WO2015107476A1

WO2015107476A1 - Method for production of antimicrobial coating in low temperatures, and metallic material, natural or artificial, coated with metal oxide nanolayers of disinfecting action and neutral to mucous membranes

Info

Publication number: WO2015107476A1
Application number: PCT/IB2015/050305
Authority: WO
Inventors: Sylwia GIERAŁTOWSKA; Łukasz WACHNICKI; Bartłomiej WITKOWSKI; Marek GODLEWSKi
Original assignee: Instytut Fizyki Pan
Priority date: 2014-01-15
Filing date: 2015-01-15
Publication date: 2015-07-23
Also published as: PL406853A1; EP3094762A1

Abstract

This invention relates to a low-temperature method of production of antimicrobial coatings on the surface of metallic materials, natural and artificial materials, and in particular on the surface of fibers. Materials covered with such coatings may be used in broadly understood medicine as personal protection means (protective masks) or as medical and/or surgical instruments exposed to bacteria and viruses (particularly of Escherichia coli or Staphylococcus aureus), and metallic material, natural or artificial, coated with metal oxide nanolayers of disinfecting action and neutral to mucous membranes.

Description

Method for production of antimicrobial coating in low temperatures, and metallic material, natural or artificial, coated with metal oxide nanolayers of disinfecting action and neutral to mucous membranes

This invention relates to a low-temperature method of production of antimicrobial coatings on the surface of metallic materials, natural and artificial materials, and in particular on the surface of fibers. Materials covered with such coatings may be used in broadly understood medicine as personal protection means (protective masks) or as medical and/or surgical instruments exposed to bacteria and viruses (particularly of Escherichia coli or Staphylococcus aureus type ) .

Publication: Y. Li et al. Antimicrobial effect of surgical masks coated withnanoparticles Journal of Hospital Infection (2006) 62, 58-63, describes substrates covered with layers consisting of a combination of nanoparticles of silver nitrate and titanium dioxide which show antimicrobial effect against e- coli strains (Escherichia coli, Staphylococcus aureus). Those coatings were obtained according to the method described in Chinese patent No. 03142467 (Li Y, Hu JY, Song QW. Nano multifunctional broadspectrum microbial protective materials and surface depositing methods, June 10, 2003). The obtained coatings are durable, unfortunately silver nitrate has a harmful influence upon human health since it irritates skin. From publication: Zhang et al. Plasma surface modification of poly vinyl chloride for improvement of antibacterial properties Biomaterials 27 (2006) 44-51, method of covering a synthetic polymer (polyvinyl chloride) with organic chemical compounds of triclosan and bronopol type is known, followed by the modification of their surface with implantation of ions immersed in plasma in order to improve their bactericidal properties. The polyvinyl chloride used in this work was purchased from Beijing Huaer corporation while the coating with organic compounds was made by Tian Jing Well-Real Chemical Technology corporation. A polymer covered with bactericidal layer is commonly used in medicine in the form of drains, probes, or catheters. However, the organic layers deposited on such polymer are not resistant to weather conditions and they also often cause skin or eyes irritation. It is known that metallic silver is the most popular element with disinfecting and antimicrobial properties, and there are many works devoted to this issue in the literature. This includes publication: Ivan Sondi et al. Silver nanoparticles as antimicrobial agent: a case study on E. coli as a model for Gram-negative bacteria Journal of Colloid and Interface Science 275 (2004) 177-182, where application of silver nanoparticles to hinder development of Escherichia coli bacteria was described. In order to examine the bacteria growth rate and the influence of presence of silver nanoparticles upon the said growth, the bacteria were grown in 100 cm³ of liquid medium for microbial culturing bakterii, with the addition of 10, 50, and 100 \iq of those particles for 1 cm³ of the medium. The bacteria growth rate and concentration were determined by measuring the optical density for the wavelength of 600 nm every 30 minutes. A similar method of hindering bacterial growth is used with silver nanoparticles in bactericidal applications for Staphylococcus aureus (Stephan Thierry Dubas et al. Tunning of the antimicrobial activity of surgical sutures coated with silver nanoparticles Colloids and Surfaces A: Physicochem. Eng. Aspects 380 (2011) 25-28). Currently, many surgical instruments are coated with silver in order to minimize the risk of bacterial infections, unfortunately, however, it is a costly solution due to the cost of this metal. From publication by G.K. Hyde et al. Atomic layer deposition and biocompatihility of titanium nitride nano- coatings on cellulose fiber substrates Biomed. Mater. 4 (2009) 025001 (lOpp), a method is known for protecting medical equipment against bacterial growth by coating the former with organic, biologically neutral materials applied with ALD method. The ALD method was also applied to coat cellulose fibers (used in antiseptic masks) with titanium nitride at 100 °C. Unfortunately, as one of reagents for growth process ammonia was used, which is a toxic compound, irritating skin and mucous membranes. From America patent application US20060240662A1 , a method of depositing nO with ALD method is known, which is not universal, i.e. it may not be applied for materials sensitive to temperatures above 100 °C like flammable materials, e.g. cellulose masks. The purpose of this invention is to develop a low-temperature, cost effective and simple method of producing coating hindering bacterial growth, free from side effects, including no irritation to mucous membranes, on the surface of tools, instruments, and devices and on personal protection means. Coatings that can be deposited in temperatures not exceeding 200°C, which allows covering thermally sensitive materials (getting damaged in higher temperatures) with them. The second purpose of this invention is to provide a material covered with nanolayers of metal oxides, which does not contain compounds potentially harmful to mucous membranes, wherein the content of precursor derivatives and compounds used for preparation of the material prior to coating should not exceed a few percent by weight in one layer, preferably not more than 2%. Unexpectedly, the problems mentioned above have been solved by the present invention.

The first object of this invention is a low-temperature process of producing antibacterial, neutral for mucous membranes, coatings on the surface of tools, instruments, equipment, and nonwoven personal protection means, with thin layer deposition method, characterized in that a coating is deposited upon the surface of the said materials in the temperature from 20 °C to 200°C, preferably with ALD technique, consisting of at least one oxide material layer ≥ 1 ran thick, preferably ZnO or Ti0₂, or Zr0₂, or Hf0₂, or Al₂0₃, whereby, for metallic surfaces, the depositing is preceded with cleaning with organic solvents and deionized water. Organic solvents are for example: ketones, alcohols, acids, and aldehydes. For depositing the coating with ALD technique, the depositing is carried out in at least 5 cycles with nontoxic organic or inorganic precursor as metal precursor, and water as oxygen precursor, preferably deionized, or ozone, the precursor doses ranging from 0.015-2s. Equally preferably, the depositing can be effected with other chemical gaseous phase deposition techniques, like Chemical Vapor Deposition (CVD), Molecular Beam Epitaxy (MBE), Metalorganic Vapor Phase Epitaxy (MOVPE), Pulsed Laser Deposition (PLD), or sputtering. For some applications, e.g. on natural and artificial materials fabrics, particularly on fibrous surfaces, i.e. surgical masks or gauze, a binding layer of zinc oxide (ZnO) of the thickness not exceeding 0.5 nm is deposited on the clean nonwoven surface prior to depositing oxide material coating, and the deposition process with ALD method is carried out in a temperature below 140 °C, more preferably 100 °C not causing thermal damage to the fabric .

The second object of this invention is a metallic material, natural or artificial, coated with metal oxide nanolayers of disinfecting action, characterized in that the layer consists of metal oxides and neutral to mucous membranes precursor derivatives used for obtaining the said layer in the thin layer deposition process, preferably with ALD method. Equally preferably, the material according to the present invention is characterized in that the said metal oxides are nO, Ti0₂, Zr0₂, Hf0₂, or Α1₂03· More preferably, the precursor derivatives according to the invention are OH ions, carboxyl groups and derivatives of elements included in the composition of the precursors. Equally preferably, the oxygen precursor in metal oxides is water. In the following preferable embodiment of the invention, the percentage (% by weight) of neutral to mucous membranes precursor derivatives does not exceed 2%.

The proposed method is economic and simple, yet it enables obtaining a layer which hinders the growth of bacteria commonly present in nature, the most often on skin, membranes, and in the digestive tract of people and animals, as well as in the air, dust, and soil (Escherichia coli, Staphylococcus aureus). Additionally, the coating protects the coated surface against effects of external factors such as bodily fluids. What's more, the coating is neutral to mucous membranes and its production does not require application of special precautions unlike in case of using hazardous precursors or solvents thereof such as ammonia or ozone.

The invention shall be explained in more detail using embodiments of antibacterial coating on surgical mask nonwoven and on the surface of a surgical instrument like the steel scalpel blade acting like the substrate.

Example 1 :

In the method of the example the coating consists of a thin buffer layer 5 nm thick in the form of zinc oxide (ZnO) layer, and aluminum oxide (Al₂0₃) layer 100 nm thick. According to the example, the layer is deposited with ALD technique as one of the possible thin layer depositing techniques available for implementation. ALD technique is a variation of chemical vapor deposition, CVD, consisting in alternating feeding reagents, called precursors, to the reaction chamber where the layer of the desired metal is deposited upon the substrate as the result of chemical reaction of exchange or synthesis . After each precursor dose, the reaction chamber is purge with inert gas. A typical metal depositing cycle in ALD process consists of four steps: dosing the first precursor, purging, dosing the second precursor, purging. The layer thickness is determined by the number of cycles. An example nonwoven substrate was covered with a conformal layer of zinc oxide and then with a layer of aluminum oxide as the result of reaction between inorganic precursors (reagents). The ZnO layer was deposited in 100 ALD cycles, then the Al₂0₃ layer in 1600 ALD cycles. The layers were made at the growth temperature of 20 °C. In the depositing process of these layer, diethyl zinc DEZ was used as the zinc precursor, trimethylaluminum, TMA, as the aluminum precursor, and deionized water as the oxygen precursor (in both layers). The growth parameters were set as follows: DEZ precursor pulse: 0.04s; purging after DEZ pulse: 10s; oxygen precursor pulse: 0.015s; purging after H₂0 pulse: 20s for the ZnO layer, and TMA precursor pulse: 0.015s; purging after TMA pulse: 10s; oxygen precursor pulse: 0.015s; purging after H20 pulse: 20s for the AI2O3 layer. For purging between consecutive precursor doses, inert gas, which is nitrogen, N₂ of high purity - 99.9999% was used. The resulting layer uniformly covers and protects the nonwoven substrate against bacteria.

Example 2 : on a nonwoven substrate, a thin buffer layer of 5 nm zinc oxide (ZnO) layer and of 100 nm aluminum oxide (A1₂0₃) layer was deposited in the ALD reactor chamber. The ZnO layer was performed in 30 ALD cycles at the growth temperature of 80 °C, The ZnO layer was performed in 30 ALD cycles at the growth temperature of 80°C, In the depositing process of these layer, diethylzinc DEZ was used as the zinc precursor, trimethylaluminum, TMA, as the aluminum precursor, and deionized water as the oxygen precursor (in both layers). The growth—parameters were set as in example 1. For purging Between^" consecutive precursor doses, inert gas, which is nitrogen, N₂ of high purity - 99.9999% was used.

Example 3: A steel substrate in the form of a surgical blade was cleaned with, in sequence, organic solvents like acetone and isopropanol, and then with deionized water. An aluminum oxide (AI₂O₃) layer of 100 nm was deposited on the cleaned substrate in the reaction chamber of an ALD reactor. The layer was performed in 1100 ALD cycles at the growth temperature of 200 °C. In the process of depositing those layers, trimethylaluminum, TMA, was used as the aluminum precursor, and deionized water as the oxygen precursor. The growth parameters were set as in examples 1 and 2. For purging between consecutive precursor doses, inert gas, which is nitrogen, N₂ of high purity - 99.9999% was used.

The method of obtaining oxide layers having antimicrobial properties, as described above, is simple and relatively short since it does not require complex multi-stage substrate preparation processes like etching or high temperature annealing. The growth may occur in relatively low temperatures ranging from 20-200°C, which, due to the character of the used substrates often made of natural or artificial fabrics, is particularly important. What is more, the remaining precursor derivatives are neutral to mucous membranes.

Claims

1. Low-temperature process of producing antibacterial, neutral for mucous membranes, coatings on the surface of tools, instruments, equipment, and nonwoven personal protection means, with thin layer deposition method, characterized in that a coating is deposited upon the surface of the said materials in the temperature from 20°C to 200°C, preferably with ALD technique, consisting of at least one oxide material layer ≥ 1 nm thick, preferably ZnO or Ti0₂, or Zr0₂, or Hf0₂, or A1₂0₃, whereby, for metallic surfaces, the depositing is preceded with cleaning with organic solvents and deionized water.

2. Low-temperature method of claim 1, characterized in that the oxide coating is deposited in at least 5 ALD cycles, with nontoxic organic or inorganic precursor as metal precursor, and water as oxygen precursor, preferably deionized, or ozone, the precursor doses ranging from 0.015-2s.

3. Low-temperature method according to claim 1 characterized in that prior to depositing the oxide layer upon the clean nonwoven surface, a binding oxide layer of more than 0.5 nm is deposited, preferably by means of ALD technique, and the ALD process is run at a temperature belowe 140 °C, more preferably 100 °C, not causing thermal damage to the fabric.

4. Metallic material, natural or artificial, coated with metal oxide nanolayers of disinfecting effect, characterized in that the layer consists of metal oxides and neutral to mucous membranes derivatives of precursors used for obtaining the said layer in the thin layer deposition process, preferably with ALD method.

5. Material according to claim 4 characterized in that the said metal oxides are ZnO, Ti0₂, Zr0₂, Hf0₂, or Al₂0₃.

6. Material according to claim 4 characterized in that the precursor derivatives are OH ions, carboxyl groups and derivatives of elements included in the composition of the precursors.

7. Material according to claim 4 characterized in that the oxygen precursor in metal oxides is water.

8. Material according to claim 4 characterized in that the percentage content (% by weight) of precursor derivatives does not exceed 2% of the layer.