HK1118305B - Method and use of nanoparticles to bind biocides in paints - Google Patents

Description

Method for combining nano-particles and biological pesticide in coating and application

Cross Reference to Related Applications

This application claims priority from U.S. provisional application No. 60/661,083, filed on 11/03/2005, which is incorporated herein by reference.

Background

Technical Field

The present invention relates to a method and use of binding imidazole compounds, such as Medetomidine (Medetomidine), to metal nanoparticles in antifouling coatings to develop an effective antifouling surface and improve the performance of antifouling coatings, allowing for uniform release of distributed fixation of the biocide in the coating matrix and effective prevention of, for example, barnacle colonization. Other pesticide systems can use the same nanoparticle interactions to achieve uniform release from their non-marine antifouling coatings.

Description of the Related Art

The growth of fouling organisms on underwater structures is an expensive and dangerous problem for marine and freshwater installations. The presence of fouling organisms such as barnacles, algae, tubeworms and the like can cause various forms of economic loss: for example, adhesion to the hull reduces fuel efficiency and reduces profitability time due to the need to clean the hull. Similarly, the attachment of these fouling organisms to refrigeration equipment can reduce heat transfer, which ultimately results in reduced refrigeration efficiency of the equipment and increased operating costs. Other marine industries and equipment, such as aquaculture installations and oil/gas sea surface equipment and plants, also have significant problems with marine biofouling.

Mechanical removal of marine surfaces has been described as an alternative to toxins and biocides. In particular, water jet cleaning and mechanical cleaning with brushes are used. However, most of these methods are labor intensive and costly.

The most effective antifouling coatings are "self-polishing copolymer" coatings based on a polymeric binder chemically combined with biocidal organotin, particularly tributyltin, which is gradually hydrolysed by seawater in the coating, as described for example in british patent GB-a-1457590. These organotin copolymer coatings prevent fouling by releasing organotin compounds during hydrolysis of the polymer. The outermost coating is depleted of biocide and is removed from the hull surface due to the movement of the ship through the water. The organotin copolymer coating also contains copper oxide pigments which are effective against fouling by marine organisms, while tributyltin protects clays and aquatic plants.

Coatings containing organotin compounds, particularly tributyltin, have been shown to have negative environmental consequences, damaging marine life, resulting in oyster deformation and conch denaturation. It has been noted that organotin compounds degrade slowly and as a result these compounds accumulate in localized areas of the deposit. Many countries and international organizations have therefore promulgated limitations and bans on these applications and are expected to impose even stronger limitations. The sale and application of TBT antifouling was agreed to stop at the international maritime association antifouling systems conference in month 10 2001. Treaty calls for banning applications from 1/2003 and completely banned on the hull by 1/2008.

Due to the recent start of restrictions on the use of these toxic coatings in many countries, the ship owners have to switch to copper oxide based coatings with lower technology but also lower toxicity. Under normal fouling conditions, the lifetime of copper oxide coatings rarely exceeds 2 years, while the lifetime of self-polishing tributyltin coatings is 5 years.

The copper oxide coating is not satisfactory and it does not meet the requirements of the operators and owners of ships and vessels, nor the requirements of the environmental protection organisation because of its toxicity to the environment. When the use of copper compounds is reduced in concentration for ecological reasons, these coatings require secondary biocides against barnacles and algae to achieve an effect acceptable to boat owners and other types of marine industry owners.

Recent advances in the field of self-polishing coatings include the use of zinc acrylate copolymers using ion exchange as the release mechanism.

Concern over the potential environmental effects of antifouling toxins has prompted the development and use of systems that attempt to control fouling by surface modification, for example, by using polymers containing silicon or fluorine with non-stick or release properties to prevent adhesion, for example, as described in the patents WO-0014166a1, US92105410, JP53113014, US92847401, DE2752773, EP874032a2, and EP885938a 2. These coatings have been shown to be easily embrittled, resulting in cracking and flaking of the surface.

A new alternative technology was introduced as early as the 90 s. Although this technique is also known as a self-polishing technique, the process by which it is obtained no longer passes through hydrolysis of the polymer. But in combination with a different water-sensitive and partially water-soluble binder, such as a resin, alone or in a mixture with acrylates, as described in european patent EP0289481, EP 526441. Experience has shown that such coatings have not been able to provide as high and reliable performance as hydrolyzed organotin coatings.

Recently, new polymers have been developed which are based on the same principle as organotin polymers, i.e. hydrolysis of an insoluble polymer to provide a slightly water-soluble product. Such as the self-polishing polymers described in WO 8402915. Instead of incorporating organotin groups into the polymer chain, the incorporation of organosilicon groups is described herein. Experiments have shown that these coatings have many of the characteristics associated with organotin copolymer technology. However, it has also been found that cracking and peeling of the surface of these coatings can occur over time. This leads to exudation of soluble constituents, with the result that a residual layer is formed which differs from the original coating composition.

One approach to solve this problem is to modify silyl polymers with different comonomers, as described in EP0646630, EP1016681 and EP 1127902. Another approach is to add fibres to enhance and increase the cohesive strength throughout the coating, in particular the residual layer formed, as described in WO 0077102. A third approach is to develop a coating in which a mixture of silicone copolymer and resin is used to reduce residual layer build-up, as described in EP 0802243. Use is made of low molecular weight plasticizers, more particularly chlorinated paraffins, as described in EP 0775733.

Along the swedish west coast as well as along the coast of the north atlantic ocean, barnacles and algae are economic and technical problems. Mature barnacles are a fixed crustacean characterized by a centimeter-sized cone shape and a surrounding layer of calcified discs. The mechanical strength of the animal's adsorbed solid surface is very high and thus it is difficult to mechanically remove barnacles from the solid surface. The animal undergoes different stages of development, namely free-swimming larvae, with the last larval stage being referred to as the cyprid stage. The cyprid screens solid surfaces suitable for attachment with the aid of neurites. An "adhesive" refers to the glans mucus secreted from a particular gland above the protrusion to attach the animal to a solid surface. After attachment, the animal undergoes metamorphosis into an adult and sessile animal. One of the first organisms that fouled when using old copper bleed paint with high copper concentrations was barnacles.

Also, algae are relatively insensitive to copper and the amount of copper leaching required to inhibit fouling of algae is high. Thus, copper-containing marine antifouling paints are "aided" with more specific algicides produced by certain manufacturers. The algicide can inhibit zoospore fouling or inhibit photosynthesis. Both methods result in a reduction in algal fouling.

Future biocide assisted antifouling coatings should have high specificity, i.e. act only on fouling organisms and not on other marine machinery. The coating should also be designed to enable controlled release of the active substance. An effective way to achieve controlled release is to form a bond with a macromolecule. Due to the large size and low variability of the macromolecules, the diffusion of the biocide through the coating film is controlled and thus a release rate is obtained which depends only on the polishing rate of the self-polishing coating. Furthermore, biodegradation of the antifouling agent is another important aspect in order to prevent accumulation in water and sediments, and the resulting effects on the marine environment, rather than just the target biofouling.

Several compounds have shown antifouling activity. Some of these compounds are pharmacological agents known to have pharmacological effects in vertebrates. It has been reported that a pharmacological compound selected from the group consisting of serotonin and dopamine neurotransmitters is capable of hindering or promoting barnacle attachment. Serotonin antagonists such as cyproheptadine and ketanserin; dopamine agonists such as R (-) -propylnoraporphine and (+) -bromocriptine all have inhibitory properties. Another pharmacological agent that has proven to be effective in inhibiting barnacle attachment is the highly selective alpha adrenergic receptor agonist medetomidine or (S, R) -4(5) - [1- (2, 3-dimethylphenyl) ethyl ] -1H-imidazole. The agent can prevent adhesion of larvae at low concentrations, 1nM to 10 nM. Medetomidine belongs to a novel alpha 2-receptor agonist, comprises a 4-substituted imidazole ring, and has high selectivity on 2-adrenergic receptors. Receptors affected by catecholamine neurotransmitters, such as norepinephrine and epinephrine, are referred to as adrenergic receptors (or adrenoceptors) and can be classified into alpha-and beta-subspecies. Alpha 2-adrenoceptors are involved in the mechanism of automatic inhibition of neurotransmitter release and play an important role in the regulation of hypertension (high blood pressure), bradycardia (slow heart rate), even regulation of alertness and analgesia (reduced pain sensitivity). Medetomidine has been studied in human clinical trials and used as an animal anesthetic with (S) -enantiomer, dexmedetomidine as the active ingredient.

Nanoparticles are nano-sized metal and semiconductor particles and have recently been extensively studied in the field of nano-scale materials. Nanoparticles have potential applications in many different fields. These applications include: nanoelectronics, multifunctional catalysts, chemical sensors, and many biological applications such as biosensors, biological detection, bio-transfection using gene gun technology, and drug delivery.

Two important factors result in the properties of nanomaterials being significantly different from other materials: relative surface area increase and quantum effects. These factors may alter or improve the properties of the nanomaterial, such as reactivity, strength, and electrical properties. As the particle size decreases, more atoms are found to be bound to its surface than inside the particle. For example, a particle size of 30nM has 5% of the atoms on its surface, a particle size of 10nM has 20% of the atoms on its surface, and a particle size of 3nM has 50% of the atoms on its surface. Thus, there is a greater surface area per mass unit of nanoparticles than larger particles. When surface growth and catalytic chemistry occur, this means that a material in nano form of a given mass is more active than a material consisting of larger particles of the same mass. (see "nanoscience and nanotechnology: opportunities and uncertainties", 29/07/2004, proceedings of the royal academy of engineers, uk).

Likewise, the use of nanoparticles in coatings for anti-fouling and other applications has been discussed above, but that is to modify the structure of the coating surface, for example to make it more attractiveThin, smoother to reduce fouling of marine structures (cf. environmental application and effects of nanotechnology "published by proceedings of the royal academy of engineers of uk, uk 12.08.2003) or rougher to reduce fouling (cf. pollution reduction of marine structures)http://innovation.im-boot.org/modules.php？ name＝News&file＝article&sid＝129) But not the concept of using nanoparticles to specifically bind biocides as disclosed in the present invention.

It is therefore an object of the present invention to provide a method and product for use in antifouling products such as paints, which utilizes nanoparticles of metals, metal oxides, silica gels, etc. in combination with biocides. Other objects and advantages will be more clearly understood from the following description and appended claims.

Disclosure of Invention

The invention herein relates to a method and use of imidazole-containing compounds such as medetomidine in antifouling coatings to bind to metal nanoparticles to specifically and effectively prevent the attachment of barnacles to underwater structures. Medetomidine was surprisingly found to be strongly adsorbing to nano-metals and nano-silica gels, which has attracted particular attention and has been tried to develop an effective antifouling surface and improve the performance of antifouling coatings, allowing for the uniform release of distributed fixation of the biocide in the coating matrix and effectively preventing colonization of e.g. barnacles. Other biocidal systems can use the same nanoparticle interactions to achieve uniform release from their non-marine antifouling coatings.

Drawings

FIG. 1 shows the chemical structure of the antifouling agent studied: a) chlorothalonil, b) dichlofluanid (N' -dimethyl-N-phenylthioamide), c) SeaNine [ SeaNine^TM(4, 5-dichloro-2-n-octyl-3 (2H) -isothiazolone) was produced by Rohm and Haas Company, Philadelphia, Pennsylvania]，d)Irgarol (2-methylsulfanyl-4-tert-butylamino-6-cyclopropylamino-s-triazine), e) Diuron (3- (3, 4-dichlorophenyl) -1, 1-dimethylurea), produced by DuPont Agricultural products Wilmington, Germany; f) and tolylfluanide (N- (dichlorodifluoromethylthio) -N ', N' -dimethyl-N-p-toluenesulfonamide).

FIGS. 2a) and 2b) show the adsorption rate of the antifouling agents (medetomidine, chlorothalonil, dichlofluanid, SeaNine, Irgarol, Diuron and tolylfluanid) and the surface area of the nanoparticles (m²) The nanoparticles in fig. 2a) are ZnO nanoparticles in o-xylene and the nanoparticles in fig. 2b) are CuO nanoparticles in o-xylene.

FIG. 3 shows the adsorption rate of medetomidine to ZnO (< 53nm), TiO in o-xylene₂(＜40nm)、CuO(33nm)、Al₂O₃(＜43nm)、SiO₂Surface area (m) of (10nm), MgO (12nm) nanoparticles and CuO (5 μm)²) A graph of the relationship (c).

FIG. 4 is a graph of medetomidine adsorption rate versus surface area (m) of ZnO and CuO nanoparticles in o-xylene, acetonitrile and butanol²) A graph of the relationship (c).

Figure 5 is a graph of medetomidine release (nanograms) versus time (weeks) for ZnO and CuO nanoparticles-medetomidine modified coatings and medetomidine modified marine coatings.

Fig. 6 is a graph of the release amount (nanograms) of medetomidine and SeaNine versus time (weeks) for ZnO and CuO nanoparticles-medetomidine modified marine coatings or ZnO and CuO nanoparticles-SeaNine, medetomidine modified marine coatings.

Detailed description and preferred embodiments of the invention

Recently unpublished studies have shown that: nanoparticles such as copper (II) oxide and zinc (II) oxide (33 and 35nm in diameter, respectively) can be used to maintain controlled release, for example the antifouling agent medetomidine. The use of nanoparticles is due to their large specific surfaceVolume (ratio of particle surface area to volume). The specific surface areas generated by CuO and ZnO particles are respectively 29 and 21m²/g。

Significant differences in the interaction were observed when CuO and ZnO nanoparticles were mixed with medetomidine and other antifouling agents such as chlorothalonil, dichlofluanid, SeaNine, Irgarol, Diuron and tolylfluanid in o-xylene. Most medetomidine adsorbs even at low particle concentrations, especially when ZnO nanoparticles are used. This makes it possible to design a coating system comprising a low content of medetomidine and nanoparticles that limits the diffusion of the antifouling agent through the coating film. The adsorptivity of medetomidine has a high advantage over other antifouling agents listed above. The above-listed antifouling agents show a common feature, nitrogen being present in all compounds in the form of secondary or tertiary amines, nitrile groups, or heterocycles. However, studies have shown that the imidazole moiety of medetomidine has an optimal geometry for adsorption to the particle surface.

To investigate the importance of large surface areas, we investigated medetomidine with various metal oxide nanoparticles (ZnO, CuO, Al)₂O₃，MgO，TiO₂) And silica gel (SiO)₂) Interaction of nanoparticles and one micron-sized particle, CuO (5 μm). When using microparticles instead of nanoparticles, the adsorption of medetomidine was negligible. These results show the importance of a large adsorption surface area when medetomidine is adsorbed on the particle surface.

It is another object of the invention to produce an antifouling method that requires low biocide dosages, with ecological and economic advantages. To improve performance and reduce environmental impact, it is very important to properly control the release of the anti-fouling substances in the coating film. Medetomidine molecules combine with nano-sized metal oxides to form a compound that can control the leaching of the coating into water. Due to the large size of the compounds, medetomidine molecules in combination with nanosized metal oxides have very good diffusion stability compared to medetomidine particles alone. Because of their size characteristics, medetomidine-metal oxide particles are stable in SPC paint films and do not leak into water. Thus, the concentration of anti-fouling particles in the coating film remains consistent during the "life" period.

The metal nanoparticles and silica gel nanoparticles provide a large number of binding sites for medetomidine, to which a large number of medetomidine can bind. The medetomidine concentration is therefore uniform throughout the coating film. So that desorption will be at a uniform level and minimum amount of medetomidine is required to achieve antifouling effect. Another effect is that the total surface area of the nanoparticles is sufficient to adsorb all medetomidine without wasting the biocide.

When exposed to water, the medetomidine of the surface layer detaches from the metal oxide and desorbs from the surface. The surface active substances in the antifouling paint are therefore likely to have a greater effect on the attachment of barnacle larvae than the compounds that leak from the paint into the water, since surface activity increases the concentration near the surface.

Nanoparticles provide a large number of binding sites for biocides due to the large surface area relative to size. Therefore, when the metal nanoparticles are used, the amount of the metal oxide to be used can be reduced, thereby reducing the negative effect of the metal oxide on the environment.

Medetomidine according to the invention is relatively harmless compared to the toxic substances currently used for ship coatings. In fact, medetomidine according to the invention is not so harmful as to be approved for use as an oral pharmaceutical formulation. Medetomidine is also biodegradable, so that the substance accumulates less in the organism. Other imidazole containing biocides, for example, the antifungal miconazole is used. Imidazoline-containing compounds such as spiroimidazoline "Catemine 3" (S18616{ (S) -spiro [ (1-oxa-2-amino-3-azetidin-2-ene) -4, 29- (89-chloro-19, 29, 39, 49-tetrahydronaphthalene) ].

Example 1

Study of interaction of various nanoparticles with biocides

Materials and methods

A total concentration of 50mM biocide was added to 50ml o-xylene solvent. Nanoparticles (Sigma-Aldrich Sweden, Inc. of Sweden, Sweden) were then added at relevant concentrations according to the protocol, and the concentration of non-adsorbed medetomidine was checked after each addition by standard HPLC-UV techniques (Orion Pharma, Helsinki, Finland). According to the literature, medetomidine has a UV maximum absorption of 220 nm. Prior to HPLC analysis, UV absorbance maxima were analyzed using a UV-spectrometer (GBC 920 UV/visible spectrophotometer, provided by scientific instruments ltd, victoria, australia) to determine the literature values.

Sample analysis was performed using HPLC-UV system including a Merck-Hitachi L-6200 pump (Merck-Hitachi, Darmstatt, Germany), a Supelco DiscoveryC18 column (25 cm. times.4.6 mm, 5m) equipped with a prefilter (0.5 μm) and a Spectra-Physics 100 UV spectrometer (Spectra-Physics, Irvine CA, USA) operating at 220nm (Sigma-Aldrich Sweden Co., Ltd., Sweden, Stockholm, Sweden). The mobile phase is Milli-Q water: acetonitrile (0.1% trifluoroacetic acid TFAv/v (mobile phase A): 0.1% trifluoroacetic acid TFAv/v (mobile phase B)), a flow gradient of 2 minutes 6% mobile phase B, 15 minutes 60% mobile phase B, 3 minutes 100% mobile phase B, equilibration for 3 minutes, 2 minutes before returning to the starting value, the flow rate is 10 ml/min. Peak separation was monitored using an ultraviolet detector (220 nm). 100 microliters were manually injected and data was collected and integrated using Millenium software (version 3.20, 1999) (Waters corporation, MilfordMA, usa).

Results

A significant difference in their interaction was observed when CuO and ZnO nanoparticles were mixed with medetomidine and other antifouling agents such as chlorothalonil, dichlofluanid, SeaNine, Irgarol, Diuron and tolylfluanid in o-xylene [ see figures 1, 2a) and 2b) ]. Most medetomidine is adsorbed even at low particle concentrations, especially when ZnO nanoparticles are used. This makes it possible to design a coating system comprising a low content of medetomidine and nanoparticles that limits the diffusion of the antifouling agent through the coating film. The adsorptivity of medetomidine has a high advantage over the other antifouling agents listed above. The antifouling agents listed above show a common feature; nitrogen is present in all compounds in the form of secondary or tertiary amines, nitrile groups or heterocycles. However, studies have shown that the imidazole moiety of medetomidine has an optimal geometry for adsorption to the particle surface.

It should be noted that although medetomidine showed the best adsorption, in this study some other compounds, in particular SeaNine, Diuron, Irgarol, also showed adsorption.

Example 2

Study of interaction of nanoparticles of various sizes with biocides

Materials and methods

Different nanoparticles (ZnO, CuO, Al) purchased from Sigma (Sigma-Aldrich Sweden, Inc. of Stockholm, Sweden) were used₂O₃、MgO、TiO₂、SiO₂) And used without further purification. To a large beaker containing 50ml of medetomidine (Orion Pharma, Helsinki, Finland) was added 50ml of o-xylene. The nanoparticles were then added and after each addition the amount of free medetomidine was measured using HPLC-UV detection techniques (as described in example 1 above).

Results

To investigate the importance of large surface areas, we investigated medetomidine with various metal oxide nanoparticles (ZnO, CuO, Al)₂O₃、MgO、TiO₂) Nano silica gel (SiO)₂) And one micron-sized particle of CuO (5 μm)Interaction (see figures 3 and 4). When microparticles are used instead of nanoparticles, the adsorption of medetomidine is extremely minimal. These results indicate the importance of a large adsorption surface area when medetomidine is adsorbed on the particle surface.

Example 3

Release Rate Studies of biocides on nanoparticles

Materials and methods

The coatings selected for these studies were self-polishing coatings, xylene as solvent, and self-polishing Lefant marine coatings from Lotrec ltd (Lindingo, Sweden), to which was added 50ml of a solution containing 10g of nanoparticles (CuO and ZnO) (Sigma-Aldrich Sweden ltd., stockholm, Sweden), surface adsorbed medetomidine (Orion Pharma, helsiny, finland) or SeaNine (rlimes & Haas, philadelphia, pa, usa), and stirred well for 5 minutes to allow mixing. 3 samples were prepared and applied using a paint applicator to ensure a uniform coating thickness, 200 microns in this experiment. The applied surface is 10 × 10cm, and is placed in artificial seawater for 8 weeks.

Results

Medetomidine-nanoparticle interactions (medetomidine-CuO and medetomidine-ZnO) were used for release rate studies (see figure 5). After 8 weeks, the release of medetomidine in the medetomidine-nanoparticle modified coating decreased by 20% compared to the medetomidine coating as additive. Figure 6 shows the results of SeaNine-nanoparticle interactions, demonstrating a similar reduced release as medetomidine-nanoparticles.

Example 4

Preparation of antifouling paint by combining nano-particles and biological pesticide

An example of a typical coating selected for medetomidine modified coatings was studied, which included xylene as the primary solvent (self-polishing Lefant marine coating from Lindingo, Lotrec, ltd., sweden), in order to prepare a coating containing both nanoparticles and biocides, the two components were first mixed in a solvent that provides strong adsorption of the biocide, such as xylene. Typically, 10 grams of nanoparticles are mixed with up to 10% excess of non-adsorbed medetomidine in 50ml of xylene (using a simple magnetic stirrer), after complete adsorption (usually a few minutes of mixing) the solution is slowly added to the coating and stirred thoroughly (using a propeller type shearer at 0.5-2 Hz) until the coating becomes homogeneous, typically for 5-10 minutes, depending on the stirring rate.

Nanoparticles were purchased from Sigma (Sigma-Aldrich Sweden ltd, stockholm, Sweden) and used without further purification, medetomidine was purchased from Orion Pharma, helsinki, finland.

While the invention has been described in conjunction with specific embodiments, it is intended that various changes, modifications, and embodiments be practiced, and accordingly, all such changes, modifications, and embodiments are to be considered as within the spirit and scope of the present invention.

Claims (20)

1. A method for preventing fouling of a substrate by marine organisms, the method comprising applying to the substrate a protective coating comprising a coating of a material selected from the group consisting of metal oxide nanoparticles and SiO₂Nanoparticle-bound imidazole-containing compounds.

2. The method of preventing marine biofouling of a substrate of claim 1, wherein the imidazole-containing compound is medetomidine.

3. The method of preventing marine biofouling of a substrate according to claim 1, wherein the metal oxide nanoparticles are selected from the group consisting of CuO, ZnO, TiO₂、Al₂O₃And MgO, said SiO₂The nanoparticles are silica gel nanoparticles.

4. The method of preventing fouling of a substrate by marine organisms according to claim 3, wherein the metal oxide nanoparticles are CuO.

5. The method of preventing marine biofouling of a substrate according to claim 3, wherein the metal oxide nanoparticles are ZnO.

6. The method of preventing biofouling of a substrate by a marine organism of claim 1, wherein the protective coating further comprises ortho-xylene.

7. The method of preventing biofouling of a substrate by a marine organism of claim 1, wherein the protective coating further comprises a marine coating.

8. The method for preventing marine biofouling of a substrate of claim 1, wherein the imidazole-containing compound is medetomidine, and a metal oxide nanoparticle or SiO₂Nanoparticles of a metal oxide selected from the group consisting of CuO, ZnO, TiO₂、Al₂O₃And MgO, said SiO₂The nanoparticles are silica gel nanoparticles.

9. The method of preventing fouling of a substrate by marine organisms according to claim 8, wherein the metal oxide nanoparticles are CuO.

10. The method of preventing marine biofouling of a substrate according to claim 1, wherein the metal oxide nanoparticles are ZnO.

11. A product for preventing fouling of a substrate by marine organisms, the product comprising a protective coating comprising a coating of a material selected from the group consisting of metal oxide nanoparticles and SiO₂Nanoparticle-bound imidazole-containing compounds.

12. The product for preventing marine biofouling of a substrate of claim 11, wherein the imidazole-containing compound is medetomidine.

13. The product for preventing marine biofouling of a substrate according to claim 11, wherein the metal oxide nanoparticles are selected from the group consisting of CuO, ZnO, TiO₂、Al₂O₃And MgO, said SiO₂The nanoparticles are silica gel nanoparticles.

14. The product for preventing fouling of a substrate by marine organisms according to claim 13, wherein the metal oxide nanoparticles are CuO.

15. The product for preventing marine biofouling of a substrate according to claim 13, wherein the metal oxide nanoparticles are ZnO.

16. The product for preventing biofouling of a substrate by a marine organism of claim 11, wherein the protective coating further comprises ortho-xylene.

17. The product for preventing biofouling of a substrate by a marine organism of claim 11, wherein the protective coating further comprises a marine coating.

18. The product of claim 11 for preventing fouling of a substrate by marine organismsWherein the imidazole-group-containing compound is medetomidine, and the metal oxide nanoparticles or SiO₂Nanoparticles of a metal oxide selected from the group consisting of CuO, ZnO, TiO₂、Al₂O₃And MgO, said SiO₂The nanoparticles are silica gel nanoparticles.

19. The product for preventing fouling of a substrate by marine organisms according to claim 18, wherein the metal oxide nanoparticles are CuO.

20. The product for preventing marine biofouling of a substrate according to claim 18, wherein the metal oxide nanoparticles are ZnO.