GB2440332A

GB2440332A - Polymer-metal complexes

Info

Publication number: GB2440332A
Application number: GB0614613A
Authority: GB
Inventors: George Andrew Francis Roberts
Original assignee: Individual
Current assignee: Individual
Priority date: 2006-07-22
Filing date: 2006-07-22
Publication date: 2008-01-30
Also published as: WO2008012514A1; GB0614613D0

Abstract

A process for producing polymer-metal complexes comprises (i) contacting a metal salt solution with a polymer to form a polymer-metal ion complex, wherein the polymer and polymer-metal ion complex are in the solid phase, (ii) optionally dissolving the polymer-metal ion complex, and (iii) chemically reducing metal ions in the polymer-metal ion complex to form the polymer-metal complex. The solid phase comprises / 25 wt.% of the polymer and/or the polymer is in the form of a powder or flake. The polymer may be chitin, chitosan, alginate, polyvinylamine, carboxymethylcellulose, or hyaluronic acid. The metal salt may comprise silver, copper, gold, palladium, platinum, and/or tin. A polymer-metal complex in solution, which is translucent and free of suspended, particulate metal-containing species is also disclosed. A solid premix comprising a polymer-metal complex and a solid reducing agent and use of a reductone to reduce a polymer-metal ion complex to a polymer-metal complex are further claimed.

Description

S

1 2440332

PROCESS

The present invention relates to a process for the production of a polymer-metal complex.

Combinations of certain metals with polymers have shown considerable potential for use as bioactive materials and/or for their catalytic applications. US 5817325 and US 5849311, for example, provide examples of antimicrobial articles, devices and formulations prepared by applying an organic coating to a substrate followed by immersing the coated substrate in a solution of silver or potassium salt.

However, in many of the polymer-metal combinations disclosed in the prior art, the metal is present in its ionic state as part of either an inorganic or an organic salt. The use of polymer-metal combinations in this form presents a number of problems, for example there is limited control over the release of the metal ions, which results in a rapid decrease in its effectiveness and, in the case of biomedical applications, there is the possibility of excess metal ions entering the body.

Further, in the case of silver, staining of the skin on contact with silver ions and a change in colour of the material due to gradual photoreduction of the silver ions are additional problems.

These problems have been overcome by reducing the metal ions to form polymer-metal complexes. In this respect several processes have been disclosed in the prior art, see, for example, JP 04 002877 and JP 03 045709, which describe the production of metal colloids by chemically reducing water-soluble salts of copper, lead, silver or tin in an aqueous solution containing a water-soluble polymer, or a mixture of watersoluble polymers thereof.

WO 00/492 19 discloses a process for treating a substrate to impart biocidal properties. The process comprises the steps of depositing or impregnating the substrate with solubilised chitosan, immersing the substrate in a solution of a silver salt and reducing the silver salt to atomic/metallic silver. Likewise, WO 02/15698 and EP-A-l3 12262 also describe the preparation of articles or powders, respectively, having contact biocidal properties.

There remains a need for improved processes for producing polymer-metal complexes and to improved polymer-metal complex products.

In a first aspect of the present invention, there is provided a process for producing a polymer-metal complex comprising the steps of: (i) contacting a solution comprising one or more metal salts with a polymer which is capable of interacting with the metal salt to form a polymer-metal ion complex and wherein the polymer and the polymer-metal ion complex are in the solid phase, said solid phase comprising the polymer in an amount of at least 25% by weight andlor being in the form of a powder or flake; (ii) optionally dissolving the polymer-metal ion complex; and (iii) chemically reducing metal ions in the polymer-metal ion complex to form the polymer-metal complex.

In a second aspect, the invention also provides the product obtainable by the process of the first aspect of the present invention.

In a third aspect, there is provided a polymer-metal complex in solution, which is translucent and free of suspended particulate metal-containing species. Thus, preferably, the solution contains no colloidal and/or suspended particles.

In a fourth aspect, there is provided a solid premix comprising a polymer-metal ion complex and a solid reducing agent.

In a fifth aspect, the invention provides a process for the production of a polymer-metal complex comprising the steps of: (a) contacting an aqueous solution comprising one or more metal salts with a solution comprising a]ginic acid or a salt thereof, polyvinylanune or a mixture thereof, (b) treating the solution in (a) with a gelling agent to form a gel; and (c) chemically reducing metal ions in the gel, wherein (b) and (c) may be carried out simultaneously or sequentially in any order.

in a sixth aspect, the invention provides the use of a reductone for reducing a polymer-metal ion complex to a polymer-metal complex.

The polymers useful in the process of the present invention, and which may be employed in step (1), preferably comprise functional groups selected from amine, carboxylic acid, carboxylate or hydroxyl, and mixtures thereof; and may be natural or synthetic polymers. For example, the polymer may be selected from the group consisting of chitin, chitosan and polyvinylamine, poly(ethylene imine), poly(lysine), cationic' polyacrylaniide copolymers, cellulose that has been denvatised to incorporate amine groups, alginate, hyaluronic acid, carboxymethyl cellulose, and polymers and copolymers containing acrylic acid and similar monomers. Most preferably, however, the polymer used in step (i) comprises amine functional groups and is selected from the group consisting of chitin, chitosan and polyvinylamine. Particularly preferred polymers are chitin and chitosan.

Chitin is a natural polymer found in the exoskeleton of crustaceans, the internal pen of squid, and the cell wall of a number of fungi. It is most commonly used after conversion to chitosan by a deacetylation treatment. Although chitosan may be obtained directly from certain fungi, almost all commercial chitosan is currently obtained from crustacean-derived chitin. However, chitin and chitosan from fungal sources are gradually becoming available in commercial quantities.

The teims chitin' and chitosan' do not refer to discrete and distinct polymers but to a range of structurally closely related polymers differing in the ratio of D-glucosamine and N-acetyl-D-glucosazmne residues. Chitins normally contain from 5-10% D-glucosainine residues and all chitosans, unless specially prepared by techniques involving multiple deacetylation processes, contain a proportion of N-acetyl-D-glucosamine residues.

The polymer used in step (i) of the process is a solid and is preferably in the form of a powder or flake. The solid phase typically comprises the polymer in an amount of at least 25%, preferably at least 30%, such as at least 40% or at least 50% by weight, more preferably at least 60% by weight, such as at least 70% or at least 80% or at least 90% by weight. The polymer is typically not in the form of a coating applied to a substrate.

S

The process steps (i), (ii) and (iii) may independently be carried out at any temperature, such as a temperature between room temperature and an elevated temperature (i.e., above room temperature) such as at a temperature of 25 to 95 C, more preferably at a temperature of 45 to 90 C, such as 60 to 90 C or 70 to 90 C, most preferably at a temperature of 80 to 90 C. Preferably, step (i) is carried out at elevated temperatures, as described above. Most preferably, step (i) is carried out at a temperature of 80 to 90 C and the subsequent steps (ii) and (iii) are carried out at room temperature. The term room temperature' as used herein has its ordinary meaning and typically ranges from 21 to 25 C. It has surprisingly been IS found that carrying out step (i) at elevated temperatures increases the stability of a subsequently formed solution of polymer-metal complex.

Without wishing to be bound by theory, it is believed that during step (i), metal ions in the solution are adsorbed, complexed or otherwise associated onto the polymer to form a polymer-metal ion complex. Typically, adsorption takes place at specific sites of the polymer substrate, for example, on the amine groups which may act as ligands and bind directly with the metal ions. Another suitable site for adsorption of the metal ions onto the polymers includes carboxylate groups, where the counter ion, which is usually a sodium, potassium or animoniuin ion, can be exchanged for the metal ions in solution. In this case, the binding may be through ionic/electrostatic forces or co-ordination bonds or a combination of these two mechanisms.

Step (i) is preferably performed to the stage of complete absorption, i.e., either when all of the metal ions in solution have been adsorbed onto the polymer or when the polymer is saturated and no more metal ions can be adsorbed. However, it will be appreciated that the rate of adsorption, and consequentially the time taken for complete adsorption, may vary depending on the temperature and other process variables used, such as the concentration of the metal salt solution.

Although the solution of one or more metal salts in step (i) can be of any concentration, higher concentrations are preferred.

If not all of the metal ions in solution have been adsorbed onto the polymer during step (i), the polymer-metal ion complex produced may be filtered off and subsequently washed to remove any excess metal salts. This may be carried out in the same solvent for the solution used in step (i), without the metal salts dissolved therein.

The amount, by weight of polymer, of metal ions that is preferably used in step (i) of the process ranges from 0.1 to 20 %, such as 1 to 20%, more preferably from 2 to 15 %, such as 2.5 to 10 %, most preferably from 3 to 8 %.

The one or more metal salts are preferably selected from the salts of silver, copper, gold, palladium, platinum and tin, and mixtures thereof. Silver salts are preferred.

Preferably, the one or more metal salts are present in an aqueous solution, in which case the metal salts must be water-soluble to some extent. Most preferably, the metal salt is silver nitrate. The term aqueous solution as used herein describes a solution in a solvent comprising at least 5%, such as at least 10%, preferably at least 25%, such as at least 50% or at least 75%, most preferably at least 95% such as at least 99% or even 100%, by weight of water.

In an alternative embodiment, the one or more metal salts may be present in a non-aqueous solution, such as a solution of the one or more metal salts in an anhydrous polar organic solvent e.g., a C1-C6 alcohol such as ethanol, methanol or isopropyl alcohol.

The polymer-metal ion complex formed in step (i) may be dissolved in step (ii), preferably at a pH below 6.5, before the metal ions are subjected to chemical reduction in step (iii). Suitable acids for carrying out step (ii) include but are not limited to organic acids, such as, for example, acetic acid, lactic acid, glutamic acid and glycolic acid.

Although, in one embodiment of the invention, step (i) is limited to contacting a solution comprising one or metals salts to a polymer wherein the polymer and the polymer-metal ion complex produced remain in the solid phase, it will be appreciated that the formation of polymer-metal ion complexes can also be achieved if the polymer is present as part of a solution in step (i). In this case, the resulting polymer-metal ion complex remains in solution and step (ii) of the process is made redundant.

Therefore, the present invention also contemplates a process for the production of a polymer-metal complex comprising the steps of: (I) contacting a solution comprising one or more metai salts with a polymer which is capable of interacting with the metal salt to form a polymer-metal ion complex and wherein the polymer and the polymer-metal ion complex are in solution; and (II) chemically reducing metal ions in the polymer-metal ion complex to form the polymer-metal complex.

Particularly preferred polymers for use in step (I) include water-soluble polymers, such as, for example, polyvinylamine, alginic acid or a salt thereof, carboxymethyl cellulose or a salt thereof, hyaluronic acid or a salt thereof, poly(ethylene imine) or mixtures thereof. However, polymer substrates which require a pH of below 6.5 in order to dissolve in the solution comprising one or metal salts in step (I) are also encompassed in this embodiment of the invention. A pH of below 6.5 may be achieved by the addition of, for example, an organic acid such as acetic acid, lactic acid, glutamic acid or glycolic acid.

Chemical reduction of the polymer-metal ion complex in the process of the invention may be camed out using any suitable reducing agent. Preferably, however, chemical reduction is carried out using a reductone, such as ascorbic acid or a salt thereof, which are more preferably non-toxic and readily available.

As used herein, the term reductone includes compounds containing an enediol structure stabilised by conjugation and hydrogen bonding with an adjacent group, RC(OH)C(OH)C(=O)R'. Preferably R and R' are the same or different and are selected from: hydroxyl; C1 to C20 alkyl, optionally substituted with C, to C3 alkyl, hydroxyl or C12 to C24 acyloxy; and R and R' may be linked to form a ring structure. Reductones are commonly derived from saccharides by oxidation at the carbon atom alpha to the carbonyl functionality. Ascorbic acid and its salts are the S preferred reductones, used alone or in combination. Suitable salts of ascorbic acid include food grade salts (such as, for example, sodium, potassium or calcium salts).

It will be appreciated that chemical reduction may be performed on polymer-metal ion complexes, which are either in the solid phase or in solution. For example, if the polymer-metal ion complex is in the solid phase (e.g., if step (ii) is omitted from the process), chemical reduction of metal ions may be carried out on the solid polymer-metal ion complex or the polymer-metal ion complex may be dissolved to form a solution prior to the step of chemical reduction.

Since ascorbic acid aids the dissolution of certain polymer substrates, such as chitosan., the use of ascorbic acid as the reducing agent may form part or all of the acid required to perform steps (ii) and (iii) of the process, simultaneously.

The molar ratio of reducing agent to metal ions in the polymer-metal ion complex in the chemical reduction step is preferably from 2:1 to 1:2.

During the chemical reduction step (i.e., step (iii) or step (II)), metal ions in the polymer-metal ion complex are reduced. Preferably, the metal ions are reduced to metallic atoms to form a polymer-metal complex. Preferably, the product of the chemical reduction step comprises more than 0.1% by weight of metal in the polymer-metal complex, more preferably more than 0.5%, such as more than 1.5%, most preferably more than 3.5%, such as more than 6% or more than 10% or more than 15%. Typically, the product contains less than 50%, such as less than 25%, by weight of metal in the polymer-metal complex.

If step (ii) is omitted, the polymer-metal complex formed in step (iii) may be in solid form. This solid can be filtered off, washed and dried. Washing may be carried out using an aqueous solution. Alternatively or subsequently, the solid S 8 polymer-metal complex may be dissolved at a pH below 6.5, using the same acids mentioned above in relation to step (ii).

Solutions of polymer-metal complex produced by the present invention may be treated to precipitate out the polymer-metal complex (e.g., by neutralising the solution), which can then be washed using an aqueous solution and subsequently dried. Alternatively, the solution of polymer-metal complex is spray dried to form solid polymer-metal complex in the form of a free flowing powder.

The polymer-metal complexes produced by the present invention may be used in sprays or aerosols, or used as a coating material, or formed into fibres, films, foams, freeze-dried mats, gels, hydrogels or sponges. In addition, the polymer-metal ion complexes may also be used as a coating material, or formed into fibres, films, solid foams, freeze-dried mats, gels, hydrogels or sponges prior to the chemical reduction step.

It has surprisingly been found that solutions of the polymer-metal complex produced by the process according to the invention are typically homogeneous solutions. Whereas polymer-metal ion complexes show negligible absorption across the visible spectrum, chitosan-silver complexes formed by the process as described above, in relation to the first aspect of the invention, show a strong absorption band in the region 400-420 mn. The extinction coefficient for polymer-metal complexes, measured in a 1 cm cell, based on the molar concentration of silver present, is preferably greater than 10,000 L mol' cnf'.

In order to improve the clarity and/or the shelf-life (stability) of the solutions produced by the process of the present invention a polymer-compatible surfactant may be added before or after steps (ii) or (iii), and before or after step (II). For example, cationic and non-ionic surfactants may be used in conjunction with chitosan and other polymers that are positively charged in solution, while anionic and non-ionic surfactants may be used in conjunction with alginate and other anionic polymers.

Thus, in a preferred embodiment of foe process, prior to the step of chemically reducing metal ions in the polymer-metal complex, the polymer-metal ion complex may be contacted with a surfactant, preferably, a quaternary animonium compound, such as a quaternary ammonium compound having an alkyl chain of from 6 to 24 carbon atoms, for example cetyl trimethylammonium bromide. The addition of such a compound surprisingly produces a solution which, after chemical reduction and, if required, dissolution of the polymer-metal complex, is less coloured than solutions otherwise produced.

Depending on the intended use, it may be desirable to insolubilise the resulting polymer-metal complex by cross-linking or other means known in the art. In order to maintain the solubility characteristics of the polymer in the resulting polymer-metal complex, preferably, no cross-linking or equivalent step is perfonned.

The present invention also provides a polymer-metal complex in solution, which is translucent (i.e., typically non-opalescent) and free of suspended particulate metal-containing species. This solution has unexpectedly been found to be produced by the invention. Preferably, the solution is a clear (i.e., transparent) solution.

The present invention also provides a solid premix. By the term solid premix, it is meant a mixture or blend of two or more components in the solid phase.

Preferably the premix is in the form of a powder.

The polymer-metal ion complex contained in the solid premix may be produced according to step (i) of the process, as described above. However, it is also contemplated that the polymer-metal ion complex may be produced according to step (I). In this latter case, the resulting solution of polymer-metal ion complex is treated to obtain the polymer-metal ion complex in the solid phase. This may be achieved using any suitable technique known in the art but is preferably performed by spray drying or a method used to induce precipitation of the solid out of solution. *1

The solid premix comprises a solid reducing agent. Preferably, the reducing agent is acidic, such as, for example, solid ascorbic acid or a salt thereof or mixtures thereof. Additionally, the premix may further comprise a solid acid such as glycolic acid, in addition to the polymer-metal ion complex and reducing agent.

S Since ascorbic acid acts as a reducing agent and aids the dissolution of certain polymer substrates (e.g., chitosan), the use of a solid acid in addition to the polymer-metal ion complex may be omitted if ascorbic acid is used as the reducing agent. It will be appreciated that if ascorbic acid is used as both a reducing agent and solubilising agent, the ascorbic acid is preferably present in a higher concentration than if it were acting solely as a reducing agent.

One advantage of forming a premix that is solid is the ease with which it can be transported and handled. By subsequently dissolving the solid premix, the metal ions in the polymer-metal complex can be reduced, when required. Another advantage is the greater storage life of the product in premix form compared with the storage life of the product in solution form. Also, providing the product in premix form provides greater versatility as the user may readily produce solutions of varying concentrations from the same batch of solid premix.

According to the process of the fifth aspect of the present invention, steps (b) and (c) may be carried out simultaneously. Therefore, the process may comprise, after step (a), contacting the product formed in (a) with an agent, such as calcium ascorbate, that causes both gelling and chemical reduction to take place.

Alternatively, steps (b) and (c) may be carried out sequentially and in either order, i.e., step (b) may be carried out before step (c) or, alternatively, step (c) may be carned out before step (b).

Suitable salts of alginic acid include sodium, calcium, potassium, magnesium and mixtures thereof. Preferably, sodium alginate is used in step (a).

The gelling agent used in step (b) preferably comprises calcium ions. Suitable gelling agents used in step (b) preferably include any water-soluble salt of calcium, such as calcium ascorbate.

The aqueous solution compri sing one or more metal salts in step (a) may be selected from the salts of any metal but are preferably selected from the salts of silver, copper, gold, palladium, platinum and tin, and mixtures thereof.

During step (a), metal ions are adsorbed, complexed or otherwise associated onto the alginic acid or salt thereof and/or the polyvinylamine to form an alginate/polyvinylamine-metal ion complex as described above in relation to step (i).

Chemical reduction of metal ions in the gel may be carried using any suitable reducing agent; however, the use of a reductone is preferred, in particular ascorbic acid or a salt thereof.

The present invention also provides the use of a reductone for reducing a polymer-metal ion complex to a polymer-metal complex. Preferably, the metal ions are reduced to metal atoms. In the preferred embodiment, the reductone is preferably ascorbic acid or a salt thereof. It will be appreciated that the use of a reductone for reducing polymer-metal ions can be carried out as described above in relation to step (iii), step (II) or step (c) of the processes contemplated by the present invention.

The products prepared by the processes of the present invention may be used as bioactive materials, particularly in the biomedical and/or healthcare fields. Also, due to the extremely reactive nature of the metal in the polymer-metal complexes these products can be used as catalysts in a number of chemical and/or biochemical processes.

Examples

Example I

g of finely ground chitosan particles was stirred in 70 ml deionised water. 0.6 g AgNO3 in 5 ml deionised water was added drop wise into the chitosan *1 suspension. The chitosan suspension was stirred until the supernataiit did not give any precipitate on addition to a solution of NaCI. The suspension was then diluted to 970 ml with deiomsed water and 9 ml lactic acid (80%) was added to solubilise the chitosan/Ag complex. Once a homogeneous solution was obtained a solution of 0.9 g ascorbic acid in 20 ml deionised water was added. A strong yellow-brown colour developed rapidly and full reduction was achieved within I hour.

Example 2

10 g of finely ground chitosan particles was stirred in 70 ml deionised water while 0.6 g AgNO3 in 5 ml deionised water was added drop wise to it. The suspension was stirred until the supernatant did not give any precipitate on addition to a solution of N'aCl. The suspension was diluted by the addition of 30 ml deionised water and stirred while 1 g sodium ascorbate in 25 ml deionised water was added.

The particles of chitosan rapidly acquired a dark brown colour indicating that the silver ions had been reduced and after 1 hour the suspension was filtered. The solid cbitosan/Ag was washed with deiorused water and dried at 60 C. A solution of 1 g of the dry powder in 100 ml of 0.9% lactic acid (80%) gave an extinction coefficient of 10,600 L mol' cnf' for the chitosan/Ag complex, based on the molar concentration of silver present.

Example 3

g of finely ground chitosan particles was stirred in 70 ml deionised water while 0.6 g AgNO3 inS ml deionised water was added drop wise to it. Stirring continued until the supernatant did not give any precipitate on addition to a solution of NaC1.

The suspension was then diluted to 800 ml with deionised water, and 1 6g ascorbic acid dissolved in 200 ml dcjonised water added. Reduction and solubilisation occurred concurrently to give a strongly coloured (yellow-brown) solution with an extinction coefcient> 10,000 L moF' cm', based on the molar concentration of silver present.

Example 4 p 3

g of fmely ground chitosan particles was stirred in 70 ml deionised water while 0.6 g AgNO3 in 5 ml deionised water was added drop wise to it. Stirring continued until the supernatant did not give any precipitate on addition to a solution of NaCI. The suspension was filtered and the recovered solids dried at 65 C. The dried powder was intimately blended with glycolic acid powder (7 g) and ascorbic acid powder (1 g). 43 g of the powder was weighed out into a beaker, 250 ml deionised water added and the mixture rapidly stirred. Reduction and solubilisation occurred concurrently to give a strongly coloured (yellow-brown) solution with an extinction coefficient> 10,000 L maY' cm', based on the molar concentration of silver present.

Example 5

A 10 g sample of finely ground chitosan particles was stirred in 70 ml deionised water while 0.6 g AgNO3 in 5 ml deionised water was added drop wise to it.

Stirring continued until the supematant did not give any precipitate on addition to a solution of NaC1. The suspension was then filtered and the recovered solids dried at 65 C. The dried powder was intimately blended with ascorbic acid powder (18 g). 7 g of the powder was weighed out into a beaker, 250 ml deionised water added and the mixture rapidly stirred. Reduction and solubilisation occurred concurrently to give a strongly coloured (yellow-brown) solution with an extinction coefficient> 10,000 L moF' crnl, based on the molar concentration of silver present.

Example 6

g of finely ground chitosan particles was stirred in 70 ml deiomsed water and 1.2 g AgNO3 in 10 ml deioaised water added drop wise to it. The chitosan suspension was stined until the filtered off supernatant did not give any precipitate on addition to a solution of NaCi. The suspension was then diluted to 950 ml with deionised water and 9 ml lactic acid (80%) was added to solubilise the chitosanJAg complex. Once a homogeneous solution was obtained a solution of 1.8 g ascorbic acid in 40 ml deionised water was added. A strong yellow-brown colour developed rapidly and full reduction was achieved within 1 hour.

Example 7

S

g of finely ground chitosan particles was stirred in 70 ml deionised water while 0.6 g AgNO3 in 5 ml deionised water was added drop wise to it. Stirring continued until the filtered off supernatant did not give any precipitate on addition to a solution of NaCI. The suspension was diluted by the addition of 30 ml deionised water and stirred while heating to 70-75 C. On reaching the desired temperature 1 ml hydrazine (98%) was added and stirring continued at this temperature for 1 hour then the suspension was filtered, the solid chitosanlAg washed with deionjsed water and dried at 60 C. A solution of 1 g of the dry powder in 100 ml of 0.9% lactic acid (80%) gave an extinction coefficient of 10,200 L mol' cnf' for the chitosan/Ag complex, based on the molar concentration of silver present.

Example 8

A sample (5 g) of chitosanlAg powder prepared as in Example 2 was suspended with stirring in 100 ml of water. Once the particles ofchitosanlAg were thoroughly dispersed, 3 ml lactic acid (80%) was added and the mixture stirred until a viscous solution was formed. This was then transferred to a syringe and the solution extruded into the bottom of a vertical tube containing I litre of a 2% NaOH solution. The stream of polymer solution gelled and gradually rose towards the top of the tube where it was removed and rinsed in several changes of water and then dried to give a brown fibrous product.

Example 9

g of finely powdered chitin having approximately 8% D-glucosarnine residues was slurried in 80 ml de-iomsed water containing 0.3 g AgNO3 until the filtered off supernatant did not give any precipitate on addition to a solution of NaCI. A solution of 0.3 g ascorbic acid in 10 ml deionised water was added and stirring continued for 1 hour, during which time the powder developed a dark brown colour. The solid was filtered off; rinsed well and dried.

Example 10

A solution containing 0.3 g AgNO3 and 8 g sodium alginate in 200 ml deionised water was left to stand for 24 hours in the dark. Then the solution was stirred while 10 ml of a 3.5% solution of ascorbic acid was slowly added. The solution rapidly developed a grey colour, indicating that the silver had been reduced.

Example ii

The solution prepared in Example 10 above was, before reduction of the complexed silver ions, transferred to a syringe and the solution extruded into the bottom of a vertical tube containing I litre of a dilute solution of a soluble calcium salt. The stream of polymer solution gelled on contact with the calcium ions and gradually rose towards the top of the tube where it was removed. The gel was rinsed with several changes of water, immersed in a dilute solution of ascorbic acid or sodium ascorbate, and then rinsed and dried to give a grey fibrous product that from visual inspection had a uniform colour.

Example 12

The solution prepared in Example 10 above was, before reduction of the complexed silver ions, transferred to a syringe and the solution extruded into the bottom of a vertical tube containing 1 litre of a dilute solution of a soluble calcium salt and ascorbic acid or sodium ascorbate. The stream of polymer solution gelled and gradually rose towards the top of the tube where it was removed and rinsed with several changes of water and then dried to give a grey fibrous product that from visual inspection had a uniform colour. Thus, the reduction step may be combined with the coagulation/gelation step.

Example 13

A homogeneous solution of the chitosan/Ag1 complex, prepared as described in Example 1, was heated to 70-75 C and 1.0 ml hydrazine (98%) in 5 ml deionised water added, followed by a further 1.5 ml lactic acid (80%) to redissolve the precipitated chitosan-silver complex. There was a rapid development of an intense yellow-brown colour, which on cooling back to room temperature showed an extinction coefficient similar to that of the pmduct obtained in Example 1.

Example 14

To a solution of the chitosan/Ag4 complex, as prepared in Example 1, was added 5 g of a non-ionic surfactant (Tween 20) followed by 0.9 g ascorbic acid in 20 ml deionised water. The stirred solution rapidly changed from colourless to a strong reddish-brown colour, indicating that reduction had taken place. The shelf life of this solution was found to be greater than that of a solution prepared similarly but with omission of the surfactant.

Example 15

A solution containing 10 g poly(vinylamine) in 500 ml deionised water was stirred while 0.6 g AgNO3 in 10 ml deionised water was added. After standing overnight the solution was stirred while a solution of 0.9 g ascorbic acid in 20 ml deiomsed water was added. An intense yellow- brown colour rapidly developed and reduction was complete within 1 hour.

Example 16

g of finely ground chitosan particles in 100 ml deionised water was stirred while heated to 80-85 C. Once this temperature was reached 0. 6 g AgNO3 in S ml deionised water was added drop wise to the suspension and stirring continued at 80-85 C for 1-2 hours. The mixture was diluted to 980 ml with cold deionised water and 9 ml lactic acid (80%) added to solubilise the chitosan/Ag complex.

Once a homogeneous solution was obtained, 0.9 g ascorbic acid in 10 ml deionised water was added and stirring continued for 1 hour, by which time the solution had developed a strong reddish-brown colour. The solution gave an extinction coefficient at 400 nm, based on the molar concentration of silver present, of> 10,000 L mol' cm'.

Examule 17 g of finely ground chitosan particles in 100 ml deionised water was stirred while heated to 80-85 C. Once this temperature was reached 0.6 g AgNO3 in 5 ml deionised water was added drop wise to the suspension and stirring continued at 80-85 C for 1-2 hours. The suspension was then filtered and the recovered solids dried. The dried powder was intimately blended with 7 g of glycolic acid powder and ascorbic acid powder. 4.5 g of the mixed powder was weighed out into a beaker and 250 ml deiomsed water was added and the mixture stirred.

Solubiisation and reduction occurred concurrently to give a strongly coloured solution with an extinction coefficient at 400 nm, based on the molar concentration of silver present, of> 10,000 L moV' cm'.

Example 18

A solution of chitosan/Ag , prepared as described in Example I above, was spray dried by a conventional process and isolated as a fine, free-flowing brown powder that could be rapidly redissolved by addition of water to give a solution having similar X, and extinction coefficient values to those of the original solution.

Example 19

g of sodium carboxymethyl cellulose (DS 0.9) was slurried in 200 ml isopropyl alcohol containing 10% water while 0.3 g AgNO3 in 2.5 ml of deionised water was added drop wise. After stirring for 2 hours 0.5 g sodium ascorbate, dissolved in the minimum amount of water, was slowly run into the suspension.

Stirring was continued for a further hour then the grey powder was filtered off, dispersed in 500 ml water, and the mixture stirred until a homogeneous solution was obtained. *1 18

Example 20

A suspension of 10 g of finely ground chitosan particles was stirred in 70 ml delonised water while 0.6 g AgNO3 in 5 ml deionised water was added drop wise to it. Stirring was continued until the supernatant did not give any precipitate on addition to a solution of NaC1. The suspension was diluted to 470 ml with deionised water and 9 in! lactic acid (80%) was added to solubilise the chitosan/Ag' complex. Once the complex was dissolved 2.5 g solid cetyltrimethylammonium bromide was added to the well-stirred solution, followed by 0.62 g ascorbic acid in 20 ml deicrnised water. No change in the colour of the solution was observed and there was no evidence of the development of the intense brown colour characteristic of the chitosan/Ag complex. The product was isolated as a pale yellow-brown solid on raising the pH of the solution to> 10 by addition of NaOH, filtering and rinsing well with water and drying. Redissolving the recovered solid in 0.1 M lactic acid gave a clear colourless solution that had an extinction coefficient < 100 L mol' cm, based on the molar concentration of silver present. Clear, colourless transparent films could be cast from the solution, which remained stable on standing for 3 months in daylight. a

Claims

CLAIMS

1. A process for producing a polymer..metal complex comprising the steps of: (i) contacting a solution comprising one or more metal salts with a polymer which is capabie of interacting with the metal salt to form a polymer-metal ion complex and wherein the polymer and the polymer metal ion complex are in the solid phase, said solid phase comprising the polymer in an amount of at least 25 % by weight and/or being in the form of a power or flake; (ii) optionally dissolving the polymer-metal ion complex; and (iii) chemically reducing metal ions in the polymer-metal ion complex to form the polymer-metal complex.

2. A process according to Claim 1, wherein the polymer comprises functional groups selected from amine, carboxylic acid, carboxylate, hydroxyl, and mixtures thereof.

3. A process according to Claim 1 or Claim 2, wherein the polymer is selected from the group consisting of chitin and chitosan.

4. A process according to Claim 1 or Claim 2, wherein the polymer is selected from the group consisting of alginate, polyvinylainine, carboxymethyl cellulose and hyaluronic acid.

5. A process according to any one of Claims I to 4, wherein (i) is carned out at a temperature of 50 to 95 C.

6. A process according to any one of Claims Ito 5, wherein (i) and (ii) are independently carried out either at a temperature of 50 to 95 C or at room temperature.

7. A process according to any one of Claims I to 6, wherein the one or more metal salts are present in an aqueous solution.

8. A process according to any one of Claims I to 7, wherein the one or more metal salts are selected from salts of silver, copper, gold, palladium, platinum, tin, and mixtures thereof.

9. A process according to any one of Claims I to 8, wherein the polymer-metal ion complex is dissolved at a pFI below 6.5.

10. A process according to any one of Claims 1 to 9, wherein (iii) is carried out using a reductone.

Ii. A process according to Claim 10, wherein the reductone is ascorbic acid or a salt thereof.

12. A process according to any one of Claims I to 11, wherein prior to (iii) the polymer metal ion complex is contacted with a quatemary ammonium compound.

13. Product obtainable by the process of any one of Claims 1 to 12.

14, Polymer-metal complex in solution, which is translucent and free of suspended particulate metal-containing species.

15. A solid premix comprising a polymer-metal ion complex and a solid reducing agent.

16. A solid premix according to Claim 15, wherein the reducing agent is acidic.

17. A solid premix according to Claim 15 or Claim 16, wherein the premix further comprises an acid.

18. A process for the production of a polymer-metal complex comprising the steps of: (a) contacting an aqueous solution comprising one or more metal salts with a solution comprising alginic acid or a salt thereof, polyvinylamine or a mixture thereof; (b) treating the solution in (a) with a gelling agent to form a gel; and (c) chemically reducing metal ions in the gel to metal atoms, wherein (b) and (c) may be carried out simultaneously or sequentially in any order.

19. A process according to Claim 18, wherein the gelling agent is a water soluble salt of calcium.

20. A process according to Claim 18 or Claim 19, wherein (b) and (c) are carried out simultaneously.

21. A process according to any one of Claims 18 to 20, wherein the one or more metal salts are selected from salts of silver, copper, gold, palladium, platinum, tin, and mixtures thereof.

22. A process according to any one of Claims 18 to 21, wherein (c) is carried out using a reductone.

23. A process according to Claim 22, wherein the reductone is ascorbic acid or a salt thereof 24. The use of a reductone for reducing a polymer-metal ion complex to a polymer-metal complex.