WO2014029013A1

WO2014029013A1 - Method for producing silver(i) orthoperiodates

Info

Publication number: WO2014029013A1
Application number: PCT/CA2013/000735
Authority: WO
Inventors: Patricia L. Nadworny; Graeme PROSPERI-PORTA; Kevin R. UNRAU
Original assignee: Innovotech, Inc.
Priority date: 2012-08-22
Filing date: 2013-08-22
Publication date: 2014-02-27

Abstract

The present invention relates to the synthesis of silver(I) orthoperiodates, preferably Ag₅IO₆. The synthesis process comprises mixing in an aqueous solution a hydroxide, a periodate, and a source of single valency silver ions; and allowing the silver(I) orthoperiodate to form.

Description

METHOD FOR PRODUCING SILVER(I) ORTHOPERIODATES

I. Field of the Invention

This invention relates to methods for producing anti-microbial silver compounds, preferably silver (I) periodates. The invention also includes the silver compounds produced by the process of the invention.

II. Background of the Invention

Silver and silver ions have long been known for their anti-bacterial properties. More recently, this use has extended to treating biofilms and to their incorporation as antimicrobial agents in medical devices and wound dressings.

As the new uses expand, there is a need for more efficient production processes and for the development of new silver-containing antimicrobial agents having improved properties, such as greater stability. There is also a need for antimicrobial compositions that overcome the settling and agglomeration problems of conventional oligodynamic compositions. There is also a need for antimicrobial compositions that are stable and are not readily inactivated in the environment of their intended use.

Processes for producing silver compounds are well known to those of ordinary skill in the art. See for example, Cohen and Atkinson, Inorg. Chem. 3(12) 1741 - 1743 (1964); and Balikungeri, et al, Inorganica Chimica Acta, 22:7-14 (1977).

III. Summary of the Invention

The compositions and methods of the present invention comprise one or more silver (I) periodate compounds or compositions, their methods of synthesis, and their use as antimicrobial agents. This invention provides several methods for producing or synthesizing Ag₅l0₆ and Ag₂H₃l06.

The compositions and methods of the present invention comprise silver ions or complexes containing silver as the antimicrobial agent. These silver-containing agents are the active agents in antimicrobial compositions. In preferred embodiments of the invention, the silver compounds are one or more silver (I) periodates.

The compositions and methods of the present invention have applicability wherever the presence of an antimicrobial agent is effective and/or beneficial. Without intending to limit the scope of potential uses, these antimicrobial agents may be used in a wide variety of agricultural, industrial, and medical environments, e.g., disinfecting any surface, particularly disinfecting work or processing surfaces (e.g., tables); in antimicrobial coatings; in medical devices and implants, particularly where having an antimicrobial property or characteristic would be beneficial; and in treating human, plant, and animal diseases and conditions. The compositions and methods of the present invention are also effective in treating and/or eradicating biofilm.

An advantage of the compositions and methods of the present invention is that the silver compounds are thermally stable and are not inactivated as quickly as typical ionic silver when placed in contact with compounds that typically inactivate silver ions, e.g., chlorides, sulphides, sulphates, carbonates, thiosulfates, bromides, and iodides. The compounds of the present invention also are not inactivated when exposed to a biological fluid, e.g., urine, feces, mucin, or blood. That is, the silver ions of the present invention retain their antimicrobial activity for periods of time in environments that would typically inactivate other silver containing agents.

IV. Detailed Description of the Invention

The present invention is a process for producing a silver (I) periodate comprising mixing in an aqueous solution a hydroxide; a periodate; and a source of single valency silver ions; and allowing the silver (I) periodate to form. In preferred embodiments of the invention, the hydroxide is potassium hydroxide, the periodate is potassium meta-periodate, or the source of silver is silver nitrate.

The compounds produced by the process of the present invention include, but are not limited to, a silver-containing chemical substance, compound, or complex that exhibits antimicrobial activity, and is Ag (I) combined with a higher oxidation state iodine and coordinated with oxygen atoms. Exemplary compounds include but are not limited to silver (I) periodate; one or more reaction products of a sodium and/or potassium diperiodatoargentate, each of these reaction products containing iodine; pentasilver hexaoxoiodate; Ag₅l0₆; silver orthoperiodate; silver periodate (VII); silver iodate (VII); 5 Ag₂0°l₂0₇; Ag₂H₃l0₆; and other combinations of Ag_xH_yl0₆ where x+y=5; Ag_xM_yl0₆, where the total cationic charge of x + y = 5 and M is one or more cations; and combinations thereof. One skilled in the art will readily recognize that the cation can be any of a large number of cations. Exemplary cations include but are not limited to K, Na, Mg, Ca, Au, Pt, Cu, Zn, and Fe. The preferred cations are K and Na.

The preferred compounds are Ag₅l0₆ and Ag₂H₃l0_6l and compositions containing one or both of these compounds.

In some embodiments of the invention, the compound may be anhydrous or a hydrate.

The compositions and methods of the present invention are antimicrobial, e.g. against biofilms, similar structures, or precursors formed by bacteria, fungi, viruses, algae, parasites, yeasts, and/or other microbes. In some embodiments of the invention, the antimicrobial effectiveness also applies to planktonic microorganisms. The invention also includes an improved process for producing silver compounds, including, but not limited to, the silver (I) periodate compounds of the present invention.

The silver (I) periodate compounds of the present invention may be produced by mixing, in an aqueous solution: 1) a hydroxide; 2) a source of iodine, e.g., a periodate; and 3) a source of silver. In preferred embodiments of the invention, the hydroxide is potassium hydroxide; the source of iodine is potassium meta-periodate; and the source of silver is silver nitrate. One skilled in the art will recognize that various types of water may be used in the processes of the present invention, including but not limited to deionized, reverse osmosis, distilled, double distilled, and milli-q. The preferred water is deionized or double deionized.

The silver (I) periodates of the present invention may be formed by mixing the primary ingredients in any ratio suitable for the specific reagents used and/or for the desired product, e.g., a ratio from about X:Y:Z to about X':Y':Z' (where X and X' is the relative amount of the source of silver; where Y and Y' is the relative amount of the hydroxide; and where Z and Z' is the relative amount of the source of iodine). X, X', Y, Y', Z, and Z' may be integers or any fraction of an integer.

For the production of 100% to near 100% pure Ag₅l0₆, where X:Y:Z is AgNO₃.KOH.KIO₄, the ratio may be from about 1 :8:2 to about 8:1 :0.5. The preferred ratio range is from about 1 :2.6:0.72 to about 7:2.5:1 , and the most preferred range is from about 1 :1.1 :0.4 to about 1.0.7:0.24.

As shown in Example 3, the inventors have found that 100% pure Ag₅l0₆ may be formed using 5.7 g AgN0₃, 5.1 g KOH, and 1.8 g KI0₄, which corresponds to a weight ratio of 1 :0.89:0.32.

The silver (I) periodates of the present invention may be formed by mixing: source of silver, from about 10 grams to about 80 grams; hydroxide, from about 10 grams to about 80 grams; and periodate, from about 5 grams to about 20 grams. One skilled in the art will recognize that the specific amounts used may be scaled up or down from these ranges together based on the amount of product intended to be produced.

In preferred embodiments of the invention, the silver (I) periodates of the present invention may be formed by mixing: source of silver, from about 25 grams to about 70 grams; hydroxide, from about 25 grams to about 65 grams; and periodate, from about 10 grams to about 18 grams.

In the most preferred embodiments of the invention, the silver (I) periodates of the present invention may be formed by mixing: source of silver, from about 40 grams to about 50 grams; hydroxide, from about 35 grams to about 45 grams; and periodate, from about 12 grams to about 16 grams. The amount of each raw material may be scaled up or down from the base quantity by multiplying each base quantity by a standard scale factor (SF). Base quantities that have been found to be effective are: silver nitrate, 45.6 g; potassium hydroxide, 40.8 g; potassium meta-periodate, 14.4 g; and De-ionized water, 250 ml_ It is intended that the present invention should not be limited to these specific amounts; they represent the relative proportions found to be effective using the least amount of silver nitrate in a process in which all of the silver reacted (for cost savings purposes).

This proportion also results in 100% purity product. One skilled in the art will recognize that changing one or more of the proportions may result in all of the silver reacting, but other side reactions may occur (e.g., KN0₃ formation). For example, decreasing the amount of KOH or KI0₄ may result in some of the AgN0₃ not reacting. The invention therefore includes other reactions, e.g., where purity of the resulting product and/or unreacted silver is acceptable.

One skilled in the art will readily recognize that other parameters typical of chemical reactions may variable depending on the specific reagents and the intended product(s). Exemplary other parameters include but are not limited to mixing time, stirring rate, temperature, pressure, drying time, and pH. It is believed that temperature and pressure may not be critical - room temperature and pressure have been shown to be effective in the synthesis processes shown in the Examples. The drying time and method may be related to the consistency of the final product - the final product may hold excess water if not well dried. With lower water volumes, the inventors have found stirring rate and time may affect the final grain size, e.g., a longer stirring time may result in larger grain size.

The inventors have also found that pH does not need to be controlled, and that varying the pH to achieve a desired product is well within the skill in the art. For example, if the process includes KOH and is a highly basic reaction, the typical product is Ag₅l0₆. If KOH is not present and the reaction is acidic/neutral, the product tends to be Ag₂H₃l0₆. If the pH is between these two, a mixture of Ag₅l0₆ and Ag₂H₃l0₆ tends to be produced.

The inventors have also found that a minimum stirring time is one that is sufficient to ensure that the reaction is complete, a time that is variable depending on the type and amount of reagents. Determining all of these parameters is well known to those with skill in the art.

Some embodiments of the invention include a source of single valency silver ions selected from the group consisting of silver nitrate; any silver compound soluble in aqueous solution; or combinations thereof. In some embodiments, the present invention relates to an article of manufacture which comprises the antimicrobial compositions of the present invention. In one embodiment, the composition is used to form an article or a portion of the article, for example by molding, casting, extruding, etc. Thus, at least part of the formed article is composed of one or more of the compositions of the present invention, alone or in admixture with other components. In another disclosed embodiment, the composition is applied to a preformed article or part of an article as a coating. The coated article may be produced, for example, by dipping the article into the composition or by spraying the article with the composition and then drying the coated article. In one preferred embodiment, the compositions are used to coat medical devices by reaction of one silver iodate (e.g. sodium diperiodatoargentate and/or potassium diperiodatoargentate) to form another (e.g. pentasilver hexaoxoiodate) in the presence of the device to be coated. In another preferred embodiment, the silver iodate is formed from silver nitrate, potassium hydroxide, and potassium meta-periodate in the presence of the device to be coated. In yet another preferred embodiment, the silver iodate is pre-synthesized as a powder using one of the above methods, and is then incorporated into or coated onto the device.

In some embodiments of the invention, the starting compounds used to form the silver iodates are produced by an aqueous solution of a monovalent silver salt or a silver complex such as silver nitrate, in the presence of a periodate such as potassium meta-periodate, with or without potassium hydroxide, depending on the desired silver iodate compound. Inclusion of the base causes formation of compounds such as Ag₅l0₆, while exclusion of the base causes formation of compounds such as Ag₂H₃l0₆. Alternately, silver iodates, such as pentasilver hexaoxoiodate, can be formed by hydrothermal reaction of compounds such as sodium or potassium diperiodatoargentate (III), or combinations thereof.

The reaction products of the present invention are typically formed in an aqueous solution. If formed from silver nitrate, potassium meta-periodate, and potassium hydroxide, this reaction can be performed at room temperature. If formed from potassium and/or sodium diperiodatoargentate (III), the reaction rate can be increased by heating the solution. While not intending to limit the invention to a particular temperature or temperature range, the reaction products of the present invention may be formed by heating the solution up to about 400°C, preferably in a range from about room temperature to about 150°C, preferably in a range from about 70°C to about 120°C. One skilled in the art will recognize that other factors, such as pressure, may affect the reaction, and may affect the choice of a particular temperature. For instance, the examples show that the reaction products of the present invention may be formed at 80°C under ambient conditions or may be formed at 120°C under pressure (e.g., in an autoclave).

The silver compositions of the present invention may be used with or incorporated into an article where antimicrobial properties are desirable and/or beneficial. The present invention also may provide compositions that provide antimicrobial, antibacterial, antiviral, or antifungal activity, or some combination thereof. Examples include, but are not limited to, medical and surgical devices and/or environments, such as catheters or implants. Other uses will be readily evident to those skilled in the art.

The methods and compositions of the present invention may be used wherever biofilm or similar structures may be found, including but not limited to microorganisms growing and/or floating in liquid environments, particularly flowing liquids.

Additional inactive ingredients may be optionally incorporated in the formulations, or added to the formulation, based on the intended use. Those skilled in the art will readily recognize that there are a wide variety of additional ingredients that may be added to a composition of the present invention, including but not limited to emulsifiers, thickening agents, solvents, anti-foaming agents, preservatives, fragrances, coloring agents, emollients, fillers, and the like.

Example 1

Operation #1

1. To a clean beaker on top of a magnetic stir plate, equipped with a magnetic stir bar (alternate: overhead stirrer), charge:

De-ionized water: 250 mL x SF = mL

2. Begin agitation of the water with the stirrer assembly.

3. Stirring rate: (e.g. 360 rpm)

(Stirring rate is a function of the batch size and stirrer. The operator may choose a stirring rate that causes the solution to generate a vortex and create an even mixture.)

4. Add 40.8 g x SF = g of potassium hydroxide.

5. Agitate the mixture until all the potassium hydroxide is dissolved.

6. Check the pH of the solution.

Operation #2

1. Add 14.4 g x SF = g potassium meta-periodate .

2. Agitate the mixture until all the potassium meta-periodate is dissolved.

3. Check the pH of the solution. Operation #3

1. Add 45.6g x SF = g silver nitrate to the solution.

2. A brown/black precipitate should form during this step. Operation #4

1. Mix for a minimum of 10 min (up to 2 hours or more can be used for larger scale batches).

2. Stop the magnetic stirrer.

If a larger volume of water is used, the following steps 3-5 are optional additional steps.

3. Allow the Ag₅l0₆ solids to settle for at least 2 hours before decanting. The mixture may be left for up to 24h. There should be no visible suspended particles present in the supernatant.

4. Using a peristaltic pump, decant at least ¾ of the solution.

5. Hold the decanted volume for disposal in Op #10.

Operation #5

1. Using filter paper P2 or equivalent in a Buchner funnel attached to a vacuum apparatus, filter the Ag₅l0₆. A small amount of ddH₂0 or deionized H₂0 can be used to wash the solid remaining in the bottom of the flask into the filter.

2. Measure the pH of the filtrate.

3. Hold the filtrate for disposal.

4. Slurry wash the Ag₅l0₆ solid cake on the filter with 200mL x SF = mL deionized or distilled water.

5. Add the wash water to the waste solution containing the filtrate (and decanted waste as appropriate) and hold for disposal.

Operation #6

1. Protecting the filter cake from collecting dust or other foreign objects (e.g. by covering the funnel with paper towel or equivalent), pull dry the filter cake by keeping the system under vacuum for approximately 15 minutes x SF = min. Seal any cracks or channels that form in the filter cake and break up any larger aggregates with a spoonula to assist removal of the water.

Note: The filter cake should be dried (e.g., pulled dry) until no more water comes through the filter and the cake appears relatively dry. This time may be variable, and is typically from about 15 minutes to about the time calculated in step 1. Note: This method should not result in any N0₃ in the final product. However, if the product shows signs of white crystal formation, the product should be washed with additional ddH₂0 and re-dried as described above. Operation #7

1. Transfer the Ag₅l0₆ solids to a large watch glass.

2. Cover the watch glass loosely with aluminum foil and place the watch glass in a fume hood to dry overnight. Operation #8

1. Weigh the overnight dried Ag₅l0₆.

2. Perform water content analysis on the overnight dried Ag₅l0₆.

3. If the material is sufficiently dry (average water content is≤ 7000 ppm), proceed to Op# 9.

4. If the water content in the material is >7000 ppm, break up any clumps, and transfer the material to an appropriate sized flask, .protected from light, and attach the flask to the vacuum pump (Configuration: sample-containing flask, then drying column, then neutralization trap, then vacuum pump).

5. Turn on the vacuum pump and allow the sample to dry under vacuum overnight (approximately 24 hours).

6. Transfer the dry product to a suitable (e.g. glass) tared, labeled container, place the container in a clean plastic (e.g. Ziploc) bag.

Operation #9

1. Perform water content analysis on the dried Ag₅l0₆.

2. Determine purity of the product by any appropriate test, e.g., XRD analysis.

Operation #10 ~ Waste Treatment

1. This step may be started while the product is drying.

2. Using pH paper or pH meter and appropriately diluted 65% nitric acid, neutralize the decanted solution to a pH between 6 and 8.

3. Discard neutralized solution down the drain.

Following this method, Ag₅l0₆ yields >95% are consistently achieved with a purity of 100% material being Ag₅l0₆ as determined by XRD. Example 2.

The purpose of this example was to determine whether Ag₅l0₆ synthesized from potassium or sodium diperiodatoargentate (III) and Ag₅l0₆ synthesized directly were of equivalent purity, and to compare their properties.

Methods Developed:

1. Ag₅l0₆ synthesis from sodium diperiodatoargentate (Method 1)

i. 4L of a 5000 ppm solution of sodium diperiodatoargentate in ddH₂0 was stirred on a magnetic heater/stirrer until dissolved.

ii. The solution was placed in an autoclave and a liquid cycle was run.

Alternatively, the solution can be heated in an oven at, for example, 80°C, at room pressure, but the process takes longer to provide the same material.

iii. The solid material formed via this method was processed as described below:

I. The solution was vacuum filtered using a fine glass crucible filter.

II. An additional 25 mL of ddH₂0 was added to the sample and drawn through to remove any soluble impurities.

III. The compound was dried under vacuum for 15 minutes.

IV. The sample was placed in a tared watch glass, placed in the fume hood, and covered, but not sealed and left to dry overnight.

V. Any large/hard lumps were broken up with a spoonula.

VI. The sample was transferred into a vial and the vial was stored in a sealed container with a desiccant.

iv. If the solutions after processing using the methods described above were not clear and colorless (i.e. there was visual evidence of silver compounds still present in the solutions), then, for some runs (2 and 3), the filtrate was re-autoclaved and re-processed to see if additional material could be recovered .

2. Ag₅l0₆ synthesis from potassium diperiodatoargentate

i. The same method was used as described in 1 .

Ag₅l0₆ direct synthesis (Method 2)

51 g of KOH was added to 1 L ddH₂0 and allowed to dissolve.

19g of KI0₄ were added to the solution, which was stirred at 360 rpm at

RT. iii. 5.7g of AgN0₃ was added to the solution, which was stirred at 360 rpm at RT for 2h.

iv. The solution was processed as described in Step iii of Method 1 (above). v. If the resulting product showed signs of white crystal formation (KN0₃), the product was washed with additional ddH₂0 and re-dried until no white crystals were observed.

Discussion/Conclusions/lmplications:

• All methods produced high purity Ag₅l0₆; however, the direct synthesis method produced at least three times higher yields than the other methods.

• The water content showed that there was between 10 and 200 molecules of Ag₅l0₆ per one molecule of water supporting the fact that Ag₅l0₆ is anhydrous when made by the above methods.

• While SEMs within each sample type looked similar, the Ag₅l0₆ made by each method was distinctly different in terms of physical shape/crystal structure. The direct method made large chunks with fibrous crystal protrusions while the autoclave methods made small crystals that had relatively homogeneous structures.

• Positive aspects of the direct method are that no intermediate compound needs to be made and the process can be completed at room temperature. Furthermore, the direct method yields at least twice the Ag₅l0₆ per molecule of silver used. KN0₃ impurities needed to be rinsed off with ddH₂0 to ensure a pure final compound with the ratios of material used in this example. It is possible to reduce NO₃ impurity formation by reducing the quantities of KOH and KI0₄ used to synthesize the Ag₅l0₆, as was shown in Example 1 , where 100% pure material was achieved.

Example 3.

Synthesis Optimization: The purpose of this study was to determine whether direct synthesis of Ag₅l0₆ could be performed with a lower starting concentration of base or KIO₄ relative to Example 2.

Run 1

1. 19g of KIO4 was added to 1 L ddH₂0 and allowed to dissolve.

2. The solution was stirred at 360 rpm at room temperature. The KI0 did not dissolve completely - the solution was filtered and 13.44g undissolved KI0₄ was collected. 3. 5.7g of AgN0₃ was added to the solution. The solution was stirred at 360 rpm at room temperature for 2 hours. The precipitate formed was a milky orange-brown color, and then turned light tan.

4. The solution was vacuum filtered.

5. An additional 25 mL of ddH₂0 was added to the sample and drawn through to remove any soluble impurities. A thin layer on top of the tan colored solids turned dark brown.

6. The compound was dried under vacuum for 15 minutes.

7. The sample was placed in a watch glass in the fume hood to dry overnight, and covered, but not sealed.

8. Any large/hard lumps were broken up with a spoonula.

9. If necessary, the product was washed with additional ddH₂0 and re-dried as described above until no white crystals were observed.

10. The sample was transferred to a vial and placed into a sealed container with a desiccant.

The product achieved in Run 1 was 97.4 wt% Ag₂H₃l0₆ (pale yellow product), and 2.6 wt% Ag₅l0₆ (dark brown product which formed on washing to a higher pH), as determined by XRD.

Run 2

1. The same method as Run 1 was used, except that 5.11g of KOH was dissolved in the ddH₂0 prior to adding the KI0₄. The KI0₄ took longer to dissolve than previous studies where 10x more KOH was used. After AgN0₃ addition, a dark brown precipitate formed immediately.

The product achieved in Run 2 was 75.6 wt% Ag₅l0₆ and 24.4 wt% unreacted KI0₄, as determined by XRD. In all cases, the yield was close to 100% of the theoretical yield.

Run 3 (performed in triplicate)

1. The same method as Run 2 was used, except that the KIO₄ was reduced to 1.82g, allowing it to dissolve quickly. After AgN0₃ addition, a dark brown precipitate formed immediately.

The product achieved (all three times) was 100% Ag_sl0₆ by XRD. Discussion/Conclusions/Implications:

• Run 1 showed that the formation of Ag₅l0₆ is dependent on the addition of KOH.

In its absence, Ag₂H₃l0₆ forms. The dissolution of KI0₄ also depended on the KOH.

· In Run 2, the KI0₄ in the final product showed that not all the KI0₄ reacted to form Ag₅l0₆.

• The adjusted method to synthesize Ag₅l0₆ in Run 3-1 to 3-3 resulted in pure Ag₅l0₆ with equal yield to the Ag₅l0₆ produced in Example 2. The reduction of KOH and KI0₄ from 51g to 5.1g and 19g to 1.8g, respectively, did not change the product purity or yield, while substantially reducing the cost of the reactants.

For future, it is recommended that the ratio of reagents used should be5.1 g KOH : 1.8g KI0₄ : 5.7g AgN0₃. In a separate study, it was determined that the stirring time could be reduced to 10 minutes without impacting the yield or purity.

Example 4

The purpose of this example is to determine whether Ag₅l0₆, currently synthesized following Example 1 , can be made using a lower starting volume of water.

The method that is used in Example 1 may use large volumes of water to generate the Ag₅l0₆. It was determined that significantly reducing the water volume resulted in the presence of KI0₄, one of the starting products, in the final product, due to its relatively low solubility. Although it initially dissolved at lower water volumes, it appeared that when the AgN0₃ was added to the solution, the higher ionic strength of the solution caused the KI0₄ to precipitate out before it had a chance to react with the AgN0₃. There did appear to be some room for reduction of the starting water volume, which would be very valuable for potential future commercial-scale production. The purpose of this study is to determine how much the starting water volume can be reduced (if at all) without impacting the purity of the final product.

1. A batch was generated following Example 1 at a scale factor of 1/5 (i.e. starting with 9.12g AgN0₃, etc.), but the water volume was reduced by an additional factor of 1/5

(i.e. 208 mL).

2. Based on the results of Step 1 , the water volume either was reduced or increased by an additional factor. For example, if, in Step 1 , a significantly quantity of impurities were present in the final product, then the additional scale factor was reduced based on how much impurities were present - e.g. if a small quantity of impurities were present, then a scale factor of 1/4 might be tried, whereas if a large quantity of impurities were present, then a scale factor of 1/3 or 1/2 might be tried. However, if the material was still 100% pure after Step 1 , then a scale factor of 1/6 or higher might be tried.

3. Step 2 was repeated with additional water volume scale factor changes as appropriate .

4. Once an additional scale factor for water volume was determined that appeared to be optimal in terms of the least water required while still generating an acceptable level of yield and purity in the final product, two more batches was generated to ensure consistency. At least one of these batches was generated at a larger scale, i.e. the base scale, to ensure that the process was scalable at the lower water content.

Batch 1— small scale as 1/5 of basic scale and the water volume with 1/25 (1/5*1/5) scale factor

In a clean 0.5 L beaker, 8.16 g of KOH was added to 200 mL ddH₂0. After KOH dissolved, 2.88 g of KI0₄ was added. The solution was stirred at 360 rpm. After KI0₄ dissolved, 9.12 g of AgN0₃ was added slowly. A brown precipitate immediately formed resembling Ag₅l0₆. The solution was stirred for 2 hrs. After that, the material was left to settle overnight to facilitate filtration. The next day, the solution was filtered with a crucible filter. The solid sample collected in the filter was washed with 40 mL ddH₂0. The sample was dried under vacuum for 15 min. During this period, the solid cake was smoothed with a spatula to close the tiny channels forming on the surface. The sample was transferred to a watch glass. This wet product was weighed as follow:

Watch glass: 131.03 g

Wet weight and watch glass: 140.26 g

Wet product: 9.23 g

The sample was left covered with aluminum foil in the fume hood to dry. After 2 day air-flow drying, the dried product was obtained as a dark brown powder. The water content of the dried product was measured. The results of the water content measurements are listed in the following table.

Table 1. Water content of samples in batch 1.

2 0.1002 7589.8

3 0.1005 6583.1

4 0.1007 5146.0

Average (ppm)^* - 6439.6

*The average of water content was calculated by the last three measurements

(2-4)

Watch glass + dry sample: 138.21 g

Dry sample: 8.18

Theoretical yield calculated for Ag₅l0₆ was 90% (8.21 g). Experimental yield was 99.6 %. The XRD data indicated that the sample was 100±0 wt% Ag₅l0₆.

Batch 2— small scale as 1/5 of basic scale and the water volume with 1/40 (1/5*1/8) scale factor

The results obtained for batch 1 indicated that the water volume scale factor could be reduced. Thus, in a clean 0.3 L beaker, 8.16 g of KOH was added to 125 mL ddH₂0. After KOH dissolved, 2.88 g of KI0₄ was added. The solution was stirred at 360 rpm. After KI0₄ dissolved, 9.13 g of AgN0₃ was added slowly. A brown precipitate immediately formed resembling Ag₅l0₆. The solution was stirred for 2 hrs. After that, the material was left to settle overnight in order to facilitate filtration. The next day, the solution was filtered with a crucible filter. The solid sample collected in the filter was washed with 40 mL ddH₂0. The sample was dried under vacuum for 15 min. During this period, the solid cake was smoothed with a spatula to close the tiny channels forming on the surface. The sample was transferred to a watch glass. This wet product was weighed as follow: Watch glass: 39.36 g; Wet weight and watch glass: 48.65 g; Wet product: 9.29 g.

The sample was left covered with aluminum foil in the fume hood to dry by air-flow overnight. The next morning, the dried product obtained was a dark brown powder. The water content of the dried product was measured. The results of the water content measurements are listed in the following table. Table 2. Water content of samples in batch 2.

2 0.1011 1124.6

3 0.1012 1169.0

Average (ppm) - 1158.7

Watch glass + dry sample: 47.04 g

Dry sample: 7.68 g

Theoretical yield calculated for Ag₅l0₆ was 90% (8.21 g). Experimental yield was 93.5 %. The XRD data indicated that the sample was 100±0 wt% Ag₅l0₆.

Batch 3— small scale as 1/5 of basic scale and the water volume with 1/50 (1/5*1/10) scale factor

The results obtained for batch 2 indicated that the water volume scale factor could be further reduced by an additional scale factor. In a clean 0.3 L beaker, 8.16 g of KOH was added to 100 mL ddH₂0. After KOH dissolved, 2.88 g of KI0₄ was added. The solution was stirred at 360 rpm. After KI0 dissolved, 9.12 g of AgN0₃ was added slowly. A brown precipitate immediately formed resembling Ag₅l0₆. The solution was stirred for 2 hrs. After that, the material was left to settle overnight. The next day, the solution was filtered with a crucible filter. The solid sample collected in the filter was washed with 40 mL ddH₂0. The sample was dried under vacuum for 15 min. During this period, the solid cake was smoothed with a spatula to close the tiny channels forming on the surface. The sample was transferred to a watch glass. This wet product was weighed as follow: Watch glass: 39.21 g; Wet weight and watch glass: 47.91 g; Wet product: 8.70 g

The sample was left covered with aluminum foil in the fume hood to dry by air-flow overnight. The next morning, the dried product obtained was as a dark brown powder. The water content of the dried product was measured. The results of the water content measurements are listed in the following table. Table 3. Water content of samples in batch 3.

2 0.1011 664.7

3 0.1004 802.8

Average (ppm) 758.4

Watch glass + dry sample: 46.69 g

Dry sample: 7.48 g

Theoretical yield calculated for Ag₅l0₆ was 90% (8.21 g). Experimental yield was 91.1%. The XRD data indicated that the sample was 100±0 wt% Ag₅l0₆. Batch 4— small scale as 1/5 of basic scale and the water volume with 1/100 (1/5*1/20) scale factor

The results obtained in run 3 indicated that the water volume for the reaction can be reduced even further. In a clean 0.125 L beaker, 8.16 g of KOH was added to 50 mL ddH₂0. After KOH dissolved, 2.89 g of KI0₄ was added. The solution was stirred at 360 rpm. After KI0₄ dissolved, 9.13 g of AgN0₃ was added slowly. A brown precipitate immediately formed resembling Ag₅l0₆. The solution was stirred for 2 hrs. After that, the material was left to settle overnight. The next day, the solution was filtered with a crucible filter. The solid sample collected in the filter was washed with 40 mL ddH₂0. The sample was dried under vacuum for 15 min. During this period, the solid cake was smoothed with a spatula to close the tiny channels forming on the surface. The sample was transferred to a watch glass. This wet product was weighed as follow: Watch glass: 39.20 g; Wet weight and watch glass: 48.99 g; Wet product: 9.79 g

The sample was left covered with aluminum foil in the fume hood to dry by air-flow overnight. The next morning, the dried product obtained was a dark brown powder. The water content of the dried product was measured. The results of the water content measurements are listed in the following table. Table 4. Water content of samples in batch 4.

2 0.1013 5253.7

3 0.1011 5024.7

Average (ppm) 5429.4

Watch glass + dry sample: 47.12g

Dry sample: 7.92 g

Theoretical yield of Ag₅l0₆ was 90% (8.21 g). Experimental yield was 96.4%. The XRD data indicated that the sample was 100±0 wt% Ag₅l0₆. Batch 5— small scale as 1/5 of basic scale and the water volume with 1/100 (1/5*1/20) scale factor

At this point it was decided that the water volume scale was low enough therefore reducing the water volume was not considered. For this batch, batch 4 was repeated to warranty consistency.

In a clean 0.125 L beaker, 8.16 g of KOH was added to 50 ml_ ddH₂0. After KOH dissolved, 2.89 g of KI0₄ was added. The solution was stirred at 360 rpm. After KI0₄ dissolved, 9.12 g of AgN0₃ was added slowly. A brown precipitate immediately formed resembling Ag₅l0₆. The solution was stirred for 2 hrs. After that, the material was left to settle overnight. The next day, the solution was filtered with a crucible filter. The solid sample collected in the filter was washed with 40 mL ddH₂0. The sample was dried under vacuum for 15 min. During this period, the solid cake was smoothed with a spatula to close the tiny channels forming on the surface. The sample was transferred to a watch glass. This wet product was weighed as follow: Watch glass: 39.36 g; Wet weight and watch glass: 48.67 g; Wet product: 9.31 g

The sample was left covered with aluminum foil in the fume hood to dry by air-flow overnight. The next morning, the dried product obtained was a dark brown powder. The water content of the dried product was measured. The results of the water content measurements are listed in the following table. Table 5. Water content of samples in batch 5.

2 0.1028 5287.0

3 0.1022 4761.3

Average (ppm) - 4962.7

Watch glass + dry sample: 47.08 g

Dry sample: 7.72 g

Theoretical yield of Ag₅l0₆ was 90% (8.21 g). Experimental yield was 94.0%. The XRD data indicated that the sample was 100±0 wt% Ag₅l0₆. Batch 6— basic scale on MOI and the water volume with 1/20 scale factor

Batch of Ag₅l0₆4 and 5 gave consistent results of 100% purity (XRD) and yields of 94-96.4%, indicating that the water volume factor of 1/20 did not have a negative impact on the purity and yield of Ag₅l0₆ production. For this particular batch, a large scale was generated to ensure that the process was scalable with 1/20 water volume factor.

In a clean 0.5 L beaker, 40.8 g of KOH was added to 250 mL ddH₂0. After KOH dissolved, 14.41 g of KI0₄ was added. The solution was stirred at 360 rpm. After KI0₄ dissolved, 45.6 g of AgN0₃ was added slowly. A brown precipitate immediately formed resembling Ag₅l0₆. The solution was stirred for 2 hrs. After that, the material was left to settle overnight. The next day, the solution was filtered with a crucible filter. The solid sample collected in the filter was washed with 40 mL ddH₂0. The sample was dried under vacuum for 15 min. During this period, the solid cake was smoothed with a spatula to close the tiny channels forming on the surface. The sample was transferred to a watch glass. This wet product was weighed as follow: Watch glass: 131.34 g; Wet weight and watch glass: 182.6 g; Wet product: 51.26 g

The sample was left covered with aluminum foil in the fume hood to dry by air-flow overnight. The next morning, the dried product obtained was a dark brown powder. The water content of the dried product was measured. The results of the water content measurements are listed in the following table. Watch glass + dry sample: 171.92 g; Dry sample: 40.58 g

Theoretical yield calculated for Ag_sl0₆ was 90% (41.04 g). Experimental yield was 98.9 %. The XRD data indicated that the sample was 100±0 wt% Ag₅l0₆.

Table 6. Water content of samples in batch 6.

2 0.1019 3102.1

3 0.1024 2873.0

Average (ppm) 3057.0

During the reactions, the pH of the solution in all of batches 1-6 was higher than 14 at all times. The step of decanting supernatant described in MOI was not considered because the water volume was too low to be decanted. The water content of Ag₅l0₆ obtained in batch 2 and 3 were lower in comparison to the other batches.

The table below showed a comparison of purity, yield and crystallite size of final product (Ag₅l0₆) obtained from each batch.

Table 7. Purity, yield, and crystallite size of Ag₅l0₆ from each batch.

From batch 1 to 5, Ag₅l0₆ was generated at a scale factor of 1/5 with an additional water volume scale factor. In batch 1 , the water volume factor was 1/5^*1/5. Ag₅l0₆ was obtained in 100% purity and 99.6 % yield. This result showed that further reduction of the water volume could be considered. In the batches 2 and 3, the water volume scale was reduced consecutively. The additional water volume scale factors 1/8 and 1/10 were applied respectively. The purity of Ag₅l0₆ for both batches was 100% and the yields were 93.5% and 91.1 % respectively. Encouraged by these results, the water volume was further reduced with 1/20 volume factor. Ag₅l0₆ produced in this batch had a purity of 100% and a yield of 96.4%. In fact, the water volume can be reduced further. But 1/20 scale factor was enough to satisfy the scale-up production. Batch 5 (repeated as per batch 4) produced Ag₅l0₆ with 100% purity and a yield of 94.0%. These results were similar to the one obtained in batch 4. This indicated that the water volume scale factor of 1/20 did not have a negative impact on the purity and yield of the product for small scale.

For batch 6, Ag₅l0₆ was scaled-up with the water volume scale factor determined in batch 4 and 5. The batch 6 gives Ag₅l0₆ with 100% purity and 98.9% yield. This demonstrated that reducing water volume to 1/20 scale factor resulted in pure Ag₅l0₆ with equal yield to the one produced with original water volume.

Although the water volume can be reduced without impacting the purity and yield of the final product in this study, it is observed that the crystallite size increased slightly. The crystallites sizes of Ag₅l0₆ derived from experiments with original volume are in the range of 12 A to 29 A whereas the ones generated using a lower water volume factor in the reaction produced slightly bigger crystallites sizes (Table 7). As for now, there is no evidence indicating that increasing the crystallite sizes of Ag₅l0₆ may differ in its ongoing and future applications.

In summary, these results proved that the water volume can be reduced to 1/20 of the original volume based on MOI without negatively impacting the purity and yield of Ag₅l0₆; improving the commercial-scale value of Ag₅l0₆ production in the future.

Example 5

Dressings Coated

• Gauze sponges - 100% cotton

• 3-ply dressings - rayon/polyester core with upper and lower HDPE layers

· Tensoplast™ - rayon/cotton with adhesive

Coating Methods

1. Coating During Synthesis of Ag₅l0₆ from sodium diperiodatoargentate(lll)

A. 500 mL of a 5000 ppm solution of sodium diperiodatoargentate was made in ddH₂0 and stirred on a magnetic heater/stirrer until the sodium diperiodatoargentate had dissolved. B. 1 in² pieces of dressing (or larger, as appropriate) were aseptically cut and suspended in the solution with the use of string or the dressing's adhesive.

C. The solution was placed in an autoclave and a liquid cycle was run.

D. After autoclaving, the dressing pieces were removed from the solutions aseptically using forceps and were allowed to drip back into the solution for 30 seconds.

E. The dressing pieces were placed on watch glasses in the fume hood (under aluminum foil) until dry.

F. The dressing pieces were stored in sealed glass containers protected from light, and kept cold, until they were used.

2. Coating During Direct Synthesis of Ag₅l0₆

A. 51 g of KOH was added to 1L ddH₂0 and allowed to dissolve.

19g of KIO4 was added to the solution. The solution was stirred at 360 rpm at RT.

B. 1 in² pieces of dressing (or larger, as appropriate) were aseptically cut and placed in the solution, suspended using string, or the dressing's adhesive.

C. After the KI0₄ was dissolved completely, 5.7g of AgN0₃ was added to the solution. The solution was stirred at 360 rpm at room temperature for approximately 3 hours.

D. The dressing pieces were removed from the solutions, dried and stored as described in 1.

E. If KNO3 appeared to have formed on the dressings (white crystals) after drying, the dressings were briefly dipped in ddH₂0 and re-dried as described in 1.

Note: For some dressings, the dressings were dipped prior to drying to remove KNO₃, while for other dressings, the dressings were dipped as described in E. 3. Incorporation into Dressings Post-Synthesis

A. 5g of previously made Ag₅l0₆ was ground to a fine powder using a mortar and pestle (or equivalent, e.g. Spex machine) and then added to 1L ddH₂0. The slurry was stirred at approximately 360 rpm.

B. 1in² pieces (or larger, as appropriate) of dressing were aseptically cut. The pieces were placed or suspended (using string or the dressing's adhesive) in the slurry for 15 minutes at room temperature (or longer - up to 2 or 3 hours as appropriate) with stirring (e.g. with a magnetic stirrer on a heater/stirrer).

C. If large chunks of Ag₅l0₆ formed during stirring, they were broken up (e.g. with a spoonula) so that they slurried properly.

D. The pieces were then removed from solution using clean forceps, dried, and stored as described in Method 1. Discussion/Conclusions/Implications

• Of the coating methods, the autoclave method was the least effective - the 3 ply dressings did not coat adequately to generate zones of inhibition, while the zone size dropped with time for the gauze dressing. The remaining methods all generated dressings with comparable silver contents that made consistent zone of inhibition sizes for 10 days, at which point the study was ended, indicating excellent bacteriostatic longevity. In all cases, the only silver compound present on the dressings was Ag₅l0₆.

Example 6.

We have also coated metals and beans using variations on the process described above, as appropriate to the specific materials. For the metals, we put the metal pieces in a round bottomed flask and used an overhead stirrer, but otherwise the method was the same. For the beans, we made a slurry of Ag₅l0₆ in water, injected a portion of it with the beans in a Falcon tube, and then closed the Falcon tube, and spun the beans around until they were coated.

We obtained coated metals and coated beans, both of which were shown to exhibit anti-microbial activity stemming from the coating.

While the invention has been described in some detail by way of illustration and example, it should be understood that the invention is susceptible to various modifications and alternative forms, and is not restricted to the specific embodiments set forth in the Examples. It should be understood that these specific embodiments are not intended to limit the invention but, on the contrary, the intention is to cover all modifications, equivalents, and alternatives falling within the spirit and scope of the invention.

Claims

IN THE CLAIMS: We claim:

1. A process for producing a silver (I) periodate comprising mixing in an aqueous solution a hydroxide; a periodate; and a source of single valency silver ions; and allowing the silver (I) periodate to form.

2. The process of claim 1 wherein the hydroxide is potassium hydroxide, the periodate is potassium meta-periodate, or the source of silver is silver nitrate.

3. The process of claim 1 wherein the silver (I) periodate that is formed is selected from the group consisting of pentasilver hexaoxoiodate; Ag₅l0₆; silver orthoperiodate; silver periodate (VII); silver iodate (VII); 5 Ag₂0°l₂0₇; Ag₂H₃l0₆; and other combinations of Ag_xH_yl0₆ where x+y=5; Ag_xM_yl0₆, where the total cationic charge of x + y = 5 and M is one or more cations; and combinations thereof.

4. A process for synthesizing a silver (I) periodate comprising dissolving a hydroxide in water; adding a meta-periodate and stirring the resulting solution; adding a source of silver ions, and stirring the resulting slurry; and drying the filtered product, thereby producing a silver (I) periodate powder.

5. A method for coating a surface with at least one antimicrobial compound or complex comprising synthesizing a material of claim 2 following a process such as claim 4 in the presence of the surface, thus causing the material to coat onto or be incorporated into the surface.

6. The process of claim 5 wherein the surface is one or more surfaces selected from the group consisting of wound dressings, metals, plants or plant parts, seeds, medical devices, medical instruments, and veterinary devices and instruments.

7. A method of coating a surface with at least one antimicrobial compound or complex of claim 2 comprising first synthesizing the material of claim 2 following a process such as claim 4, and then contacting the formed material with the surface, thus causing the material to coat onto or be incorporated into the surface.

8. The process of claim 1 wherein the process produces a silver compound having a purity up to about 100% pure.

9. The process of claim 1 wherein the process yields from about 95% to about 100% silver compound.

10. The process of claim 1 wherein the source of silver ions, the hydroxide, and the periodate are mixed in a ratio from about X:Y:Z to about X':Y':Z' (where X and X' is the relative amount of the source of silver; where Y and Y' is the relative amount of the hydroxide; and where Z and Z' is the relative amount of the source of iodine). X, X', Y, Y', Z, and Z' may be integers or any fraction of an integer.

1 1. The process of claim 10 for the production of Ag₅l0₆, where the ratio is from about 1 :8:2 to about 8:1 :0.5.

12. The process of claim 11 for the production of Ag₅l0₆, where the ratio is from about is from about 1 :2.6:0.72 to about 7:2.5:1.

13. The process of claim 1 1 for the production of Ag₅l0₆, where the ratio is from about is from about 1 :1 .1 :0.4 to about 1 : 0.7:0.24.

14. The process of claim 1 1 for the production of pure Ag₅l0₆, where the ratio is 1 :0.89:0.32.

15. The process of claim 1 for the production of pure Ag₅l0₆, where uses 5.7 g AgN0₃, 5.1 g KOH, and 1.8 g KI0₄.

16. The process of claim 7 wherein the surface is one or more surfaces selected from the group consisting of wound dressings, metals, plants or plant parts, seeds, medical devices, medical instruments, and veterinary devices and instruments.