WOUND DRESSING COMPRISING AN ANTIMICROBIAL COMPOSITION

Abstract

Methods, processes and compositions are provided for improved wound dressings comprising an antimicrobial composition. The wound dressings maintain conformability and strength, as well as antimicrobial performance, upon use after storage.

Claims

1. A process for preparing a packaged wound dressing including modified cellulosic fibres treated with an antimicrobial composition having a source of an antimicrobial metal ion and a quaternary cationic surfactant.

2. A method for maintaining conformability of a wound dressing, the method comprising providing a packaged wound dressing including modified cellulosic fibres treated with an antimicrobial composition having a source of an antimicrobial metal ion and a quaternary cationic surfactant.

3. The process of claim 1, comprising: modifying cellulosic fibers to obtain carboxymethyl cellulose; neutralizing the carboxymethylcellulose with an organic acid; adding a source of antimicrobial metal ion to the neutralized carboxymethylcellulose; washing the neutralized carboxymethylcellulose and the added source of antimicrobial metal ion to obtain a product; drying and processing the product into at least one nonwoven felt, and packaging the at least one nonwoven felt to provide a packaged wound dressing.

4. The process of claim 3, further comprising: subjecting the at least one nonwoven felt to at least one controlled environment; obtaining one or more samples from the at least one nonwoven felt subjected to the at least one controlled environment; measuring a tensile strength of the one or more samples in a machine direction along a length of the one or more samples, and measuring a tensile strength of the one or more samples in another direction transverse to the machine direction.

5. The process of claim 4, wherein subjecting the at least one nonwoven felt to the at least one controlled environment comprises: storing a first sample of the one or more samples in an ambient environment without any preconditioning; storing a second sample of the one or more samples in a dessicator in a zero humidity environment, and pre-conditioning a third sample of the one or more samples at a temperature of at least 23° C. and at a humidity of at least 55% RH such that the third sample has a moisture content of between 10% and 20% by weight.

6. The process of claim 5, wherein measuring the tensile strength of the one or more samples in the machine direction comprises: measuring the tensile strength of the first sample in the machine direction; measuring the tensile strength of the second sample in the machine direction; measuring the tensile strength of the third sample in the machine direction, and comparing the measured tensile strength of the first sample, the second sample, and the third sample in the machine direction.

7. The process of claim 6, further comprising determining the measured tensile strength of the third sample in the machine direction to be greater than the measured tensile strength of each of the first sample and the second sample in the machine direction.

8. The process of claim 5, wherein measuring the tensile strength of the one or more samples in the another direction transverse to the machine direction comprises: measuring the tensile strength of the first sample in the another direction; measuring the tensile strength of the second sample in the another direction; measuring the tensile strength of the third sample in the another direction, and comparing the measured tensile strength of the first sample, the second sample, and the third sample in the another direction.

9. The process of claim 8, further comprising determining the measured tensile strength of the third sample in the another direction to be greater than the measured tensile strength of each of the first sample and the second sample in the another direction.

10. The process of claim 3, wherein: neutralizing the carboxymethylcellulose with an organic acid comprises neutralizing the carboxymethylcellulose to a pH of at least 5.0, and adding the source of antimicrobial metal ion to the neutralized carboxymethylcellulose comprises adding at least 1% by weight silver ion to the neutralized carboxymethylcellulose.

11. The process of claim 10, wherein washing the neutralized carboxymethylcellulose and the added source of antimicrobial metal ion to obtain the product comprises: washing the neutralized carboxymethylcellulose and the added source of antimicrobial metal ion in a first wash solution containing EDTA, and washing the neutralized carboxymethylcellulose and the added source of antimicrobial metal ion in a second wash solution containing benzethonium chloride.

12. The method of claim 2, wherein providing the packaged wound dressing comprises: modifying cellulosic fibers to obtain carboxymethylcellulose; adding a source of antimicrobial metal ion to the carboxymethylcellulose; washing the carboxymethylcellulose and the added source of antimicrobial metal ion to obtain a product; drying and processing the product into at least one nonwoven felt, and packaging the at least one nonwoven felt to provide the packaged wound dressing.

13. The method of claim 12, wherein: adding the source of antimicrobial metal ion to the carboxymethylcellulose comprises adding at least 1% by weight silver ion to the carboxymethylcellulose, and washing the carboxymethylcellulose and the added source of antimicrobial metal ion to obtain the product comprises (i) washing the carboxymethylcellulose and the added source of antimicrobial metal ion in a first wash solution containing EDTA and (ii) washing the carboxymethylcellulose and the added source of antimicrobial metal ion in a second wash solution containing benzethonium chloride.

14. The method of claim 13, wherein: washing the carboxymethylcellulose and the added source of antimicrobial metal ion in the first wash solution comprises entraining EDTA, and washing the carboxymethylcellulose and the added source of antimicrobial metal ion in the second wash solution comprises maintaining benzethonium chloride on the product.

15. The method of claim 12, further comprising: subjecting the at least one nonwoven felt to at least one controlled environment; obtaining one or more samples from the at least one nonwoven felt subjected to the at least one controlled environment; measuring a tensile strength of the one or more samples in a machine direction along a length of the one or more samples, and measuring a tensile strength of the one or more samples in another direction transverse to the machine direction.

16. The method of claim 15, wherein subjecting the at least one nonwoven felt to the at least one controlled environment comprises: storing a first sample of the one or more samples in an ambient environment without any preconditioning; storing a second sample of the one or more samples in a dessicator in a zero humidity environment; pre-conditioning a third sample of the one or more samples at a temperature of at least 23° C. and at a humidity of at least 55% RH such that the third sample has a moisture content of between 10% and 20% by weight; pre-conditioning a fourth sample of the one or more samples at a temperature of at least 28° C. and at a humidity of at least 60% RH such that the fourth sample has a moisture content of between 10% and 20% by weight, and pre-conditioning a fifth sample of the one or more samples at a temperature of at least 38° C. and at a humidity of at least 70% RH such that the fourth sample has a moisture content of between 10% and 20% by weight.

17. The method of claim 16, wherein measuring the tensile strength of the one or more samples in the machine direction comprises: measuring the tensile strength of the first sample in the machine direction; measuring the tensile strength of the second sample in the machine direction; measuring the tensile strength of the third sample in the machine direction; measuring the tensile strength of the fourth sample in the machine direction; measuring the tensile strength of the fifth sample in the machine direction, and comparing the measured tensile strength of the first sample, the second sample, the third sample, the fourth sample, and the fifth sample in the machine direction.

18. The method of claim 17, further comprising determining the measured tensile strength of each of the third sample, the fourth sample, and the fifth sample in the machine direction to be greater than the measured tensile strength of each of the first sample and the second sample in the machine direction.

19. The method of claim 16, wherein measuring the tensile strength of the one or more samples in the another direction transverse to the machine direction comprises: measuring the tensile strength of the first sample in the another direction; measuring the tensile strength of the second sample in the another direction; measuring the tensile strength of the third sample in the another direction; measuring the tensile strength of the fourth sample in the another direction; measuring the tensile strength of the fifth sample in the another direction, and comparing the measured tensile strength of the first sample, the second sample, the third sample, the fourth sample, and the fifth sample in the another direction.

20. The method of claim 19, further comprising determining the measured tensile strength of each of the third sample, the fourth sample, and the fifth sample in the another direction to be greater than the measured tensile strength of each of the first sample and the second sample in the another direction.

Description

EXAMPLES

[0029] The following examples are illustrative of the present invention.

Example 1

[0030] Effect of moisture content on the tensile strength of silver containing wound dressings according to the invention.

[0031] Dressings according to the invention were prepared by modification of solvent spun cellulose tow to a degree of substitution of 0.3 to form carboxymethylcellulose, neutralising to a pH of 5.5 with an organic acid. Adding 1.2% cationic silver by an ion exchange process in a largely organic solvent such as by the process described in EP1343510, washing in an aqueous organic solution containing sodium chloride and di-sodium EDTA for light stabilisation and to entrain approximately 0.4% EDTA. Followed by washing in organic solvent wash containing fibre finishing agents including tween 20 and benzethonium chloride (to give 0.135% benzethonium chloride on the finished product). Warm air drying, cutting to staple and processing into a nonwoven felt by carding and a needle punching process. The dressings were cut to size from the felt and packaged in a light, moisture and vapour impermeable heat sealed foil pouch.

[0032] The dressings were removed from the packs and then subjected to various controlled environments.

Controlled Environments

[0033] Ambient as packed, tested without any preconditioning;

[0034] Zero humidity: Stored in a square desiccator with 3 perforated perspex shelves above a layer of silica gel desiccant, conditioned for a minimum of 5 days;

[0035] and the following by storing in humidity controlled rooms (Source Bioscience Ltd.) for a minimum of 6 days:

[0036] 25±2° C./60±5% RH

[0037] 30±2° C./65%±5RH

[0038] 40±2° C./75%±5RH.

[0039] Samples (ambient as packed) were tested immediately after opening the packs. Samples removed from the other environments were sealed into plastic bags during removal, and then tested immediately. The plastic bags (also preconditioned in corresponding controlled environments) were used to maintain the humidity of the environment of the samples until the point of testing.

Loss on Drying (LOD)

[0040] LOD of the samples was determined using the Ohaus moisture balance MB23 operated in accordance with the instruction manual. A sample mass of greater than 1 gram was used. Samples were cut to fit within the weighing pan, ensuring there was adequate clearance from the heating element. A standardised method was used with a maximum temperature limit of 110° C. The endpoint was determined automatically when the sample mass stopped reducing and was stable. Under these conditions the fabric did not char. Typically, samples would be subjected to a 10 minute cycle.

Fabric Thickness (Loft)

[0041] Samples were tested using the Hampden Soft Materials Thickness Gauge, Model FMTm1-4D, S/N 14082. Fabric thickness (sometimes referred to as loft) was determined for 6 dressings per batch.

Fabric Dry Tensile Strength

[0042] 2.5 cm×7.5 cm rectangular strips were cut from along the length (machine direction) and across the width (transverse direction) using a ribbon cutting die and press. Samples were conditioned as described in the table. The peak force and the extension at which that force occurred were recorded when a 50 mm test length was stretched at a constant separation rate of 100 mm per minute.

Results

[0043]

TABLE-US-00001 Relationship between absolute and relative humidity Pre-Conditioning 25° C./ 30° C./ 40° C./ Dry Ambient 60% RH 65% RH 75% RH Moisture (g/m.sup.3) 0.00 9.50 13.81 19.71 38.29 Thickness (mm) 0.170 0.190 0.198 0.183 0.202 LOD % 9.28 11.93 14.17 15.27 18.10 Tensile 3.10 5.19 5.80 5.36 7.75 Machine (N/cm) Tensile 5.15 6.53 11.12 10.23 14.28 Transverse (N/cm)

[0044] Loss on drying is the summation of all the volatile substances that can be removed by heating at 110° C. These include ethanol, water and to some degree acetic acid.

[0045] It is believed that water is the most critical of these to the successful production of gelling fibre products. Insufficient moisture leads to embrittlement which in turn leads to fibre breakage during fibre processing and the formation of dust. The subsequent reduced length stable fibre can then produce a weaker and lighter fabric with less loft which in turn leads to a lower absorbency product.

[0046] For this particular fibre, for this example, textile trials have shown that fibres for use in wound dressings according to the invention can be successfully textiled between 42% and 50% RH at around 18 to 20° C. Trials suggest that fibres with 10.5% to 11.5% w/w moisture content can be carded efficiently.

[0047] The results show that tensile strength, loft and LOD are all functions of equilibrium moisture content. The results suggest that fibres with a moisture content of greater than 10.5% will be able to be textiled to produce dressings suitable for use in the present invention.

Example 2

[0048] Effect of moisture content on conformability of examples of silver containing wound dressings according to the invention

Materials:

Test Dressings:

[0049] AQUACEL Ag, commercial product, absorbent, gelling, fibrous-felt dressing containing 1.2% w/w ionic silver.

[0050] Lot 1G 00157 5 cm×5 cm

[0051] Lot 1H 03025 10 cm×10 cm

[0052] Lot 1E 02908 15 cm×15 cm

[0053] AQUACEL Ag treated with an antimicrobial composition comprising di-sodium EDTA and benzethonium chloride during the addition of silver to the fibres.

[0054] Lot 1H 01291B 5 cm×5 cm

[0055] Lot 1H 01302B+C 10 cm×10 cm

[0056] Lot 1H 01303D 15 cm×15 cm Lot 1H 01251C+D 20 cm×30 cm

Methods:

[0057] The samples of AQUACEL Ag according to the invention, that is those treated with an antimicrobial composition comprising di-sodium EDTA and benzethonium chloride were produced by the method of example 1.

[0058] The resulting dressings were conditioned in a laboratory environment maintained at an average temperature of 20° C.±2° C. and an average relative humidity of 65% RH±4% for at least 24 hours prior to testing. The dressings had a moisture content as shown below.

[0059] Lot 1H 01291B 5 cm×5 cm LOD 12%

[0060] Lot 1H 01302B+C 10 cm×10 cm LOD 11%

[0061] Lot 1H 01303D 15 cm×15 cm LOD 11%

[0062] Lot 1H 01251C+D 20 cm×30 cm LOD 11%

[0063] The AQUACEL Ag dressings were similarly conditioned and packaged.

[0064] Dressing conformability was assessed using a panel of three laboratory staff who were given six samples each of the dressing according to the invention and correspondingly sized AQUACEL Ag as a comparator (or control). They wrapped each dressing around their forearm (in the dry state directly from the packaging) and scored how well each dressing conformed to the shape of the arm using a comparative score based on a five point system.

[0065] (A) much better than the comparator

[0066] (B) better than the comparator

[0067] (C) the same as the comparator

[0068] (D) worse than the comparator

[0069] (E) much worse than the comparator.

[0070] The results are given in the following table.

TABLE-US-00002 Flexibility Score Sample Details A B C D E Lot 1H 1302B 6 Lot 1H 1302C 1 5 Lot 1H 1302D 6

[0071] These results show that the dressings according to the invention were either equal to or better than the AQUACEL Ag which is known to have good conformability.