Improved tungsten-containing antibacterial composites

Abstract

The present invention relates to the use of tungsten blue as an antimicrobial agent, to a composite material comprising tungsten blue, and to a method for preparing the same.

Description

[Technical field]

[0001] explanation The present invention relates to the use of tungsten blue as an antimicrobial agent, to a composite material comprising tungsten blue, and to a method for preparing the same. [Background technology]

[0002] To prevent the accumulation of microorganisms, the surfaces of the articles are treated with antimicrobial agents or equipped with antimicrobial properties. Among others, bactericides and biocides are used to combat microorganisms. However, the main disadvantage of the use of organic biocides is the development of resistance and cross-resistance among microorganisms. Therefore, alternatives are increasingly being considered to combat microorganisms efficiently and prevent the population of surfaces with microorganisms. One possibility is the use of metals and metal compounds. Due to their good antimicrobial effect, in particular silver and copper are often used. In a first variant, elemental metals are provided in a form with the largest possible surface area in order to achieve a high level of activity. In particular nanoparticles, metal foams or nanoparticles fixed on a support should be considered in this regard. A second variant provides for the provision of soluble metal salts, which are incorporated, for example, in zeolites or directly in the composite material. However, a disadvantage is that the abovementioned noble metals or noble metal ions, respectively, are relatively expensive and, moreover, are almost completely inactivated by sulfur-containing compounds or high electrolyte concentrations.

[0003] Recently, the use of compounds containing molybdenum and tungsten, especially molybdates and molybdenum oxides, as well as tungstates and tungsten oxides, as antimicrobial agents has also been discussed. These compounds are relatively inexpensive and also non-toxic since they are practically insoluble in water. Tungsten(VI) oxide (WO3) is a crystalline powder that has a brilliant yellow color at room temperature and orange when heated. The crystal lattice of orthorhombic WO3 consists of WO6 octahedra connected by common angles in three spatial directions. Tungsten trioxide is completely insoluble in water and acid, but can react with water to form tungstic acid. The biocidal effect of tungsten trioxide is based on the associated decrease in the pH value in the surrounding medium. However, the antimicrobial efficacy of WO3 and other molybdenum and tungsten compounds tested so far is often insufficient.

[0004] WO 2015 / 091993 describes an antibacterial active composite and a method for preparing the corresponding antibacterial active material. The printed document does not disclose the use of tungsten blue as an antibacterial active composite, where the tungsten blue is oxygen-deficient WO3 minus 1-10 mol % oxygen or WO3 minus 5 mol % oxygen. Furthermore, highly effective preparations of oxygen-deficient WO3 with particles of preferred particle size are not described. No reference to the oxygen content of WO3 is given in the printed document WO 2015 / 091993. A mixture of oxygen-saturated tungsten yellow and oxygen-deficient tungsten blue appears blue and is commonly and therefore often erroneously generally referred to as tungsten blue. Summary of the Invention [Means for solving the problem]

[0005] It is therefore an object of the present invention to provide antimicrobial agents with improved activity and to provide a cost-effective possibility to effectively protect materials and surfaces against microbial populations.

[0006] In addition to tungsten trioxide, other oxides of tungsten are also known. Yellow tungsten(VI) oxide will eventually change to brown tungsten(IV) oxide when exposed to reducing agents. Reduction of the newly precipitated tungsten(VI) oxide hydrate will result in WO3+ xH → WO 3-x (OH) x A deep blue solution of hydrated mixed oxides of hexavalent to pentavalent tungsten is obtained. These blue tungsten(VI)-tungsten(V) mixed oxides are collectively called "tungsten blue".

[0007] In the present invention, it has been surprisingly found that tungsten blue exhibits significantly higher antibacterial activity than tungsten trioxide. At the same particle size, the efficacy of tungsten blue is significantly better than that of tungsten trioxide.

[0008] Thus, a first aspect of the present invention relates to the use of tungsten blue as an antimicrobial agent.

[0009] According to the present invention, "tungsten blue" refers to oxygen-deficient tungsten trioxide in which tungsten exists in an oxidation state between VI and V. In contrast, "tungsten yellow" is oxygen-saturated tungsten trioxide. In particular, tungsten blue can be described as WO3 minus about 1-10 mol % oxygen, more preferably WO3 minus about 4-6 mol % oxygen, preferably WO3 minus about 5 mol % oxygen, most preferably minus 5 mol % oxygen. Thus, "oxygen-deficient WO3" according to the present invention preferably describes WO3 minus about 5 mol % oxygen. In particular, tungsten blue according to the present invention, i.e. tungsten blue that is preferably 5% oxygen-deficient, has been found to have excellent antibacterial activity and to be active against a wide variety of bacteria. In this connection, it should be noted that tungsten oxide containing small amounts of tungsten blue already has a bluish color. The mixture of tungsten yellow with tungsten blue appears blue, and is therefore generally often (mistakenly) called tungsten blue. Preferably, tungsten yellow or oxygen-saturated WO3 is not present in the corresponding tungsten blue preparation. However, for the purposes of the present invention, tungsten blue is actually understood to mean only oxygen-deficient WO3, in particular WO3 minus about 5 mol % oxygen. Preferably, oxygen-saturated WO3 (tungsten yellow) is not present.

[0010] According to the present invention, preferably, a tungsten blue preparation is used that is substantially free of oxygen-saturated WO3 (tungsten yellow) or free of oxygen-saturated WO3 (tungsten yellow), respectively. Preferably, the antimicrobial composite according to the present invention thus has no oxygen-saturated WO3 (tungsten yellow) content. Since oxygen-saturated WO3 is not antimicrobially active, the proportion of tungsten contained in the composite can be kept lower without loss of antimicrobial activity by completely omitting oxygen-saturated WO3.

[0011] Tungsten blue is non-toxic to humans and animals and therefore exhibits excellent biocompatibility. It can be produced relatively cheaply and exhibits strong antibacterial activity even in small amounts.

[0012] Tungsten blue has high antibacterial activity against a wide range of microorganisms, including fungi and viruses, as well as gram-positive and gram-negative microorganisms, regardless of their antibiotic resistance. Examples of microorganisms against which tungsten blue is effective according to the present invention include, but are not limited to, Lactobacillus acidophilus, Pseudomonas, such as P. aeruginosa, Salmonella, such as S. aureus, E. coli, Candida Spp, C. albicans, C. glabrata and C. tropicalis, Legionella, Listeria monocytogenes; viruses, such as influenza, Epstein-Barr virus, rotavirus and norovirus; and Aspergillus niger, fumigatus and flavus. The antibacterial activity is significantly increased at the same particle size compared to tungsten (VI) oxide (yellow).

[0013] In a particularly preferred embodiment, the oxygen-deficient tungsten blue according to the invention is used as an antibacterial agent against S. aureus, E. coli and / or P. aeruginosa.

[0014] According to the present invention, particularly good antimicrobial efficacy has been found for tungsten blue in the form of particles having an average particle size between 0.1 and 0.9 μm. Preferably, the average particle size of tungsten blue is in the range of 0.2-0.7 μm, more preferably in the range of 0.25-0.5 μm. Particles smaller than 0.1 μm, and in particular nanoparticles, are not provided by the present invention. It has been found that excellent antimicrobial efficacy can be achieved using tungsten blue in the particle size ranges mentioned above, so that the risks associated with nanoparticles can be avoided. A particularly preferred embodiment relates to the use of oxygen-deficient WO3, i.e. WO3 minus about 5 mol % oxygen (tungsten blue), as an antimicrobial agent, where the tungsten blue is in the form of particles having an average particle size between 0.20-0.5 μm, and more preferably between 0.25-0.5 μm, and the tungsten blue preparation preferably has no particles having a particle size less than 0.1 μm. The prior art does not provide any hint to the skilled artisan as to the superior combination of corresponding characteristics. This applies in particular to the "tungsten blue compositions" cited in the prior art.

[0015] Advantageously, according to the invention, tungsten blue is used which is essentially free of particles having a size smaller than 0.1 μm. Even more preferably, it is substantially free of particles having a size larger than 0.9 μm. The narrow particle size distribution ensures a particularly high antibacterial efficacy while avoiding the risks associated with nanoparticles.

[0016] Tungsten blue itself is insoluble in water. When in contact with water or atmospheric moisture, tungsten blue causes a drop in pH. Tungsten blue itself does not dissolve and decompose or wash out of materials.

[0017] For antimicrobial uses, tungsten blue may be used alone or in combination with other active ingredients and / or excipients. Preferably, WO3 is absent.

[0018] Further benefits arise when tungsten blue is used in combination with at least one hydrophilizing or moisture absorbing agent. Particularly preferred hydrophilizing and moisture absorbing agents are described below.

[0019] According to the invention, tungsten blue can be incorporated into or at least deposited on the surface of the material to be endowed with antimicrobial properties, thus resulting in an antimicrobially active composite material.

[0020] Therefore, a further object of the present invention is an antimicrobially active composite material comprising tungsten blue and at least one further material, wherein the average particle size of the tungsten blue is preferably between 0.1 μm and 0.9 μm, more preferably between 0.2 and 0.7 μm and particularly preferably between 0.25 μm and 0.5 μm, as described above. Particles smaller than 0.1 μm and in particular nanoparticles are not provided by the present invention. The composite material according to the present invention preferably does not contain oxygen-saturated WO3 (tungsten yellow).

[0021] For the purposes of the present invention, a composite material is understood to be a material consisting of two or more materials bonded together, where at least one of the materials is tungsten blue as defined above. The further material can in principle be formed from any material and can also, for example, itself constitute a composite material.

[0022] The presence of tungsten blue gives the composite material according to the invention an antibacterial effect. The adhesion of pathogenic bacteria is reduced to a considerable extent. The growth of microorganisms and the formation of biofilms are inhibited. For example, this is particularly important in hospitals, nursing homes, etc., since the microorganisms in biofilms cannot be eliminated, or at least not permanently, by antibiotics, organic biocides, disinfectants, etc. Since a reduction in pH is only required in the area of ​​the surface boundary layer of the composite material, or of the part or product made therefrom, a correspondingly small amount of tungsten blue in the area of ​​the surface is sufficient to achieve the desired antibacterial efficacy.

[0023] Tungsten blue is not essentially water soluble and therefore will not be washed out of the composite material but will remain there and maintain its antimicrobial efficacy throughout the life of the composite material.

[0024] At least one further material of the composite material can in principle be selected from any type of material. For example, it can be an inorganic, metallic, ceramic or organic material or any combination thereof. In principle, the further material can be, for example, plastic, paint, lacquer, silicone, rubber, rubber, melamine, acrylate, methyl acrylate, wax, epoxy resin, glass, metal, ceramic and others. In a preferred embodiment, the composite material according to the invention comprises at least one organic polymer, or compound and / or silicone as further material. Examples of organic polymers include polyethylene (PE) and polypropylene (PP).

[0025] For antimicrobial devices, the material into or onto which tungsten blue is introduced may form a solid and / or liquid matrix. It may be provided that tungsten blue is added to constitute between 0.1% and 10% (weight percent or volume percent) of the total weight or volume. Preferably, the amount of tungsten blue is 1-3% by weight.

[0026] In principle, the composite material may be formed as a layered composite, a fiber composite, a particulate composite or an interpenetrating composite.

[0027] In principle, the composite material according to the invention can be in solid or liquid form under standard conditions, for example it can be in the form of a solution, suspension and / or dispersion, for example as a lacquer or liquid coating, respectively.

[0028] Tungsten blue can be arranged on the surface of the composite material and / or distributed in the composite material. Preferably, according to the present invention, tungsten blue is arranged at least in the area of ​​the surface of the composite material (where the antibacterial effect is desired). For example, tungsten blue can be applied to the substrate or carrier material as a layer or a component of a layer. In this case, the substrate or carrier material is not substantially subject to structural or material constraints. In principle, only one or more areas or the entire surface of the composite material can be provided with antibacterial properties by tungsten blue. Alternatively or additionally, tungsten blue can also be arranged or distributed in the composite material, respectively. This ensures that the antibacterial effect is permanently maintained even when the composite material is worn away on its surface.

[0029] Depending on the intended use, the composite material in the context of the present invention can essentially exist as a semi-finished product, i.e. as a semi-finished material, which will only obtain its final use form after further processing steps. Alternatively, the composite material can already be designed as a finished product that can be used for its desired intended purpose without further processing steps.

[0030] In the composite material according to the invention, tungsten blue may be present alone or in combination with other active ingredients and / or adjuvants.

[0031] In a preferred embodiment, the composite material according to the invention does not have any additional antibacterial active compounds, such as silver or silver compounds, in particular soluble silver compounds such as nanosilver or silver nitrate, in addition to tungsten blue. Copper, organic biocides, zeolites, etc. are also preferably not present in the composite material according to the invention. In this way, improved environmental compatibility and a significant reduction in costs are achieved. Preferably, tungsten yellow is also not present.

[0032] The mass content of tungsten blue relative to the total mass of the composite material is advantageously between 0.1 and 80 wt.%, in particular between 1.0 and 30 wt.%, and preferably between 1.5 and 5.0 wt.%. This mass ratio ensures a particularly high antibacterial efficacy with the lowest possible raw material input of tungsten blue.

[0033] In principle, any auxiliary agent common in the art can be considered as an auxiliary agent in the composite material according to the present invention. It is understood that possible auxiliary agents can vary depending on the specific materials of the composite material. Preferably, conventional dispersants, antistatic agents, wetting agents, emulsifiers, etc. are used.

[0034] The use of particles having the aforementioned average particle sizes offers the particular advantage that, on the one hand, a particularly high antibacterial efficacy can be realized and, on the other hand, the composite material according to the invention is free of nanoparticles.

[0035] Further advantages arise when the tungsten blue, which is placed at least in the surface region of the composite material, is used in combination with at least one hydrophilizing or moisture absorbing agent. In this way, the antibacterial efficacy is substantially increased in particularly dry environments, i.e., for example, environments with very low humidity and correspondingly low amounts of available water, which are important for the formation of an acidic surface boundary layer. Examples of suitable hydrophilizing and / or moisture absorbing agents include SiO2, especially in the form of silica gel or as fumed silica. These form a kind of humidity buffer and therefore ensure a minimum moisture content in the product. It has also been found that the association of tungsten blue with SiO2 causes tungsten blue to be particularly well retained in the composite material and can be completely prevented from being washed off. SiO2 with a particle size distribution in the range of average particle sizes between 0.25 μm and 25 μm is preferably used.

[0036] Further examples of other hydrophilizing and / or hygroscopic agents which may be used according to the invention are organic acids such as abietic acid, arachidonic acid, arachidic acid, behenic acid, capric acid, caproic acid, cerotic acid, erucic acid, fusaric acid, fumaric acid, bile acid, icosenoic acid, isophthalic acid, lactonic acid, lauric acid, lignoceric acid, linoleic acid, levopimaric acid, linoleic acid, margaric acid, melissic acid, montanic acid, myristic acid, neoabietic acid, nervonic acid, nonadecanoic acid, oleic acid, palmitic acid, palmitoleic acid, pelargonic acid (nonanoic acid), pimaric acid, palustric acid, palmitic acid, ricinoleic acid, stearic acid, sorbic acid, tannic acid, tridecanoic acid, undecanoic acid and vulpic acid. In addition, malonic acid, maleic acid and maleic anhydride, lactic acid, acetic acid, citric acid, salicylic acid and ascorbic acid, and their salts have proven advantageous. Acid anhydrides, amphoterics, buffer systems, polymeric acids, ion exchange resins, and acid sulfonates and acid halides may also be used.

[0037] The mass content of the hydrophilizing agent and / or the moisture absorbing agent relative to the total weight of the composite material is advantageously in the range of 0.1% and 15%. For example, the mass content can be 0.5%, 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13% or 14%. Particularly advantageous are mass contents in the range between 1 and 5%, preferably in the range of 2-4%. Furthermore, the mass contents or mass ratios of the hydrophilizing agent and / or the moisture absorbing agent can be adjusted to correspond to the selected mass content of tungsten blue.

[0038] In a particularly preferred embodiment, tungsten blue is at least partially coated with a hydrophilizing agent and / or moisture absorbing agent, in particular SiO2, and / or aggregated with the hydrophilizing agent and / or moisture absorbing agent, in particular SiO2. This ensures in a simple manner the spatial proximity of the two compounds, so that tungsten blue is directly supplied with the moisture required to lower the pH value, even under particularly dry conditions.

[0039] In another aspect of the present invention there is provided the use of an antimicrobially active composite material as defined above for the manufacture of an antimicrobially active product.

[0040] Another aspect of the present invention relates to a method for the preparation of an antimicrobially active composite material as defined above. For this purpose, tungsten blue is combined with at least one further material.

[0041] Advantageously, in the preparation of the composite material, tungsten blue is combined with at least one hydrophilizing agent and / or moisture absorbing agent as defined above, where the hydrophilizing agent and / or moisture absorbing agent is arranged at least in the area of ​​the surface of the composite material. It has proven to be particularly advantageous to at least partially coat the tungsten blue with the hydrophilizing agent and / or moisture absorbing agent, in particular SiO2, and / or to aggregate with the hydrophilizing agent and / or moisture absorbing agent, in particular SiO2.

[0042] The invention is further illustrated by the following figures and examples. [Brief description of the drawings]

[0043] [Figure 1] Figure 1 shows the antibacterial efficacy of tungsten blue (1% in WO3 5% oxygen deficient, TPU) against the bacteria S. aureus and E. coli. After only 9 h, the tested samples are completely sterile. [Diagram 2] Figure 2 shows a comparison of the effectiveness of molybdenum (VI) oxide, tungsten (VI) oxide and tungsten blue with various mixtures against S. aureus. Sample No. 1: MoO3, No. 2, 3, 6: WO3 (tungsten yellow), No. 4, 7: tungsten blue (WO3 5% oxygen deficient), No. 5, 8, 9: mixture WO3 (yellow) / tungsten blue, No. 10: control. Tungsten blue is clearly superior to WO3 (yellow) and shows almost complete sterility of the tested samples after 6 h. Tungsten blue and tungsten yellow mixtures are also much less effective than pure tungsten blue. [Diagram 3] Figure 3 shows a comparison of the antibacterial efficacy of tungsten yellow and tungsten blue at different concentrations: G11: 1% WO3 (yellow) G12: 2% WO3 (yellow) G13: 1% tungsten blue G14: 2% tungsten blue Already at lower concentrations, tungsten blue is significantly more effective. [Figure 4] Figure 4 shows the efficacy of tungsten blue against S. aureus depending on particle size and in comparison with tungsten yellow. Tungsten oxide is used at a concentration of 2% each. For tungsten blue (5% oxygen deficient), particle sizes of 0.25 μm and 5 μm are compared. The particle size of tungsten yellow is 0.5 μm. [Diagram 5] Figure 5 shows a test of the effectiveness of tungsten blue and tungsten yellow in combination with various additives. The bacteria were S. aureus (left), E. coli (right) and P. aeruginosa (bottom), respectively. The following materials were tested:5A:62:PE+2%WO3(blue)+1%Disperplast 115063:PE+2%WO3(yellow)+1%Disperplast 101864:PE+2%WO3(blue)+1%Atmer 129MB65:PE+2%MoO3+1%Palsgaard DMG009366:PE+1%Lubrophos LM-400E5B:15:PP+2%WO3(yellow / blue)+1%Crodafos MCA-SO16:PP+2%WO3(blue)+1%Lubrophos LM-400E17:PP+2%WO3(blue)+1%Pluronic PE 810018:PP+2%WO3(yellow)+1%Surfynol 440 19: PP + 2% WO3 (yellow) + 1% sodium dodecyl sulfate Additionally, the average bacterial load at the beginning of the test (T=0 h) and after 12 h is shown. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0044] The efficacy of tungsten blue is significantly better against all bacteria than all other tested agents. It is also shown that the mixture of tungsten yellow and tungsten blue is significantly less effective than tungsten blue alone.

Claims

1. 1. Use of tungsten blue as an antimicrobial agent, wherein the tungsten blue is oxygen-deficient WO3, and the tungsten blue is present in the form of particles having an average particle size between 0.1 μm and 0.9 μm, and no particles having a particle size less than 0.1 μm are present.

2. The use of tungsten blue according to claim 1, wherein the tungsten blue is oxygen deficient WO 3 -1 to 10 mol % oxygen, and / or the tungsten blue is present in the form of particles having an average particle size in the range of 0.2 to 0.7 μm.

3. The use of tungsten blue according to claim 1, wherein the tungsten blue is oxygen deficient WO 3 -5 mol % oxygen and / or the tungsten blue is present in the form of particles having an average particle size in the range of 0.25 to 0.5 μm.

4. An antimicrobially active composite material comprising tungsten blue according to any one of claims 1 to 3 and at least one further material.

5. 5. The antimicrobially active composite material of claim 4, further comprising at least one hydrophilizing agent and / or moisture absorbing agent disposed at least in a surface region of the composite material.

6. 6. The composite material of claim 5, wherein the tungsten blue is at least partially coated with and / or aggregated with the hydrophilizing agent and / or the moisture absorbing agent.

7. 7. The composite material of claim 5 or 6, wherein the hydrophilizing agent and / or moisture absorbing agent comprises SiO2.

8. The composite material according to any one of claims 4 to 7, wherein the mass content of tungsten blue relative to the total mass of the composite material is 0.1% to 80%.

9. A composite material according to any one of claims 4 to 8, wherein the further material comprises at least one organic polymer and / or silicone.

10. The composite material of any one of claims 4 to 9, formed as a layered composite, a fiber composite, a particulate composite, or an interpenetrating composite.

11. Use of the antimicrobially active composite material according to any one of claims 4 to 10 for the manufacture of an antimicrobially active product.

12. A method for producing an antimicrobially active composite material according to any one of claims 4 to 10, wherein tungsten blue is combined with at least one further material.

13. 13. The method according to claim 12, wherein at least one hydrophilizing agent and / or moisture absorbing agent is disposed at least in the surface region of the composite material.

14. 14. The method of claim 13, wherein the tungsten blue is at least partially coated with a hydrophilizing agent and / or a moisture absorbing agent and / or is aggregated with the hydrophilizing agent and / or the moisture absorbing agent.

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