Composition

Abstract

A polyurethane foam wound dressing, the foam integrally comprising an oxidoreductase enzyme and a substrate for the enzyme. The foam is produced by mixing a polyurethane polymer, water, an oxidoreductase enzyme and substrate for the enzyme and drying the resulting product.

Claims

1. A polyurethane foam wound dressing, the foam integrally comprising an oxidoreductase enzyme and a substrate for the oxidoreductase enzyme, wherein the polyurethane foam has a swellability in water of 100% to 800%, and wherein the weight of the substrate for the oxidoreductase enzyme is 1% to 10% of the weight of the polyurethane foam wound dressing, and wherein the substrate for the oxidoreductase enzyme is provided as honey.

2. The foam wound dressing of claim 1, wherein the oxidoreductase enzyme is glucose oxidase and the substrate is glucose, or the oxidoreductase enzyme is fructose oxidase and the substrate is fructose.

3. The foam wound dressing of claim 1, wherein the foam has a density of at least 0.28 g/cm.sup.3 and comprises at least 0.1 mg enzyme per gram of foam.

4. The foam wound dressing of claim 1, wherein the foam is produced by mixing a polyurethane polymer, water, an oxidoreductase enzyme and a substrate for the oxidoreductase enzyme to produce a resulting product; and drying the resulting product.

5. The foam wound dressing of claim 4, wherein a monohydric alcohol and/or a rubber is added when producing the foam.

6. The polyurethane foam wound dressing of claim 1, wherein the foam is produced by mixing an isocyanate-capped prepolymer, water, methanol and an aqueous acrylic polymer emulsion to form a mixture and drying the mixture at between 60 C. and 100 C. for at least 5 minutes.

7. A method of treating a wound comprising applying the polyurethane foam wound dressing of claim 1 to a wound site.

8. The foam wound dressing of claim 3, comprising 0.1 mg to 1 mg enzyme per gram of foam.

9. The foam wound dressing of claim 3, comprising 5% (w/w) of substrate.

Description

FIGURES

(1) The wound dressing will now be further described by way of reference to the following Examples and Figures which are provided for the purposes of illustration only and are not to be construed as being limiting. Reference is made to a number of Figures in which:

(2) FIG. 1: Three foam samples; A. Polyurethane foam only, B. Polyurethane foam with honey, C. Polyurethane foam with honey and glucose oxidase. Only sample (C) containing both enzyme and substrate elicited a colour change in the hydrogen peroxide test strips. The other samples did not elicit a colour change.

(3) FIG. 2: The colour change elicited by Sample (C) indicated hydrogen peroxide levels generated to be approximately 1000 mg/l.

(4) FIG. 3: Analysis of hydrogen peroxide generation by polyurethane foam test samples. A. Samples of invention (upper) and control (lower) before hydration. B. Invention sample (upper) and control (lower) samples following hydration. C. Initial assessment of hydrogen peroxide generation from invention sample (upper) and control (lower) immediately post hydration indicates that all samples are generating >100 mg/l hydrogen peroxide. D. Scale used to assess hydrogen peroxide levels. E. Test strip assessment of invention samples at the 60 minute time point showing generation of 3-10 mg/l of hydrogen peroxide. F. Test strip assessment of control samples at the 60 minute time point showing no hydrogen peroxide generation.

EXAMPLES

Example 1

(5) Method

(6) Three prototype polyurethane foams were generated: A foam only, B foam with 5% (w/w) honey and C foam with 5% honey and glucose oxidase (5 mg in 50 g foam mixture), as follows:

(7) Mixing and spreading of the foam was conducted within a fume hood. Two pieces of casting paper were place onto the glass plate surface (or alternative hard perfectly flat surface) and the spreader bar was set to the desired height (typically 2.00 mm) and place on casting papers. De-ionised water 16.03 g, Primal 5.97 g and methanol 3.0 g was mixed in a disposable beaker. This water phase was added to Hypol 25.0 g and mixed. The mix was then poured straight away between two pieces of casting paper and spread to desired thickness thickness. The foam was then left to cure for 2-5 minutes and was considered cured when it did not break to the touch. The foam was dried in a fan assisted incubator oven set to 65 C. for 20 minutes to drive off excess water.

(8) To generate foam with 5% honey, 2.5 g honey was mixed with the de-ionised water, Primal and methanol.

(9) To generate the foam capable of generating hydrogen peroxide, 100 l glucose oxidase solution made from combining 100 l glucose oxidase solution (dH.sub.2O with 5 mg glucose oxidase) was mixed with 13.53 g de-ionised water, 2.5 g honey, Primal 5.97 g, and methanol 3.0 g in a disposable beaker. This water phase was added to Hypol 25.0 g, as described above. The water phase is added to the Hypol phase and mixed and the resulting mix was then treated as above (i.e. poured and spread to desired thickness thickness, cured and dried).

(10) Testing the Foam

(11) The foam prototypes (22 cm samples) were hydrated with 2 ml dH.sub.2O and incubated for 2 minutes to allow fluid to be absorbed. Following incubation hydrogen peroxide test strips (Peroxide 1000, Quantofix) were exposed to each sample for 15 seconds. Hydrogen peroxide test strips were compared against the Peroxide 1000 colour chart indicating the level of hydrogen peroxide present.

(12) Results

(13) Only the sample containing both enzyme and substrate (C) elicited a colour change in the hydrogen peroxide text strips (see FIG. 1). The colour change indicated hydrogen peroxide levels generated by prototype foam C to be approximately 1000 mg/l (see FIG. 2).

(14) It was surprising that the enzyme was still active following the manufacturing process. It was also surprising that the enzyme was able to form a complex with the substrate and therefore metabolise the substrate, despite the enzyme and substrate being integrated within the structure of the foam.

Example 2

(15) A further assessment was conducted on a test sample i.e. polyurethane foam containing honey and glucose oxidase incorporated during production (produced as described in Example 1) compared to a control polyurethane foam where no honey and glucose oxidase had been incorporated during production, but were applied to the surface of the foam.

(16) Three samples were taken (33 cm squares) from each of the foams. These samples were initially hydrated; the invention with 3 ml dH.sub.2O only and the control with 3 ml of dH.sub.2O containing glucose oxidase and honey (enzyme and substrate amounts in accordance with the invention). Samples were allowed to hydrate over a 2 minute period. All samples were then assessed over a 60 minute period with the foams rinsed every 10 minutes (50 ml dH.sub.2O for 1 minute). Hydrogen peroxide levels were assessed initially following hydration and then every 10 minutes following each rinse using test strips (QUANTOFIX Peroxide 100).

(17) Results

(18) The control and invention samples both successfully hydrated absorbing the 3 mls of fluid applied. Initial assessment of both samples indicated hydrogen peroxide generation at >100 mg/l (see FIG. 3C).

(19) Repeated rinsing of the control samples resulted in hydrogen peroxide levels diminishing. Hydrogen peroxide levels were maintained for the first 20 minutes, however these were seen to drop at the 30 minute time point. By 60 minutes no hydrogen peroxide was generated (see FIG. 3F).

(20) Hydrogen peroxide generation by the invention samples was significantly higher after 60 minute compared to control samples (see FIGS. 3E and 3F). Reduction in hydrogen peroxide levels generated by the invention samples was not observed until the 40-50 minute time points and by the 60 minute assessment the invention samples were still generating hydrogen peroxide at 3-10 mg/l (see FIG. 3E).

(21) This assessment highlights the benefits of inclusion of substrate and enzyme relevant for hydrogen peroxide generation directly into the foam, as opposed to addition of these elements post-manufacturing. Inclusion within the structure did not hinder hydrogen peroxide generation and was shown to provide benefits with regard prolonged production despite exposure to high fluid levels.