Silver-containing foam structure

[0001] The present invention relates to the antibacterial and hydrophilic polyurethane foam structure. More specifically, the antibacterial and hydrophilic foam structure contains an increased amount of silver both in the polymer matrix and inside the foam cells. Furthermore, the invention provides a method for producing such an antibacterial hydrophilic foam structure.

Technical background [0002] WO-A1-97 / 42985 discloses a wound dressing comprising a layer of absorbent foam material that includes a hole pattern. The holes are open on the side of the foam material that lies adjacent to the patient's skin when the dressing is worn, and the layer of foam material is coated with a layer of hydrophobic gel sticking to the skin, with those end portions of the wall holes in the foam material being adjacent the patient's skin is coated with a gel when the dressing is worn. There is no disclosure of any particular antibiotic compound in the dressing. [0003] US A 5,662,913 describes the use of silver salts stabilized by forming complexes with acyclic polyether polymers. In addition, silver salt anions are in excess of silver ions. The stabilized silver salt complexes of US 5,662,913 can be incorporated into foam structures. The object of the invention disclosed in this patent is to provide photostable, non-staining antimicrobial metal compositions for protection against infection, and to give polyurethane-based foam products antimicrobial properties. Nothing is disclosed regarding the regulation of silver release from the polyurethane structure.

[0004] WO 2004/007595 discloses a product of flexible cellular polyurethane foam that can be made in the presence of a controlled silver release silver component. The release of silver from the structure is usually slow, which is an advantage in some applications.

[0005] EP-A1-1 486 523 and US 4937273 relate to polyurethane foams containing antimicrobial silver bound to zeolite particles. The release of silver from the structure is usually slow, which is an advantage in some applications.

[0006] Different wounds require different release profiles of antimicrobials such as silver. For infected iran wounds that are easily infected, however, it would be desirable to use a dressing that would initially be able to release large amounts of antimicrobial silver and that would be able to maintain such release for a long time.

Summary of the invention [0007] The present invention provides a method of producing an antibacterial and hydrophilic polyurethane foam structure that can be used as a wound dressing. The method comprises steps

a) providing an aqueous phase containing a surfactant;

b. providing a polyether terminated with isocyanate groups having a functionality exceeding 2;

c) mixing this aqueous phase and this polyether terminated with isocyanate groups, immediately transferring the resulting mixture to formyl or a continuous web, thereby forming a foam structure; and

d) drying this foam structure to obtain a moisture content of at most 10% (w / w), preferably at most 8% (w / w), and even more preferably at most 5% (wt).

[0008] A basic feature of the method is that the aqueous phase in step a) also contains a silver salt.

EP 1 964 580 B1

Part of this silver salt is dissolved in this aqueous phase, and the rest of this silver salt is dispersed in this aqueous phase. The advantage of this method is that silver ions with antibacterial activity are released in a beneficial manner over an extended period.

The above-mentioned silver salt is selected from the group consisting of silver sulfate, silver citrate, silver acetate, silver carbonate, silver lactate and silver phosphate or a mixture of these salts.

[0009] Furthermore, it is preferred to coat this mold or continuous web with casting paper before adding the mixture in step c). This casting paper is removed before the drying step d).

[0010] It is further preferred to apply the cross-linked silicone gel to one surface of the foam structure obtained after step d), after which the gel is cured in the presence of a catalyst. The catalyst is preferably a platinum complex.

[0011] Finally, the present invention provides an antibacterial and hydrophilic polyurethane foam structure with a pore size in the range of 30 to 1000 Pm, which structure can be produced by the above disclosed ₂ way. Preferably, the amount of accumulated silver released per cm² foam structure after 48 hours

2 2 is over 0.2 mg / cm², more preferably more than 0.25 mg / cm², and most preferably more than 0.30 mg / cm². Also,₂ amount of accumulated silver released in cm² the foam structure after 72 hours is preferably over 0.2 mg / cm2², more preferably more than 0.35 mg / cm²and most preferably more than 0.40 mg / cm². Preferably, the amount on₂ The collected silver is at most 0.80 mg / cm² after 48 hours, more preferably after 96 hours, and most preferably after 120 hours.

[0012] Preferably, the antibacterial characteristics of the foam structure are such that a round sample of this foam with a diameter of 20 m and a thickness of 5 mm, exposed to 10 ml of bacterial fluid simulating wound fluid (1: 1 solution of fetal calf serum with water peptone (aqueous solution containing 0.9% (w / w) NaCl 0.5% (w / w peptone)) at 35 ° C ± 2 ° According to the reference method zASTM E 2149, is able to reduce the number of viable cells of Pseudomonas aeruginosa from 10⁶ to less than 10² within 72 hours to reduce the number of live Staphylococcus aureus cells from 10⁶ to less than 10² within 120 hours.

[0013] The present invention also provides a wound dressing comprising such an umbilical structure.

Detailed description of the invention [0014] Accordingly, the present invention provides a method of producing an antibacterial and hydrophilic foam structure with increased release of silver ions with antibacterial effect over time. [0015] The hydrophilic foam structure of the present invention is based on hydrophilic polyurethane foam. Useful hydrophilic polyurethane foams include those known as Hypol (trade name) foams. Hypol foams can be made from the hydrophilic Hypol prepolymers sold by Dow Chemicals.

[0016] Susceptible hydrophilic polyurethane foams can be made by mixing a polyether terminated with isocyanate groups having functionality above two with a surfactant and water and pouring the mixture onto the surface.

[0017] Preferred isocyanate terminated polyethers include Hypol FHP 2000, 2001, 3000, 3001, 2002 and 2000HD, sold by Dow Chemicals. Hypol described in a brochure published by WR Grace and Co. "Hypol: foamable hydrophilic polymers-laboratory proceduresandfoam formulations". Their production and use are disclosed in British Patent Nos. 142971 1 and 1507232.

[0018] Suitable surfactants for making susceptible hydrophilic polymer foams include nonionic surfactants. For beneficial non-ionic agents

Surfactants include oxypropylene oxyethylene block copolymers known as Pluronic (trade name) sold by BASF Wyandotte. Preferred Pluronic surfactants include L65, F87, P38, P75 and L62.

[0019] Suitable silver sources are silver salts with moderate water solubility. It is also important that silver salts are stable under sterilization conditions and that they are pharmaceutically acceptable. In one embodiment of the invention, the silver salts with moderate water solubility are mixed with the silver salts with low water solubility. It is crucial that the silver salt is dispersed in the aqueous reaction mixture during the manufacturing process. Examples of silver salts that can be used in accordance with the present invention belong to the group consisting of silver sulfate, silver citrate, silver acetate, silver carbonate, silver lactate and silver phosphate or mixtures of such salts.

[0020] To produce a typical foam, 100 parts by weight of Hypol FHP 2000, 2001, 3000, 3001, 2002 or 2000HD are mixed with 0.3 to 7 parts by weight of surfactant or mixtures of surfactants, 2 to 9 parts by weight of silver salt, such as silver sulfate, and 30 to 300 parts by weight of water and the foaming mixture is poured onto the surface. Typical foaming mixtures have a cream time of 20-30 seconds, a growth time of 60-250 seconds and a curing time of 400-800 seconds.

In addition, the appropriate foam pore size can vary from 30 to 1000 μm.

[0021] The silver-containing hydrophilic polyurethane foam may be derived from residues derived from a mono-alkyl or mono-alkylaryl polyalkylene glycol ether. Such foams can be made by reacting with water a polyisocyanate reaction product with functionality above 2i monoalkyl or alkylaryl polyalkylene glycol ether.

[0022] Preferred polyalkylene glycol mono-alkyl aryl ethers are those in which the alkylene group contains up to 4 carbon atoms. A more preferred alkylene group is an ethylene group.

[0023] Suitable polyalkylene glycol mono-alkyl ethers for producing the reaction product are those in which the alkyl group contains 1 to 20 carbon atoms. Preferred alkylene ethers are those in which the alkyl group is a methyl group. Another class of preferred polyalkylene glycol mono-alkyl ethers are those in which the alkyl group contains 10 to 18 carbon atoms, e.g., lauryl or cetyl.

[0024] Suitable polyalkylene glycol mono-alkyl aryl ethers are those in which the aryl group is phenyl. Preferred ethers are those in which the alkyl group contains 1 to 20 carbon atoms, e.g. octyl or nonyl.

[0025] The average molecular weight of the polyalkylene glycol mono-alkyl or alkylaryl ether may conveniently be 180 to 6000. Useful ethers for producing reaction products to obtain flexible foams of the invention have an average molecular weight of 180 to 1300, and preferably have an average molecular weight of from 350 to 1300 1000.

[0026] Suitable ethers for producing reaction products to obtain the rigid foams of the invention have an average molecular weight of 1500 to 6000, and preferably have an average weight of 3000 to 5000. [0027] Suitable ethers are polyethylene glycol monolauryl ethers with an average molecular weight of about 1,090 and 360, known as Brij 35i Brij 30, respectively, available from Honeywell Atlas, and polyethylene glycol monomethyl ethers with an average molecular weight of about 500i 5000, known as PEG monomethyl ether with a molecular weight of 550 and 5000, respectively, available from Aldrich Chemicals.

[0028] Suitable polyethylene glycol monononyl phenyl ethers are commercially available under the trade names Antarox CO-320 and Antarox CO-990. Useful polyethylene glycol monononyl phenyl ethers

An average molecular weight of about 440 is known as Antarox CO-520 and CO-990, respectively, are available from GAF (Great Britain) Co. Limited.

[0029] The polyethylene glycol mono-alkyl or alkylaryl ether used according to the invention will usually contain water. Preferably, however, the ether contains less than 1% by weight of water to limit the number of urea groups formed by reaction with the polyisocyanate.

[0030] The polyisocyanate used to prepare the reaction product will have a functionality of over 2, for example 2 to 5, and preferably its functionality will be 2.2 to 3.5. Suitable polyisocyanates include aliphatic and aromatic polyisocyanates. Preferred polyisocyanates are aliphatic polyisocyanates. Aliphatic polyisocyanates are usually liquid at ambient (room) temperature and are therefore convenient for use in a liquid reaction mixture. A useful aliphatic polyisocyanate for use according to the invention is a buret of 1,6-hexamethylenediisocyanate with a functionality of 2.6, known as Desmodur N100 (trade name), available from Bayer AG

[0031] Preferred aromatic polyisocyanates for producing the reaction product are polymeric methylene diisocyanates. Polymeric methylene diisocyanates include a mixture of 4,4'-diphenylmethane diisocyanates and one or more polymeric homologues. Useful polymeric methylene diisocyanates are known as SUPRASEC VM 20, (trade name) VM 50, DNDi VM 90, available from ICI, with functionalities of 2.13, 2.49, 2.70 and 2.90 respectively.

[0032] A reaction product suitable for use as a dressing according to the invention may be the reaction product of one or more polyisocyanates and one or more mono-alkyl or arylalkyl polyalkylene glycol ethers, including mixed alkyl and alkylaryl ethers. The reaction product may conveniently be prepared using a chain extender.

[0033] Suitable chain extenders for use in preparing the reaction product include ethanediol, 1,3-propanediol and 1,4-butanediol.

[0034] As already mentioned, the antibacterial and hydrophilic polyurethane foam structure of the present invention can be coated on one side with cross-linked silicone gels. The crosslinked silicones that are used to coat the antibacterial and hydrophilic polyurethane foam structure of the present invention can be conveniently characterized by their tensile strength, penetration capability and peel strength. As used herein, the term "tensile strength" means the maximum tensile load that can be applied (using an Instron standard instrument) to a strap of appropriate cross-linked silicone with a width of 5 cm and a thickness of 3 mm.

[0035] Cross-linked silicones can be made in known manner from linear silicones containing reactive groups. Preferably, the gels are prepared by reacting a vinyl substituted silicone and a hydride containing silicone in the presence of a suitable catalyst, such as a platinum catalyst. [0036] The starting silicones may have a viscosity in the range of 100 - 10,000 mPas, a number average molecular weight in the range of 350 to 40,000, and may for example contain 0.004 to 0.4 mmol of reactive groups / g.

[0037] When silicones are prepared by cross-linking a mixture of two or more silicones, the molecular weights of the various components and / or their degree of substitution with reactive groups may be different. This makes it possible to produce gels with different physical properties simply by changing the proportions of the ingredients.

[0038] Ingredients for making suitable crosslinked silicones for use in antimicrobial 4

The hydrophilic polyurethane foam structure of the present invention is available from Wacker, under the name Wacker silgel 612. This gel is a poly (dimethylsiloxane) substituted with vinyl groups and containing hydride groups.

[0039] As already mentioned, the structures of the present invention are produced by coating a sheet of foamed material with a non-crosslinked silicone material and then causing it to crosslink. For gels resulting from the reaction of vinyl groups of one component with the hydride groups of another component, such curing will typically be carried out in the presence of a catalyst, such as a platinum complex at a concentration of 5 to 15 ppm. In this case, the gel may cure at room temperature for several days, but preferably an elevated temperature is used. For example, silicone gels may be cured at a temperature of 40 ° to 120 ° C, and preferably at a temperature between 80 ° and 100 ° C. At 80 ° C, the curing time will usually be from 10 seconds to 10 minutes, for example from 1 to 5 minutes. At 50 ° C, the curing time will usually be from 10 minutes to 2 hours, for example from 15 minutes to 1 hour.

[0040] Examples of suitable chemically cross-linked silicone gels (polydimethylsiloxane gels) include platinum-cured 2-component addition curing RTV silicone. Examples of gels that can be used include SilGe1612 from Wacker-Chemie GmbH, Burghausen, Germany, and MED-6340 from NuSil Technology, Carpinteria, USA.

[0041] Thus, the present invention provides a dressing characterized by an absorbent layer, an antibacterial and hydrophilic polyurethane foam material containing silver ions which contains a pattern of holes that are open on the side of the foam material adjacent to the skin of the patient during use. Preferably, the foam material is covered with a layer of hydrophobic cross-linked silicone gel that adheres to the skin and in which the walls of the holes in the foam material are covered with gel in those end portions of those walls that lie adjacent to the patient's skin when the dressing is used.

[0042] In a first preferred embodiment for wounds from which fluid is only slightly or in normal amounts, the foam structure comprises a pore pattern in the form of pores in the antimicrobial foam material. If the cross-linked silicone gel is applied, this gel also slightly penetrates into the open pores of the foam material at the boundary of the gel layer, without closing the pores completely.

[0043] Preferably, the foam material is coated with a layer of liquid impermeable material on that side of the foam material that is distant from the skin of the patient during use.

[0044] The dressing comprising an antibacterial foam structure coated with a cross-linked silicone gel has an adhesion strength F1 of 0.1-2.0N, suitably 0.2-1.3N, and preferably 0.2-0.7N.

[0045] In a first embodiment, the layer thickness of the gel mixture is 0.05-1.0mm.

[0046] The invention will now be described in more detail with reference to the attached drawings, of which:

Figure 1 is a schematic perspective view of a piece of dressing according to the invention in one embodiment;

Figure 1A is an enlarged view of the feature of Figure 1;

Figure 2 schematically illustrates the device for applying the cross-linked silicone gel on the antibacterial structure of the present invention;

Figure 3 schematically shows how the release of silver from the structure contains 5 is measured

Silver;

Figure 4 shows silver release charts comparing the material presented here (Sample A) with two commercially available silver containing foams (Sample B described in WO2002062403 and Sample C described in US5681575 (A) and US5837275 (A)). Figure 4A shows the amount of silver released at specific time points, and Figure 4B shows the cumulative silver release. Figure 5 is graphs of the prolonged antimicrobial activity of the present invention (Sample A) compared to two other silver containing foam products (Sample B described in WO2002062403 and Sample C described in US5681575 (A) and US5837275 (A)). Figure 5A shows the effect on Staphylococcus aureus and Figure 5B shows the effect on Pseudomonas aeruginosa. For both types of bacteria, the sample of the present invention shows higher antimicrobial efficacy; and [0047] Scheme 1 illustrates the preparation of a dressing comprising the structure of the present invention.

Scheme 1: Preparation of a foam containing silver. The aqueous phase contains water, a silver salt such as silver sulfate and a surfactant

Schematic description of the foaming process

<img file="PL1964580T3_D0001.tif" />

[0048] Scheme 1 shows a production method. The polyurethane prepolymers are mixed with the aqueous phase 6

EP 1 964 580 B1 containing surfactants, dispersed and dissolved silver salt in a dispensing and mixing device. The reaction mixture is then transferred to a mold or continuous web, lined with cast paper. After the polymerization reaction, the casting paper is removed from the castings and the resulting foam is dried to a moisture content of at most 10% (w / w), preferably at most 8% (w / w), most preferably at most 5% (w / w). The foam is then wound on plastic cores with paper between the layers and packaged.

[0049] Figure 1 illustrates a piece of dressing according to one embodiment of the invention. The dressing consists of an absorbent foam material 2 that has been coated with a gel layer 3 on the side that will lie adjacent to the wound or skin of the patient when the dressing is used. As illustrated schematically in Figure 1A, the gel layer 3 is arranged so that even a portion of the walls or open cells or pores 4 in the foam material that are open from its gel-coated side is gel-coated. Due to the fact that the gel layer3 does not close, but only covers a part of the walls in the final part of the pores of the foam material that comes into contact with the wound, excess fluid from the wound can seep into the foam material2 and be absorbed by it. The gel layer also forms a release layer that prevents the foam material from coming into direct contact with the patient's wound or skin. The total thickness of the gel layer, i.e. taking into account the penetration into the pores of the foam material, is 0.1-2.0 mm. Part of the pores in the foam material that comes into contact with the wound is closed by a layer of gel.

In order for the invention to provide a dressing having a dry outer surface, the dressing comprises a liquid-impermeable layer 5 on the side opposite to the gel layer 3. This impermeable layer 5 may be a thin liquid-impermeable but vapor-permeable plastic film, for example polyurethane film.

[0051] The dressing illustrated in Figure 1 is intended for use on wounds that secrete fluid in a range from low to normal. The foam layer has a thickness of 1-10 mm, preferably 2-6 mm. As mentioned previously, the foam material acts both as an absorbent and as a gel carrier, so that the dressing as a whole will be very soft and elastic. Due to the fact that the gel sticks to the skin surrounding the wound, the dressing will be held in place so that the gel provides a sealing effect and prevents maceration, i.e. it prevents fluid from flowing from the wound over healthy skin and softening its horny layer. The open structure of the gel layer and foam material also allows skin to breathe. The gel adhesive used according to the invention is completely different in nature from the adhesives usually used for fixing dressings, for example from acrylate adhesives or hot melt adhesives which are currently used for this purpose. The significant difference between these adhesives and the adhesive used according to the invention is that the gel is much softer and has a better "wetting capacity" than these adhesives. As a result, gels can have a much lower specific tack, i.e. less adhesion per unit of contact surface area, than the specific tack, which harder adhesives need to exhibit to achieve the same effective total adhesion that is provided by the gel.

[0052] Figure 2 schematically illustrates a device for use in applying a crosslinked silicone gel layer to a structure according to the present invention. The illustrated device includes a conveyor (not shown) by which the plastic film 8 is transferred from left to right in Figure 2. Layer 9 of the uncured gel mixture is placed on the film 8. Gel mixture means a mixture of components that form a gel after curing, including polymers that can react with each other to form a crosslinked structure. Layer 10 of absorbent foam material is applied to layer 9 of the uncured gel mixture using a roller 11 and layer 9, 10 is transported subsequently

Not to the oven 12. The gel mixture cures when passing through the oven 12 or, alternatively, between hot plates and forms a gel layer on the underside of the foam material.

[0053] It was found that with proper selection of the gel mixture, pressure force F, amount of gel mixture, time between application of the foam material and heating of the layers, curing temperature etc., a discontinuous gel coating will form on the foam material. This is because the mixture is sucked by capillary action into those pores or holes in the foam material that are open on the side of the foam material to which the gel mixture adheres. When applying a gel coating to foam material that does not contain openings other than pores, the gel mixture must be applied in a layer of such thickness to ensure that the excessive number of pores open from the underside of the foam material is not clogged or blocked by the gel coating. The viscosity of the gel mixture and the size of the pores in the foam material also affect the tendency of the mixture to penetrate into the pores. It has been found that the thickness of the applied gel mixture layer should preferably be 0.051.0 mm. Most of the gel mixture layer is sucked into the foam, so that the entire gel layer, including air and foam, will have a thickness of 0.1-2.0 mm.

[0054] In the first application of the above method, a small cell sheet, soft, hy, was used to coat the underside of the antibacterial polyurethane foam sheet with silicone gel₃ Drum polyurethane foam with a density of 80 - 150 kg / m³ and 5 mm thick.

[0055] The silicone mixture was made of SilGel 612 obtained from Wacker, with a mixing ratio of component A and component B of 1.0: 0.9. The viscosity of the uncured mixture was about 1000 mPa.

[0056] The polyurethane sheet was placed on a 0.2 mm thick silicone mixture without applying pressure F to the roller 11, in other words the silicone mixture was only exposed to the weight of the foam sheet. The transport time for the foam material 10 and the underlying silicone mixture 9 from the roller 11 to the oven 12 was one minute and the curing temperature was 130 ° C. The residence time of the oven cured silicone was minutes. The polyurethane film with high vapor permeability and a thickness of 0.025 mm was then firmly glued to the foam on its opposite side to the gel coating. With this ratio in the mixture, the penetration value of the silicone gel was 16 mm, and the measured force of adhesion of the dressing to the skin was 0.42 N. It has been found that under these conditions the gel mixture layer should preferably have a thickness of at least 0.1 mm so as to obtain a suitable discontinuous gel coating on the foam material.

[0057] When the thickness of the gel mixture layer is greater than 0.4 mm, an excessively large percentage of pores in the foam material will be blocked, which will result in insufficient permeability of the gel coating.

[0058] From the above, it is clear that if the method described with reference to Figure 2 is carried out, the quality of the final product will depend on many factors. Therefore, no general limits can be given for these factors and such limits must be empirically determined for the gel mixture and foam material used.

[0059] In this connection, the described method makes it very easy to manufacture a dressing of the type described with reference to Figure 1. The method is also very flexible and allows the production of dressings with differing absorbency in essentially the same way and using the same device. [0060] The dressing described can of course be sterilized, e.g. by sterilization with ethylene oxide or steam sterilization and is intended for delivery in various sizes and for different types of wounds, both in sterile packaging and in non-sterile packaging. Because of their softness they are useful

EP 1 964 580 B1 for use in combination with compression bandages and can be used successfully on blisters, leg ulcers and similar wounds. The high degree of flexibility makes them useful for use on aching joints, such as knee pain and elbow pain, even in the later stages of healing sore areas. Dressings can also be cut to the size of the corresponding sore or wound.

[0061] It is understood that the exemplary embodiments described can be modified within the scope of the invention, especially with respect to the materials described.

[0062] The invention will now be further described in the attached examples.

Example 1: Preparation of the foam structure [0063] The aqueous phase for the foam making process was prepared by dissolving / dispersing the Puronic F87 nonionic surfactant, silver sulfate and activated carbon. The final concentrations of these components in the aqueous phase were 0.5% (w / w) Pluronic F87 and 2.2% (w / w) silver sulfate. The dissolved silver sulfate concentration was 0.8% (w / w) and the rest of the silver sulfate was dispersed in the aqueous phase.

[0064] At the same time, a mold lined with casting paper was prepared. The mold was of sufficient depth to obtain a 5 mm thick sheet of foam.

[0065] The Hypol 2001 prepolymer (isocyanate-terminated polyether) was added to the aqueous phase in a dispersion and mixing device in an amount of 40% (w / w) at room temperature. The resulting mixture was immediately transferred to a casting mold. The foaming lasted 30 s, after which the foam was cured for 10 minutes. After curing, the casting papers were removed and the foam was dried to a moisture content of at most 10% (w / w) at 120 ° C. (See Figure 1 and Figure 2.)

Example 2: Absorption of foam material [0066] Samples of the foam product obtained in Example 1, Sample A and two commercially available products, Sample B described in WO2002062403 and Sample C described in US5681575 (A) and US5837275 (A), cut into test pieces 6 x 6 cm and weighed. Then, the test pieces were soaked in excess tap water. After three hours, the fittings were weighed again. The results obtained are shown in Table 1: Table 1

<td></td><td>Dry weight (g)</td><td>Wet weight (g)</td><td>Absorption (g / 36 cm²)</td><td>Absorption (G / cm²)</td>

<td>Sample A</td><td> 2,82</td><td> 35,5</td><td> 32,7</td><td> 0,91</td>

<td>Sample B</td><td> 3,52</td><td> 28,5</td><td> 25,0</td><td> 0,69</td>

<td>Sample C</td><td> 3,31</td><td> 33,0</td><td> 29,7</td><td> 0,82</td>

[0067] The results indicate that the product of Example 1 (Sample A) has good absorption properties.

Example 3: Silver release [0068] Circle-shaped samples with a diameter of 20 mm were punched out of the material obtained according to Example 1, here referred to as Sample Ai of two commercially available products, Sample B described in WO2002062403 and Sample C described in US5681575 (A) and US5837275 (A). Figure 3 shows some details of the device for measuring the release of silver, specifically the 6-well Falcon ™ Multiwell unit (2) and the corresponding cell (4) for cell culture, both from Becton Dickinson Labware (Diffu9 membrane

In culture cells (4) for cell culture, the cells were removed and replaced with a waterproof polyamide film. The hole (6) with a diameter of 12 mm was punched out of the bottom foil. The dry sample (10) was placed in the cell culture insert (4) at the hole (6). A weight (12) made of stainless steel, weighing 15 g and a diameter of 20 mm was placed on top of the sample (10) to compress and attach the sample to the bottom foil.

[0069] A specified amount of 0.15 M aqueous NaNO3 solution (henceforth referred to as the test solution (8)) was added to the Multiwell ™ unit (2) according to the following scheme (table 2):

Table 2

<td>0 h</td><td>6 h</td><td>24 h</td><td>48 h</td><td>72 h</td><td>96 h</td><td>120 h</td><td>144 h</td><td>168 h</td>

<td>3.5 ml</td><td>1.5 ml</td><td>1.5 ml</td><td>1.5 ml</td><td>1.5 ml</td><td>1.5 ml</td><td>1.5 ml</td><td>1.5 ml</td><td>0 ml</td>

[0070] The cell culture insert (4) was placed in the Multiwell ™ unit (2), thus allowing contact between the test solution (8) and the sample (10). The cover of the two-compartment model was put on. At each moment of sampling, the test solution absorbed by the sample was collected (10). After each sampling, a new, fresh test solution was added to the clean Multiwell ™ unit in which the cell culture insert (4), still containing the same sample (10), was placed. All 5 samples were tested three times throughout the entire test. At each sampling the amount of silver released was determined by means of a silver ion electrode.

<td>A sample</td><td>0 h₂mgAg / cm²</td><td>0 h accumulated₂mgAg / cm²</td><td>6 h₂mgAg / cm²</td><td>6 h accumulated₂mgAg / cm²</td>

<td>AND</td><td> 0</td><td> 0</td><td> 0,006</td><td> 0,006</td>

<td>B</td><td> 0</td><td> 0</td><td> 0,005</td><td> 0,005</td>

<td>C</td><td> 0</td><td> 0</td><td> 0,002</td><td> 0,002</td>

<td colspan="2">A sample</td><td colspan="2">24 h₂mgAg / cm²</td><td colspan="2">24 h accumulated₂mgAg / cm²</td><td colspan="2">48 h₂mgAg / cm²</td><td colspan="3">48 h accumulated₂mgAg / cm²</td><td colspan="2">72 h₂mgAg / cm²</td><td colspan="2">72 h accumulated₂mgAg / cm²</td>

<td colspan="2">AND</td><td colspan="2"> 0,134</td><td colspan="2"> 0,14</td><td colspan="2"> 0,18</td><td colspan="3"> 0,32</td><td colspan="2"> 0,15</td><td colspan="2"> 0,47</td>

<td colspan="2">B</td><td colspan="2"> 0,010</td><td colspan="2"> 0,015</td><td colspan="2"> 0,002</td><td colspan="3"> 0,017</td><td colspan="2"> 0,010</td><td colspan="2"> 0,027</td>

<td colspan="2">C</td><td colspan="2"> 0,005</td><td colspan="2"> 0,007</td><td colspan="2"> 0,010</td><td colspan="3"> 0,017</td><td colspan="2"> 0,020</td><td colspan="2"> 0,037</td>

<td>A sample</td><td colspan="2">96 h mg Ag / cm²</td><td colspan="2">96 h accumulated₂mgAg / cm²</td><td colspan="2">120 h mg Ag / cm²</td><td colspan="2">120 h accumulated₂mgAg / cm²</td><td>144 h mg Ag / cm²</td><td colspan="2">Accumulated 144 h₂mgAg / cm²</td><td colspan="2">168 h mg Ag / cm²</td><td>168 h accumulated₂mgAg / cm²</td>

<td>AND</td><td colspan="2"> 0,13</td><td colspan="2"> 0,06</td><td colspan="2"> 0,09</td><td colspan="2"> 0,69</td><td> 0,07</td><td colspan="2"> 0,76</td><td colspan="2"> 0,07</td><td> 0,83</td>

<td>B</td><td colspan="2"> 0,010</td><td colspan="2"> 0,037</td><td colspan="2"> 0,014</td><td colspan="2"> 0,051</td><td> 0,010</td><td colspan="2"> 0,061</td><td colspan="2"> 0,010</td><td> 0,071</td>

EP 1 964 580 B1

<td>A sample</td><td>96 h mg Ag / cm²</td><td>96 h accumulated₂mgAg / cm²</td><td>120 h mg Ag / cm²</td><td>120 h accumulated₂mgAg / cm²</td><td>144 h mg Ag / cm²</td><td>Accumulated 144 h₂mgAg / cm²</td><td>168 h mg Ag / cm²</td><td>168 h accumulated₂mgAg / cm²</td>

<td>C</td><td> 0,014</td><td> 0,051</td><td> 0,014</td><td> 0,065</td><td> 0,010</td><td> 0,075</td><td> 0,08</td><td> 0,083</td>

[0071] The results obtained are shown in Figures 4A and 4B. The product of Example 1 releases about 70% of the silver content over a period of one week. The highest release rate is achieved after about 48 hours.

Example 4 Antimicrobial effect [0072] Antimicrobial effect was measured by the method based on the reference method ASTM E 2149.

Samples (20 mm in diameter) of the silver containing foam from Example 1 (Sample A) and reference material (Sample B described in WO2002062403, Sample C described in US5681 575 (A) and US5837275 (A) and the control sample, foam described in Example 1, but not containing silver) were placed in flasks with bacteria (Staphylococcus aureus or Pseudomonas aeruginosa) and 10 ml wound fluid simulation fluid (SWF), i.e. a 1: 1 solution of fetal calf serum and water with peptone (0.9% NaCl with 0.5% peptone). The flasks were shaken for about 10 seconds, after which the flasks were incubated at 35 ± 2 ° C. To measure the antimicrobial effect of the products, samples were taken every 24 hours for up to 8 days. The number of viable cells in the samples was determined using a standard plate count method.

[0073] The inventions and results of this experiment showed a more significant reduction in the number of viable Staphyocyte lococcus aureus cells by the silver containing foam of the invention than the other tested products (see Figure 5A). The reduction in viable cells of Pseudomonas aeruginos by Mepilex Ag was also greater than that of other products (see Figure 5B). The results are also shown in Tables 4A and 4B.

Table 4A: Prolonged antimicrobial effect on Staphylococcus aureus

<td>A sample</td><td>0 h logCFU / ml</td><td>24 h logCFU / ml</td><td>48 h logCFU / ml</td><td>72 h logCFU / ml</td><td>96 h logCFU / ml</td><td>120 h logCFU / ml</td><td>144 h logCFU / ml</td><td>168 h logCFU / ml</td>

<td>Control</td><td> 6,3</td><td> 8,6</td><td> 8,6</td><td> 8,3</td><td> 8,3</td><td> 8,2</td><td> 8,1</td><td> 8,1</td>

<td>A sample AND</td><td> 6,3</td><td> 5,1</td><td> 4,6</td><td> 3,2</td><td> 2,4</td><td> 2,0</td><td> 2,1</td><td> 2,0</td>

<td>A sample B</td><td> 6,3</td><td> 6,6</td><td> 5,5</td><td> 4,1</td><td> 3,5</td><td> 2,7</td><td> 2,6</td><td> 2,3</td>

<td>A sample C</td><td> 6,3</td><td> 6,2</td><td> 5,1</td><td> 4,5</td><td> 4,3</td><td> 4,3</td><td> 4,2</td><td> 4,6</td>

Table 4B: Prolonged antimicrobial effect on Pseudomonas aeruginosa

<td>A sample</td><td>0 h logCFU / ml</td><td>24 h logCFU / ml</td><td>48 h logCFU / ml</td><td>72 h logCFU / ml</td><td>96 h logCFU / ml</td><td>120 h logCFU / ml</td><td>144 h logCFU / ml</td><td>168 h logCFU / ml</td>

<td>Control</td><td> 6,52</td><td> 9,95</td><td> 9,48</td><td> 8,75</td><td> 8,55</td><td> 9,00</td><td> 9,13</td><td> 9,15</td>

EP 1 964 580 B1

<td>A sample</td><td>0 h logCFU / ml</td><td>24 h logCFU / ml</td><td>48 h logCFU / ml</td><td>72 h logCFU / ml</td><td>96 h logCFU / ml</td><td>120 h logCFU / ml</td><td>144 h logCFU / ml</td><td>168 h logCFU / ml</td>

<td>A sample AND</td><td> 6,51</td><td> 3,58</td><td> 2,26</td><td> 2,00</td><td> 2,00</td><td> 2,00</td><td> 2,00</td><td> 2,00</td>

<td>A sample B</td><td> 6,38</td><td> 6,55</td><td> 3,20</td><td> 2,95</td><td> 2,59</td><td> 2,00</td><td> 2,00</td><td> 2,00</td>

<td>A sample C</td><td> 6,35</td><td> 5,89</td><td> 5,90</td><td> 5,55</td><td> 6,03</td><td> 4,90</td><td> 5,49</td><td> 4,59</td>

[0074] The detection limit is 2.00 log CFU / ml.