EP3869965A1

EP3869965A1 - Zinc molybdate having a triclinic crystal structure, as an antimicrobial agent

Info

Publication number: EP3869965A1
Application number: EP19790230.7A
Authority: EP
Inventors: J. Peter Guggenbichler
Original assignee: Amistec & Co KG GmbH
Current assignee: Amistec & Co KG GmbH
Priority date: 2018-10-26
Filing date: 2019-10-25
Publication date: 2021-09-01
Also published as: CN113316390A; SG11202106767TA; EP3643177A1; WO2020084155A1; DE202019005334U1; CA3158369A1; BR112021013631A2; WO2020084155A9; JP2022509569A; KR20210110795A; US20220007649A1

Abstract

The invention relates to the use of a triclinic form of zinc molybdate (Zn Mo O₄) as an antimicrobial agent, to composite materials comprising said zinc molybdate and to processes for preparing same.

Description

Zinc molybdate with triclinic crystal structure as an antimicrobial agent

description

The invention relates to the use of a triclinic form of zinc molybdate (ZnMo0 ₄ ) as an antimicrobial active ingredient, composite materials which comprise such zinc molybdate and processes for their production.

In order to prevent the accumulation of microorganisms, the surfaces of objects are treated with antimicrobial agents or endowed with antimicrobial properties. Disinfectants and biocides are used to combat the microorganisms. A major disadvantage of using organic biocides, however, is the development of resistance and cross-resistance among the microorganisms. Therefore, alternatives are increasingly being sought in order to effectively combat microorganisms and to colonize

Prevent surfaces with microorganisms. One possibility is to use metals and metal compounds. Because of their good antimicrobial properties, silver and copper in particular are often used. In a first variant, the elemental metal is provided in a form with the largest possible surface area in order to achieve high activity. Nanoparticles, foamed metal or nanoparticles fixed on a carrier are particularly suitable here. A second variant provides for the provision of soluble metal salts, which are incorporated, for example, in zeolites or directly in a composite material. However, it is disadvantageous that the noble metals or noble metal ions mentioned are comparatively expensive and, moreover, are almost completely inactivated by sulfur-containing compounds or high electrolyte concentrations. The use of molybdate and tungstate as antimicrobial agents has also recently been discussed. These compounds are comparatively inexpensive and also non-toxic since they are practically insoluble in water. However, the antimicrobial effectiveness of the molybdates and tungstates examined so far is often not sufficient.

The object of the present invention is therefore to provide an anti-microbial active ingredient with improved activity and a cost-effective possibility for the effective protection of materials and surfaces against the settlement of microorganisms.

Zinc molybdate, the antimicrobial effect of which has already been described in the field, is usually in a tetragonal crystal structure. It is insoluble in water and therefore practically non-toxic. However, it was surprisingly found in the present invention that zinc molybdate, in addition to the known tetragonal crystal structure, can also be stable in a triclinic crystal structure and in this form shows a significantly higher antimicrobial activity than in other crystal forms. The effect is significantly improved compared to that of tetragonal zinc molybdate with the same grain size.

Triclinic zinc molybdate can be obtained by ultrasonically assisted reaction of a solution of one or more water-soluble molybdates with a solution of one or more water-soluble zinc (II) salts. In the presence of ultrasound, the water-insoluble zinc molybdate formed in the reaction of the educt salts precipitates in the form of triclinic crystals. Depending on the duration of the reaction and the sonication, the grain size of the triclinic crystals can vary.

A particularly good antimicrobial activity has been found according to the invention for zinc molybdate in the form of particles with a triclinic crystal structure and one average grain size in the range from 0.10 miti to 5.0 miti, preferably between 0.25 miti and 5.0 miti.

A first aspect of the invention therefore relates to the use of zinc molybdate as an antimicrobial active ingredient, ZnMo0 ₄ in the form of particles with a triclinic crystal structure and an average grain size between 0.1 miti and 5.0 miti, preferably 0.25 miti and 5.0 miti is present. According to a further embodiment, the use of triclinic ZnMo0 ₄ with an average grain size in the sub-micron range, ie from 0.1 miti to less than 1.0 miti, is preferred.

Triklines zinc molybdate is not toxic to humans and animals and therefore has excellent biocompatibility. It can be produced comparatively inexpensively and shows a strong antimicrobial effect even in small quantities. In addition, zinc molybdate is not inactivated by sulfur-containing compounds or by a high electrolyte concentration, but retains its effectiveness.

Zinc molybdate with a triclinic crystal structure and the grain size given above shows a high antimicrobial activity against a broad spectrum of microorganisms, including algae, fungi and viruses, as well as gram-positive and gram-negative microorganisms regardless of their antibiotic resistance. Examples of microorganisms against which triclinic zinc molybdate according to the invention is active include Lactobacillus acidophilus, Pseudomonas, for example P. aeruginosa, Salmonella, for example S aureus, E. coli, Candida Spp, C. albicans, C. glabrata and C. tropicalis , Legionella, listeria; Fours such as influenza, Ebstein Barr viruses, rotavians and noroviruses; as well as Aspergillus niger, fumigatus and flavus. The antimicrobial effect is significantly increased with the same grain size compared to zinc molybdate with a different crystal structure. In a preferred embodiment of the invention, the zinc molybdate according to the invention is particularly effective against algae growth. The grain size of ZnMo0 _{4 is} preferably in the range from 0.10-2.5 mm, more preferably in the range from 0.15-2.5 m, and more preferably in the range from 0.2 mm to less than 1, 0 miti. Particles smaller than 0.10 miti and in particular nanoparticles are not provided according to the invention. It has been found that with a triclinic crystal structure of zinc molybdate with an average grain size in the micrometer range, excellent antimicrobial activity is achieved, so that the risks associated with nanoparticles can be avoided. Zinc molybdate with a triclinic crystal structure is particularly effective in the submicron range.

Triclinic zinc molybdate itself is water-insoluble. When in contact with water or air humidity, zinc molybdate lowers the pH. The zinc molybdate itself does not go into solution and is not broken down or washed out of a material.

For antimicrobial use, triclinic zinc molybdate can be used alone or in combination with other active substances and / or auxiliary substances. In a particularly preferred embodiment, triclinic zinc molybdate is combined with molybdenum oxide Mo0 ₃ , since this can further improve the antimicrobial effectiveness. M0O3 can exist in any crystal structure, for example orthorhombic or monoclinic. M0O3 with an orthorhomic crystal structure has proven to be particularly advantageous according to the invention. Triklines ZnMo0 ₄ and M0O3 can be in the form of a mixture of crystals or as mixed crystals. The use of a mixture or mixed crystal of triclinic ZnMo0 ₄ and orthorhombic M0O3 is particularly preferred.

Further advantages result when triclinic zinc molybdate in combination with at least one hydrophilizing or hygroscopic agent is used. Particularly preferred hydrophilizing and hygroscopic agents are described below.

According to the invention, triclinic zinc molybdate can be incorporated into a material which is to be provided with antimicrobial properties, or at least deposited on its surface. This results in an antimicrobial composite.

Another object of the invention is accordingly an antimicrobial composite material comprising ZnMo0 ₄ in the form of particles with a triclinic crystal structure and an average grain size between 0.1 pm and 5.0 miti, more preferably between 0.20 pm and 5.0 miti, stronger preferably between 0.25 pm and 5.0 pm, more preferably in the range from 0.50 pm and 2.5 pm and again more preferably in the range from 0.70 pm to 1.5 pm. According to one embodiment, the use of triclinic ZnMo0 ₄ in the composite material with an average grain size in the submicron range, ie from 0.1 pm to less than 1.0 pm, is preferred.

In the context of the present invention, a composite material is understood to mean a material which consists of two or more materials bonded to one another, at least one of the materials being the triclinic zinc molybdate as defined above. The further material can in principle be made of any material and, for example, can itself be a composite material.

The presence of triclinic zinc molybdate gives an inventive composite material an antimicrobial effect. The adherence of pathogenic germs is greatly reduced. The proliferation of microorganisms and the formation of biofilms are inhibited. This is particularly important, for example, in hospitals, nursing homes, etc., since microorganisms in biofilms from antibiotics, organic biocides, disinfectants and the like do not or at least do not are permanently removable. Since a lowering of the pH value is only required in the area of the surface boundary layer of the composite material, or a component or product made from it, correspondingly small amounts of zinc molybdate in the area of the surface are sufficient to achieve the desired antimicrobial effectiveness.

In a preferred embodiment, the adherence of algae and / or biofilms to surfaces is reduced. Accordingly, the use of the zinc molybdate of the invention to prevent fouling, i.e. the undesired settlement of organisms on technical surfaces, e.g. Hulls, a preferred embodiment of the invention.

Triclinic zinc molybdate is essentially not water-soluble, so it does not wash out of the composite, but stays there and its antimicrobial effectiveness is maintained over the entire life of the composite. In this connection it was surprisingly found that triclinic zinc molybdate is retained even better in the material than zinc molybdate with a different crystal structure.

The at least one further material of the composite material can in principle be selected from any material classes. For example, it can be an inorganic, metallic, ceramic or organic material or any combination thereof. Fundamentally, further materials are, for example, plastics, paints, lacquers, silicones, rubber, rubber, melamine, acrylates, methyl acrylates, waxes, epoxy resins, glass, metal, ceramics and others. In a preferred embodiment, the composite material according to the invention comprises at least one organic polymer, or a compound and / or a silicone, as a further material. The material in or on which for the purpose of antimicrobial equipment the triclinic zinc molybdate is introduced can form a solid and / or liquid matrix. It can be provided that triclinic zinc molybdate is added in such a way that it makes up between 0.1% and 10% (percentages by weight or volume) of the total weight or total volume.

The composite material can in principle be designed as a layer composite, fiber composite, particle composite or penetration composite.

In principle, the composite material according to the invention can be solid or liquid under standard conditions. For example, the composite material can be in the form of a solution, suspension and / or dispersion, for example as a lacquer or liquid coating agent. Preference is given to using the zinc molybdate according to the invention as a lacquer or liquid coating agent. Varnishes or coating compositions according to the invention can be applied to any suitable surface such as plastics, metals, wood, stone and other building materials. In such a case, the composite material is hardened after hardening.

Triclinic zinc molybdate can be arranged on the surface of the composite and / or distributed in the composite. An arrangement of triclinic zinc molybdate in the region of the surface of the composite material is preferred according to the invention, since an antimicrobial effect is desired here. For example, zinc molybdate can be applied as a layer or part of a layer to a substrate or carrier material. Basically, only one or more areas of the surface or the entire surface of the composite material can be given antimicrobial properties by triclinic zinc molybdate. As an alternative or in addition, triclinic zinc molybdate can also be arranged within the composite material or distributed in the composite material. This ensures that the antimicrobial effect is permanently retained even if the composite material wears out on the surface. Depending on the intended use, the composite material in the context of the present invention can in principle be present as a semifinished product, ie as a semifinished material, which only reaches its final form of use after further processing steps. Alternatively, the composite material can already be designed as a finished component, which can be used for its intended purpose without further processing steps. A composite material according to the invention can contain triclinic zinc molybdate alone or in combination with other active substances and / or auxiliary substances. In a particularly preferred embodiment, triclinic zinc molybdate is combined with molybdenum oxide Mo0 ₃ , since this can further improve the antimicrobial effectiveness. M0O3 can exist in any crystal structure, for example orthorhombic or monoclinic. M0O3 with an orthorhomic crystal structure has proven to be particularly advantageous according to the invention. Triklines ZnMo0 ₄ and M0O3 can be in the form of a mixture of crystals or as mixed crystals. The use of a mixture or mixed crystal of triclinic ZnMo0 ₄ and orthorhombic M0O3 is particularly preferred.

In a preferred embodiment, a composite material according to the invention has, in addition to triclinic ZnMo0 ₄ and possibly M0O3, no additional antimicrobial compounds, such as silver or silver compounds, in particular nanosilver or soluble silver compounds such as silver nitrate or the like. Copper, organic biocides, zeolites and the like are preferably also not contained in a composite material according to the invention. In this way, better environmental compatibility and a significant reduction in costs are achieved. The mass content of triclinic zinc molybdate based on the total mass of the composite material is advantageously between 0.1 and 80% by weight, in particular between 1.5 and 30% by weight and preferably between 1.8 and 5.0% by weight. This mass ratio ensures a particularly high antimicrobial activity with the least possible use of zinc molybdate.

The use of particles with the average grain sizes mentioned offers the particular advantage that, on the one hand, a particularly high antimicrobial activity can be achieved and, on the other hand, the composite material according to the invention is free of nanoparticles. In addition, the introduction of ZnMo0 ₄ with grain size according to the invention does not lead to clouding of the correspondingly doped composite materials. Clear lacquers remain clear even after the ZnMo0 ₄ according to the invention has been introduced.

Further advantages result if triclinic zinc molybdate is used in combination with at least one hydrophilizing or hygroscopic agent which is arranged at least in the area of the surface of the composite material. In this way, the antimicrobial effectiveness in particularly dry environments, that is to say, for example in the case of very low atmospheric humidity and correspondingly small amounts of water which are important for the formation of an acidic surface boundary layer, is substantially increased. Examples of suitable hydrophilizing and / or hygroscopic agents are in particular SiO ₂ , in particular in the form of silica gel or as pyrogenic silicon dioxide. These form a kind of moisture buffer and thus guarantee a minimum moisture level in the product. In addition, it was found that the association of triclinic zinc molybdate with SiO _{2 has the} effect that triclinic zinc molybdate is retained particularly well in the composite material and washing out can be completely prevented. Si0 ₂ is preferably with a Particle size distribution in the range between 0.25 miti and 25 miti mean particle diameter used.

Further examples of other hydrophilizing and / or hygroscopic agents which can be used according to the invention are organic acids, such as abietic acid, arachidonic acid, arachic acid, behenic acid, capric acid, caproic acid, cerotic acid, erucic acid, fusaric acid, fumaric acid, bile acids, icosenoic acid, isophthalic acid, lactonic acid, lauric acid, lauric acid, lauric acid Linolenic 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, undecanoic acid, stearic acid, stearic acid, stearic acid, stearic acid . Furthermore, malonic acid, maleic acid and maleic anhydride, lactic acid, acetic acid, citric acid, salicylic acid and ascorbic acid, and their salts have proven to be advantageous. Acid anhydrides, ampholytic substances, buffer systems, polymer acids, ion exchange resins, and also acid sulfonates and acid halides can also be used.

The mass content of hydrophilizing and / or hygroscopic agent based on 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% be. A mass content in the range between 1 and 5%, preferably in the range of 2-4%, is particularly advantageous. Furthermore, the mass content or the mass ratio of the hydrophilizing and / or hygroscopic agent can be adjusted such that it corresponds to the selected mass content of triclinic zinc molybdate. In a particularly preferred embodiment, triclinic zinc molybdate is at least partially coated and / or agglomerated with the hydrophilizing and / or hygroscopic agent, in particular SiO ₂ . This ensures a spatial proximity of the two classes of compounds in a simple manner, so that zinc molybdate is supplied directly with the moisture required for lowering the pH value even under particularly dry conditions.

In a further aspect of the present invention, the use of an antimicrobially active composite material as defined above is provided for producing an antimicrobially active product.

Another aspect of the invention relates to a method for producing an antimicrobially active composite material as defined above. For this purpose zinc molybdate is preferably in the form of particles with an average grain size between 0.10 and 5.0 miti, more preferably in the range from 0.15 pm to less than 1.0 miti, more preferably 0.20 miti to less than 1.0 miti and even more preferably 0.25 pm to less than 1 pm and provided with at least one further material.

Triclinic zinc molybdate can be prepared by ultrasonically assisted reaction of one or more water-soluble molybdates with one or more water-soluble zinc (II) salts. For this purpose, aqueous solutions of molybdate and zinc salt are provided separately and brought into contact under the influence of ultrasound. The presence of ultrasound causes zinc molybdate to crystallize out in a triclinic crystal structure. The particle size of the zinc molybdate can be adjusted by the duration and intensity of the ultrasound. In a preferred embodiment of the invention, triclinic zinc molybdate is prepared by contacting an aqueous solution of one or more alkali or alkaline earth molybdates with an aqueous solution of one or more zinc (II) salts. As water-soluble zinc molybdate, for example Sodium molybdate dihydrate can be used. For example, a zinc halide such as zinc chloride can be used as the zinc (II) salt. The two salt solutions are preferably reacted at room temperature in the presence of ultrasound at a frequency of more than 15 kHz, in particular 20-30 kHz. For the best possible effectiveness, zinc molybdate must be present in a crystal lattice that is as error-free as possible. This is ensured by ultrasound treatment. A mixture of the reactants such as water-soluble molybdates with one or more water-soluble zinc salts without the addition of energy does not lead to the formation of an optimal crystal structure, which is expressed by a lack or reduced effectiveness compared to the optimal crystal structure according to the invention.

The production of triclinic ZnMn0 ₄ by means of ultrasound also enables, in particular, the defined provision of particles in the submicron range, ie greater than 0.1 pm and less than 1 pm in the sense of the invention.

In the manufacture of a composite material, the triclinic zinc molybdate is advantageously combined with at least one hydrophilizing and / or hygroscopic agent as defined above, the hydrophilizing and / or hygroscopic agent being arranged at least in the region of the surface of the composite material. It has proven to be particularly advantageous to coat and / or agglomerate zinc molybdate at least partially with the hydrophilizing and / or hygroscopic agent, in particular SiO ₂ .

The lack of water solubility of zinc molybdate according to the invention was demonstrated in wipe tests. After wiping 10,000 times with a water-alcohol mixture of melamine resin samples comprising zinc molybdate according to the invention, neither zinc molybdate nor zinc nor molybdenum could be detected in the wiping textile. However, the antimicrobial effect of the corresponding melamine resin samples was unchanged. The present invention is further illustrated by the following figures and examples. characters

1 shows the antimicrobial activity of different crystal forms of zinc molybdate: 1) monoclinic ZnMo0 ₄ with orthorhombic MO0 ₃ ; 2) triclinic ZnMo0 ₄ with orthorhombic Mo0 ₃ ; 3) monoclinic ZnMo0 ₄ with amorphous Mo0 ₃ . Triclinic zinc molybdate is clearly superior to other crystal forms and shows that the examined sample is completely sterile after 6 hours.

The effectiveness studies were carried out with 3 ATCC reference germs (S. aureus ATCC 25923, E. coli ATCC 25022 and P.aeruginosa ATCC

15442). All germs listed were sensitive. No resistant germ was found; Lactobacillus acidophilus (acid resistant) was also eradicated.

Fig. 2 shows the antimicrobial effectiveness of two different Si0 ₂ coatings on hospital tables (coating I & coating II) with 0.2 pm grain size of zinc molybdate against Staphylococcus aureus. The coatings comprising zinc molybdate according to the invention show a marked reduction after 1 or 3 hours and complete sterility after 6 hours.

Claims

Expectations

1. Use of zinc molybdate (ZnMo0 ₄ ) as an antimicrobial agent, ZnMn0 _{4 being} in the form of particles with a triclinic crystal structure and an average grain size between 0.1 miti and 5.0 miti.

2. Use according to claim 1, wherein the average grain size of ZnMo0 _{4 is} in the range from 0.15 miti to less than 1.0 miti, preferably in the range from 0.20 miti to less than 1.0 miti.

3. Use according to claim 1 or 2, wherein ZnMo0 ₄ in combination with MO0 ₃ , preferably orthorhombic Mo0 ₃ is used.

4. Antimicrobial composite, comprising ZnMo0 ₄ in

Form of particles with a triclinic crystal structure and an average grain size between 0.1 pm and 5.0 miti and at least one other material.

5. The antimicrobial composite according to claim 4, further comprising Mo0 ₃ with a preferably orthorhombic crystal structure which is present in a mixture or as a mixed crystal with the triclinic ZnMo0 ₄ .

6. The antimicrobially active composite material according to claim 4 or 5, further comprising at least one flydrophilizing and / or flygroscopic agent which is arranged at least in the region of the surface of the composite material.

7. The composite material according to claim 6,

characterized in that

the ZnMo0 _{4 is} at least partially coated and / or agglomerated with the flydrophilizing and / or flygroscopic agent.

8. The composite material according to claim 6 or 7, wherein the hydrophilizing and / or hygroscopic agent comprises Si0 ₂ , in particular silica gel or pyrogenic silicon dioxide.

9. Composite material according to one of claims 4 to 8,

characterized in that

the mass content of ZnMo0 ₄ based on the total mass of the composite material is 0.1% to 80%, in particular 1.5% to 30% and preferably 1.8% to 5.0%.

10. Composite material according to one of claims 3-9

characterized in that

the further material comprises at least one organic polymer and / or silicone.

11. Composite material according to one of claims 3-10

characterized in that

it is designed as a layer composite, fiber composite particle combination or penetration composite.

12. Use of an antimicrobial composite according to one of claims 3-11 for the production of an antimicrobial product.

13. A method for producing an antimicrobially active composite material according to one of claims 3-11,

characterized in that

ZnMo0 ₄ in the form of particles with an average grain size between 0.20 pm and 5.0 miti, preferably 0.25 pm and 5.0 pm with at least one other material.

14. The method according to claim 13,

characterized in that

the ZnMo0 _{4 is} produced by ultrasound-assisted reaction of one or more water-soluble molybdates with one or more zinc (II) salts in aqueous solution.

15. The method according to claim 16,

characterized in that

an aqueous solution of sodium molybdate dihydrate at room temperature with an aqueous solution of zinc chloride

Presence of ultrasound with a frequency of more than 15 kHz, in particular 20-30 kHz, is implemented.

16. The method according to any one of claims 13-15

characterized in that

at least one hydrophilizing and / or hygroscopic agent is arranged at least in the area of the surface of the composite material.

17. The method according to claim 16,

characterized in that

ZnMo0 _{4 is} at least partially coated with the hydrophilizing and / or hygroscopic agent and / or agglomerated.