. The pH value is registered every 120 s and plotted against the amount of silver. To measure the curve shape of pure polyethyleneimine, 912.3 mg of anhydrous polyimine were dissolved in 200 ml of water and examined analogously. The results are shown in Fig. 1. Curve (a) shows the change in pH for pure polyethyleneimine, curve (b) shows the course for SiO ₂ nanoparticles which are coated with about 35% by weight of polyethyleneimine, and curve (c) shows the course for SiO ₂ -Particles that are coated with about 26 wt .-% polyethyleneimine.

The coated nanoparticles with the higher polyethyleneimine content (curve (b)) show at the start of the measurement, a higher pH than the nanoparticles with a lower one Polyethyleneimine content (curve (c)). The pH approaches at higher Polyethyleneimine also asymptotically at a higher pH than that of the Nanoparticles with a lower proportion of polyethyleneimine. With pure polyethyleneimine (Curve (a)), silver is also coordinated, but the pH hardly drops. at The coated nanoparticles bind the silver ions with elimination  of a proton, while with free polyethyleneimine the degree of metal ion binding can be controlled by the p-H value.

Example 9 Determination of the pH value and the amount of free silver ions

253.9 mg of the silicon dioxide nanoparticles modified with polyethyleneimine are suspended in 50 ml of water and 5 ml of 2 M KNO ₃ (ISA). A silver sensitive electrode is used to detect silver. 50 µl of a 0.1 M AgNO ₃ solution is added every 300 s after the measurement values have been recorded. The pH and the amount of free silver ions are plotted against the amount of silver ion added. The curves are shown in Fig. 2.

Example 10 Measurement of the equilibrium between H ⁺ and Ag ⁺ ions

0.4 ml of 0.1 M AgNO _{3 are} rapidly added to 236.4 mg of silicon dioxide nanoparticles modified with polyethyleneimine in 50 ml of water and 5 ml of 2 M KNO ₃ (ISA). The pH and the amount of free silver ions are initially registered every 5 s, later at intervals of 30 s, 60 s, 120 s and 300 s. The measurement is continued for approx. 8 hours. The pH value and the silver ion concentration are plotted against time and the two measurement curves, pH value and silver ion concentration are plotted against one another on a dual analog recorder.

Example 11 Production of Ag solutions (test solutions) by removing Ag ⁺ from the modified silicon dioxide nanoparticles coated with polyethyleneimine

4 g of the silicon nanoparticles loaded with silver ions are taken up in 50 ml of water under nitrogen. For this, 20 ml of diluted HNO _{3 are} added. The suspension is stirred for 2 hours. After filtration through a Buchner funnel, it is washed with about 20 ml of water. The filtrate is transferred quantitatively to a 250 ml volumetric flask and supplemented with water to the mark (test solution).

Example 11.1 Determination of the silver according to Vollhard

50 ml of test solution from Example 11 are mixed with 3 ml of an indicator solution containing Fe ³⁺ and diluted to about 100 ml with water. Titrate with 0.1 M NH ₄ SCN standard solution while stirring until a weak red color remains. 1 ml ammonium thiocyanate solution (0.1 M) corresponds to 10.7868 mg Ag.

Example 11.2 Determination of the silver with a silver sensitive electrode

50 ml of the silver-containing test solution from Example 11 are mixed with 5 ml of 2 M KNO ₃ (ISA) and measured.

The values measured in Examples 11.1 and 11.2 are in Table 2 summarized.

Example 12 Silver determination with successive addition of acid

2 g of the silicon dioxide nanoparticles loaded with silver ions are taken up in 50 ml of water and 5 ml of 2 M KNO ₃ (ISA). 1 M HNO ₃ or dilute HBF ₄ (0.8 M) is added in 0.2 ml steps. The amount of free silver ions is recorded with a silver-sensitive electrode and plotted against the added amount of HNO ₃ . The process is continued until there is no change in the measured value when HNO ₃ is added again. The measurement curve is shown in FIG. 3.

The course of the curve shows an initialization phase of up to approx. 0.8 ml 1 M HNO ₃ , in which the silver ion concentration increases only slightly. This is followed by a steep increase in the concentration of free silver ions, which briefly flattens between 4 and 6 ml and then rises again and reaches a maximum end value. The flattening of the curve indicates a buffer system.

Example 13 Investigation of possible chemical changes in the polyethyleneimine after Silberadsorption

4 g of the silicon dioxide nanoparticles loaded with silver ions are mixed in 50 ml of water with 5 ml of smoked 65% HNO ₃ and stirred under nitrogen for 2 hours. The filter residue is filtered off, dried at 50 ° C and examined thermogravimetrically. The result is compared with the silver-free analogues, ie the unloaded coated carrier. The measurement curves are shown in FIG. 4. Curve (a) shows the curve for silver-free modified SiO ₂ nanoparticles and curve (b) the curve for SiO ₂ nanoparticles, which were initially coated with silver ions, the silver then being removed again.

Example 14 Production of polyurethane films

150 mg of coated silicon dioxide nanoparticles loaded with silver ions are dissolved in 2 ml Given DMF and treated with ultrasound under ice cooling until only extremely fine Particles are present. This suspension is added to 10 g of base polymer, which consists of a solution of 100 g polyurethane in 700 g DMF. After homogenization by mechanical stirring, the suspension is brought into a form previously heated to 50 ° C cast. The main part of the solvent is evaporated with a hot air dryer until the viscosity of the mass has increased significantly and has become a honey-like, hardly has solidified more flowable mass. The mold is transferred to a drying cabinet where it is dried for a further 5 days at 50 ° C. Remaining DMF is spread over several Days removed in a high vacuum.

Example 15 Production of a polyurethane strand on the micro-compounder

2.025 g of polyurethane are fed to the extrusion screws within 90 s. The Device temperature is 220 ° C, the speed of rotation of the extrusion screws 100 rpm. Subsequently, 0.45 g of silver ion-loaded is added coated silicon dioxide nanoparticles and a further 2.025 g of polyurethane. The The strand of polyurethane is drained onto an aluminum sheet and to room temperature cooled. A brown to black polyurethane strand was obtained.

Example 16 Subsequent covering of a polyurethane strand, which is silver-free with polyethyleneimine contains coated silicon dioxide nanoparticles

A strand of polyurethane was produced analogously to Example 15, but coated Nanoparticles were added that had not yet been loaded with silver ions.  

300 mg of the polyurethane strand are placed in a two-necked flask in 50 ml of silver nitrate solution and stirred. The silver nitrate solution is obtained in the following manner. First, a stock solution is prepared by adding 788.4 mg AgNO ₃ and 20 ml 0.1 M HNO ₃ to 250 ml with distilled water. A dilution 1 is prepared with this stock solution by adding 50 ml of the stock solution and 5 ml of 2 M KNO ₃ (ISA) to 100 ml with distilled water. Dilution 1 is used to prepare a dilution 2 by diluting 5 ml of dilution 1 and 5 ml of 2 M KNO ₃ (ISA) to 100 ml with distilled water. The silver solution obtained as dilution 2 is used for the coating of the PU strand. The silver nitrate solution has an Ag ⁺ concentration of approx. 50 mg / l. The Ag ⁺ ions remaining in the solution are determined in the dark. Immediately after the silver nitrate standard comes into contact with the polyurethane strand, the electrodes are immersed in the solution, the glass bulb is sealed as far as possible and a measurement value is recorded every 20 minutes. The concentration of free silver ions is plotted against time.

After completion of the measurement, the electron drift is checked by again producing several standard solutions from the stock solution and comparing the standard values with the measured values. The curve obtained is shown in FIG. 1. The decrease in the free silver ions in the solution over a period of 24 h can clearly be seen. The amount of silver taken up can be determined quantitatively at 0.2% by weight, based on the polyurethane test specimen. A silver deposit or a filling of silver salts could not be observed.

Example 17 Biological tests General working instructions

The material to be examined was 60 min. with Staphyloccocus Epidermidis O-47 Incubated at 37 ° C. The samples are then transferred to a nutrient-poor environment, in  which the more or less vital daughter cells are now released. Subsequently, full medium, i. H. nutrient-rich substrate, fed and the number of vital cells or the rate of proliferation. This happens through Record the turbidity, which is determined by measuring the optical density at 578 nm can be tracked. If this increases, i. H. if growth occurs, this is shown by a rising curve, if there is no cloudiness, the graph remains on the baseline.

In a first series of tests were carried out according to the general Working procedure tested the coated silver-coated silicon dioxide nanoparticles.

A quadruple determination was carried out for each sample. The growth curves are shown in Fig. 2. Fig. 2a shows the growth curve when using coated with polyethyleneimine SiO ₂ nanoparticles, the (calculated as metal) with 2.5 wt .-% silver ions were loaded. An increase in the number of bacteria could not be measured in any of the experiments, whereas in the control experiment to which no nanoparticles were added, a clear increase in the growth curve was found.

In a further series of experiments, the polyurethane films produced in Example 14 were tested for their germicidal effect. In order to remove residues of DMF, the test films for the bioassay were placed in a high vacuum for several days. The growth curves are shown in Fig. 3. Row 1 shows the results obtained with a pure polyurethane film. Series 2 shows the results for a polyurethane film with silver-containing coated silicon dioxide nanoparticles (0.32% by weight Ag). Row 3 shows the results for a polyurethane film with silver-containing coated silicon dioxide nanoparticles (0.53% by weight Ag). Row 4 shows the results obtained with a polyurethane film into which silver-free coated silicon dioxide nanoparticles were incorporated. The figure clearly shows that the polyurethane films with silver-containing coated silicon dioxide nanoparticles have good antimicrobial properties. The tests show that the silver-containing coated silicon dioxide nanoparticles also have sufficient effectiveness against organisms in a polyurethane matrix.

In a further experiment, the antimicrobial activity of the polyurethane strand obtained in Example 16 was checked. In order to remove adhering silver nitrate, the strand was first stirred in distilled water for 8 h, then rinsed several times with water and again treated twice with water for 2 h each. The growth curves obtained with the bioassay are shown in FIG. 4. Row 1 shows the results obtained with the polyurethane strand subsequently coated with silver ions. Row 2 shows the results for a strand that was coated with metallic silver. While a significant slowdown in bacterial growth was observed in the strand coated with silver ions, the test carried out with a conventional silver-containing polyurethane strand showed a significantly smaller delay in bacterial growth. When interpreting the measurement results, particular attention must be paid to the very low silver ion concentration of 0.22% by weight for the polyurethane strand (row 1) subsequently coated with silver ions.

In a further series of experiments, a strand of polyurethane was used, which comprised a larger amount of silver ions. For this purpose, the polyurethane strand was treated as described in Example 16 with a silver ion solution which contained 45.76 mg Ag ⁺ in 50 ml. The results of the bioassay are shown in Fig. 4b. Row 1 shows the polyurethane strand subsequently coated with silver ions, while row 2 shows a comparable strand based on metallic silver. Row 1 clearly shows a bactericidal effect, while row 2 shows only a slight bacteriostatic effect. This result clearly shows that an excellent effectiveness can be achieved with a higher subsequent silver coating.

Claims (37)

1. nanoparticles comprising a carrier and a coating surrounding the carrier, which contains functional groups that act as proton donors or as Electron donors act, whereby at least part of the functional Groups of metal ions are reversibly bound. 2. Nanoparticles according to claim 1, wherein the functional group is selected from a group which is formed from -COOH, -COO-, -CON-, -CONH-, -CONH ₂ , -SH, -SOH, -SO ₂ H, -SO ₃ H, -S-, -SO-, -SO ₂ -, -NH ₂ , -NOH, -NO ₂ H, -NH-, -NO-, -OH, - O-, -SiOH, -Si (OH) ₂ , -Si (OH) ₃ , -SiO-, -Si (O-) ₂ , -Si (O-) ₃ , -PH-, -PH ₂ -, -PO-, -POH-, - POH ₂ , -PO ₂ -, -PO ₂ H-, -PO ₂ H ₂ , -PO ₃ -, -PO ₃ H-, -PO ₃ H ₂ , -PO ₄ -, -PO ₄ H, -PO ₄ H ₂ . 3. Nanoparticle according to claim 1 or 2, wherein the coating is formed by a polymer having a molecular weight of 100 to 10 ⁷ g / mol, preferably 500 to 10 ⁷ g / mol. 4. Nanoparticles according to one of claims 1 to 3, wherein the polymer Is polyalkylene polyamine. 5. Nanoparticles according to one of claims 1 to 3, wherein the polymer Is polyalkylene polyimine. 6. The nanoparticle according to claim 5, wherein the polyalkylene polyimine has a structure of the formula I,
where R ¹ , R ² , R ³ , R ^{4 are} independently:
-H, an alkyl group having 1 to 10 carbon atoms, an aryl group having 5 to 20 carbon atoms or an aralkyl group having 6 to 20 carbon atoms;
A, B independently of one another:
- (CR ⁵ R ⁶ ) -, -C (O) -O-, -C (O) -, -C (O) -N (R ⁵ ) -, -S-, -S (O) -, - S (O) ₂ -, -N (R ⁵ ) -, -O-, -Si (R ⁷ R ⁸ ) -O-, -P (R ⁵ ) -, -P (O) -, -P (OH ) -, -P (O) ₂ -, -P (O) (OH) -, -P (O) (OH) -O-, -OP (O) ₂ -O-,
where A and B can be arranged in any order;
C: -H, -CH ₃ , -COOH, -CONH ₂ , -SH, -SOH, -SO ₂ H, -SO ₃ H, -NH ₂ , -NHOH, -OH, -SiH ₂ OH, -SiH ( OH) ₂ , -Si (OH) ₃ , -PH ₂ , -P (O) H ₂ , -PH (O) OH, -P (O) (OH) ₂ , -OP (O) (OH) ₂ ;
R ⁵ , R ⁶ : independently of one another H, an alkyl group having 1 to 10 carbon atoms;
R ⁷ , R ⁸ : R ⁵ , R ⁶ , OR ⁵ , OR ⁶ ;
m: an integer between 0 and 10;
n: an integer between 0 and 10;
o: an integer between 0 and 1000;
x: an integer between 0 and 10 ⁷ ;
y: an integer between 0 and 10 ⁷ ;
where x + y ≧ 1;
E: a common end group;
R ⁹ , R ¹⁰ : -H, - (A _m B _n ) _o -C. 7. The nanoparticle according to claim 6, wherein the polyalkylene polyimine further comprises structural units of the formula II,
in which R ¹ and R ^{2 have} the meaning given in claim 6 and z is an integer between 0 and 10 ⁷ . 8. Nanoparticle according to claim 6 or 7, wherein the polyalkylene polyimine with a Crosslinker is networked. 9. The nanoparticle according to claim 8, wherein the crosslinker is selected from the group consisting of which is formed from (poly) alkylene polyhalides, (Poly) alkylene glycol bisglycidyl ethers, alkylene carbonates, urea, monoethylenically unsaturated carboxylic acids, at least dibasic saturated carboxylic acids or polycarboxylic acids and their esters, amides and Anhydrides, reaction products of polyether diamines, alkylene diamines, Polyalkylene polyamines, (poly) alkylene glycols, and their mixtures with monoethylenically unsaturated carboxylic acids, esters, amides and anhydrides, wherein the reaction products at least two ethylenically unsaturated Double bonds, carboxamide, carboxyl or ester groups as functional Contain group containing at least two aziridino groups Reaction products of dicarboxylic acid esters with ethyleneimine. 10. Nanoparticle according to one of the preceding claims, wherein the carrier an inorganic material is formed. 11. The nanoparticle according to claim 10, wherein the inorganic material is selected from a group which is formed from Ag, Au, Ni, Pd, Pt, Cr, Cu, Co, Rh, Ru, Ti, Sn, Al and their oxides.   12. The nanoparticle according to claim 10 or 11, wherein the inorganic material is SiO ₂ . 13. The nanoparticle according to claim 12, wherein the SiO _{2 has} been generated in situ. 14. Nanoparticle according to one of the preceding claims, wherein the bound Metal ion is an antimicrobial metal ion. 15. Nanoparticle according to one of the preceding claims, wherein the metal ion is selected from a group which is formed from Ag (I),. , , (Please add), is particularly preferably an Ag (I) ion. 16. Nanoparticle according to one of the preceding claims, wherein the nanoparticle a diameter of 10 to 500 nm along its longest dimension, preferably has 20 to 100 nm. 17. Nanoparticle according to one of the preceding claims, wherein the nanoparticle based on the weight a proportion of metal ions calculated as metal of 0.02 to 5%, preferably 0.1 to 3%. 18. Compound comprising a polymer matrix in which nanoparticles according to one of claims 1 to 17 are embedded. 19. Compound according to claim 18, wherein the polymer matrix of a thermoplastic or a thermosetting plastic is formed. 20. Compound according to claim 18 or 19, wherein the thermoplastic material is selected from a group consisting of polyethylene, polypropylene, Polystyrene, polyurethane, polyester, polyamide and silicones 21. Compound according to claim 18 or 19, wherein the thermosetting plastic is selected from a group consisting of urea-formaldehyde resins, Melamine-formaldehyde resins, urea-glyoxal resins. 22. A method for producing nanoparticles according to one of claims 1 to 17, wherein a carrier is coated with a coating which is functional Contains groups that act as proton donors or electron donors  Obtaining a coated carrier and loading the coated carrier with metal ions becomes. 23. The method of claim 22, wherein the carrier is suspended in a solvent is, the coating is dissolved in the solvent and the carrier with the Coating is coated. 24. The method according to any one of claims 22 or 23, wherein the carrier in situ in Presence of the dissolved coating is generated. 25. The method according to any one of claims 22 to 24, wherein the metal ions during of coating the support with the coating. 26. The method according to any one of claims 22 to 25, wherein the solvent is selected from a group consisting of water, alcohols and their Mixtures. 27. The method of claim 22, wherein the coated carrier is in a first Solvent is suspended, the metal ions in a second solvent be solved, which is essentially immiscible with the first solvent and for loading the metal ions from the second solvent into the first Solvents are transferred. 28. A method for producing a compound according to any one of claims 18 to 21, wherein nanoparticles according to one of claims 1 to 17 in a plastic be introduced. 29. The method of claim 28, wherein the nanoparticles mechanically in the plastic be incorporated. 30. The method of claim 28, wherein the nanoparticles during the manufacture of the Plastic are reacted into the plastic. 31. The method according to claim 28, wherein a suspension of the nanoparticles in one Solvent is generated, the suspension with the plastic, which if necessary with  the solvent may be diluted, combined to obtain a mixture from which the solvent is removed. 32. The method of claim 31, wherein the nanoparticles under the action of Ultrasound can be suspended. 33. The method of claim 31 or 32, wherein rapidly a first portion of the solvent is removed from the mixture to an extent that the viscosity of the Mixing is increased so that the nanoparticles essentially no longer sink and then the remaining solvent is removed. 34. The method according to any one of claims 31 to 33, wherein during the Evaporation of the solvent a temperature of at most 80 ° C, preferably not exceeding 50 ° C. 35. A method for producing a compound according to any one of claims 18 to 21, wherein a coated carrier, which is obtained by a carrier with a coating is coated, which contains functional groups that act as proton donors or act as electron donors, is introduced into a polymer matrix, which Polymer matrix with the coated support, if necessary, into a shape is formed, and the coated carrier is loaded with metal ions. 36. Workpiece consisting of a compound according to one of claims 18 to 21. 37. Use of nanoparticles according to one of claims 1 to 17 as antimicrobial or bacteriostatic agent.