WO2002087644A1

WO2002087644A1 - Wound dressings comprising a carboxymethyl cellulose fabric impregnated with honey

Info

Publication number: WO2002087644A1
Application number: PCT/GB2002/001989
Authority: WO
Inventors: James William Edmonds
Original assignee: Acordis Speciality Fibres Limited
Priority date: 2001-05-02
Filing date: 2002-05-01
Publication date: 2002-11-07
Also published as: GB0110715D0

Abstract

Wound dressings comprising honey also contain carboxymethyl cellulose filaments in amounts up to 50% of the weight of the honey, preferably in the form of a fabric.

Description

WOUND DRESSINGS COMPRISING A CARBOXYMETHYL CELLULOSE FABRIC IMPREGNATED WITH HONEY

Field of the invention

This invention relates to wound dressings and has particular reference to wound dressings comprising honey.

Backcrround of the invention

Honey has been used as a wound dressing for many hundreds, if not thousands, of years. With the rise of antibiotics, honey-based dressings somewhat fell out of favour but they are now of increasing interest, particularly honey- based dressings utilising Manuka honey. Manuka honey is honey produced by bees gathering exclusively or largely on the Manuka tree, Leptospermu scoparium. Leptospermum scoparium is a member of the genus Leptospermum. The genus contains about 86 species and is often commonly known as the tea tree. Honeys produced by bees gathering from other species of Leptospermum trees, such as L.polycralifolium, may also advantageously be used in the invention. One of the benefits of honey-based dressings is that they are almost perfectly benign although they may contain clostridial spores, which can be treated by gamma-irradiation.

It is believed that many of the honeys work by "tieing up" water molecules so that the bacteria have insufficient water to support growth (see for example the article "The Role of Honey in the Management of Wounds" by Molan P.C., Journal of Wound Care, September, Vol 8, No .8 , 1999, pages 415 to 418) . Molan notes that when used as a dressing the dilution of the solution of honey by the wound exudate reduces osmolarity to a level which ceases to control infection.

International patent application WO 00/09176 discloses a wound treatment composition comprising (a) an adsorbent material such as silica gel or anhydrous calcium chloride for adsorbing moisture on or around a wound and (b) a saccharide or polysaccharide or derivative thereof. The component (b) may be contained in honey. The adsorbent is characterised by its ability to retain moisture and not release it back into the wound. The adsorbent is differentiated from an absorbent (such as hydrocolloid gels) which absorbs moisture physically and can release moisture back into the wound once its absorptive capacity is reached (see page 2 lines 2-7 and 10-17 of WO 00/09176) . The composition is said to be preferably carried within an envelope in the form of a dressing, with at least part of the envelope being of a moisture-permeable material such as a non-woven heat-sealed cellulosic material (see page 10 lines 14-15 of WO 00/09176) . However, cellulosic materials on their own cannot be heat-sealed as cellulose chars or burns on heating and never melts, so that the meaning of this passage is unclear. It is apparent that this moisture-permeable material is intended to be unaffected by moisture, hence the need for the separate moisture-adsorbent material .

International patent application WO 01/41766, published on 14 June 2001 after the priority date claimed for the present application, discloses the use of honey in medical dressings, for example wound dressings, and also discloses the use of honey modified with a viscosity-increasing agent. Alginate is mentioned as a viscosity-increasing agent.

The present invention seeks to provide a honey-based wound dressing which does not rely on a particulate water- adsorbent material such as silica gel or calcium chloride nor on alginate-based materials as viscosity-increasing agents.

Disclosure of the invention

According to the present invention there is provided a wound dressing comprising honey, characterised in that it contains carboxymethyl cellulose filaments in an amount of up to 50% by weight of the weight of honey.

The wound dressings of the invention need not contain any water-adsorbent material such as silica gel or calcium chloride, nor is it necessary for them to include an alginate as viscosity-improving agent. The carboxymethyl cellulose filaments will take up moisture from the wound and can serve as a matrix onto which the honey is impregnated. Contrary to the disclosure in WO 00/09176, the inventor of the present invention considers that maintaining a moist environment for a wound assists in the creation of an environment in which the natural wound-healing process can proceed at the optimum rate.

The carboxymethyl cellulose filaments may be present in an amount in the range 1% to 20%, or 5% to 20% or 10% to 15%, preferably 10% or 15%, of the weight of the honey.

The honey is preferably a Manuka honey or a honey produced by bees gathering substantially from trees of the genus Leptospermum, particularly from L . scoparium or L . polygalifolium.

The wound dressing may be gamma-irradiated for sterilisation purposes . The carboxymethyl cellulose filaments are preferably formed by the carboxymethylation of lyocell cellulose filaments . The filaments are preferably formed into fabrics and preferably are nonwoven fabrics. The carboxymethyl cellulose filaments and the fabrics produced therefrom are preferably formed in accordance with the processes described in published PCT Application No. W0 94/16746, the contents of which are incorporated herein by way of reference. Lyocell is the generic name for the solvent- spun cellulose used as preferred starting material in WO 94/16746.

Preferably, the honey is incorporated into a carboxymethyl cellulose fabric by being applied to the fabric and being pressed into the fabric. The fabric may be backed by a non-absorbent layer. Preferably, the wound dressing is formed integrally with a packaging by producing a structure including a lower packaging layer, a wound dressing backing, a layer of carboxymethyl cellulose-containing fabric having applied thereto a layer of honey and an outer packaging layer, the layer of honey being pressed into the fabric by the application of the outer packaging layer and the outer packaging layer being sealed around its edges to the lower packaging layer, thereby producing a sealed product which can subsequently be gamma-irradiated for sterilisation.

The packaging layers, particularly the outer packaging layer in contact with the honey, preferably have a low contact adhesion to the honey. The layers may be made of polypropylene, polyethylene or polyvinyl chloride, for example .

Alternatively, the honey may be impregnated into a carboxymethyl cellulose fabric and subsequently immersed in a water-absorbent material, preferably ethanol, and then dried. It has been found that this reduced the stickiness of the dressing and the dressing can then be packaged, optionally with an occlusive backing.

By way of example, embodiments of the present invention will now be described with reference to the accompanying drawings, of which:

Figure 1 is a perspective view of a sample of carboxymethyl cellulose fabric;

Figure 2 is a perspective view of the fabric of Figure

1 impregnated within a central region with honey; Figures 3 and 4 are sectional views of Figure 2 along the line A, A;

Figure 5 is a perspective view of a dressing assembly prior to packaging; and

Figure 6 is a sectional schematic view of a dressing.

Figure 1 shows a fabric layer comprising a carboxymethyl cellulose fabric of nonwoven filaments, the filaments having been produced by the process described in the above mentioned W0 94/16746. The fabric layer 1 is in the form of a square dressing component having side dimensions of 10 cm and weighing approximately 1 gm.

Figure 2 shows the application to the central portion 2 of the fabric layer 1 a layer of honey weighing 10 gm. Typically, runny honey, otherwise known as clear honey, is used, containing about 18% water and 80% of natural sugars, by weight, the balance being minerals, vitamins, pollen and protein. Of the sugars just over 70% is fructose and just under 30% is glucose, by weight.

The honey may be applied to the fabric layer by pouring or impregnating the honey at locations within the area 2. The honey is then squeezed into the fabric to form an integral dressing by the application of pressure to the honey layer. This can be carried out by positioning the structure shown in Figure 2 on a plastic backing sheet such as a polyethylene sheet and applying a cover backing sheet - such as a further polyethylene sheet. The assembly is then squeezed together, for example by being passed through a roller to spread the honey within the dressing.

A cross section along the line A, A of the dressing shown in Figure 2 is shown in Figure 3. It can be seen that the honey is located within the region 3 but that the thickness of the dressing is substantially unaltered across its section. This means that, although the carboxymethyl cellulose fibres will absorb water and will gel, they are substantially unaffected by the just under 20% by weight of water in the honey and do not absorb significant amounts of moisture from the honey. It is not clear why the carboxymethyl cellulose filaments do not absorb the water and gel, as might be expected.

When water is applied to the dressing, to simulate what happens to the dressing in position on a wound, the carboxymethyl cellulose fibres absorb water and the entire dressing swells as shown in Figure 4. The importance of this is that, by absorbing the water, the carboxymethyl cellulose fibres permit the honey to remain at a higher concentration, the honey being located in the interstices between the filaments of the fabric, so that the honey concentration remains sufficiently high for the honey to remain active under conditions where it would become inactive in the absence of the carboxymethyl cellulose filaments .

Thus, the invention provides a wound dressing having a longer period of activity for the honey than prior art wound dressings which rely on honey alone.

A series of comparative tests was carried out to determine the effect of the incorporation of the carboxymethyl cellulose fabric into the honey, in particular to determine whether the carboxymethyl cellulose fabric would immediately gel when the honey was added to it and on the other hand whether it would gel subsequently in the presence of water. Alginate fabrics will gel only when sodium ions are present. Thus, if honey is incorporated into or reinforced with alginate fabrics then it would be expected that the absence of sodium ions in the honey would mean that the alginate would not gel. Alginate fabrics are, however, comparatively weak. Carboxymethyl cellulose fabrics, in particular carboxymethyl cellulose fabrics produced from carboxymethyl cellulose fibres having been made from lyocell, are, by comparison, quite strong. In fact, lyocell-derived carboxymethyl cellulose fabrics are almost as strong as lyocell fabrics themselves. However, unlike alginate, carboxymethyl cellulose will gel in water in the absence of sodium ions . This means that it might be expected that honey, which contains about 18% by weight water, might cause the carboxymethyl cellulose fabric to gel immediately. Carboxymethyl cellulose also gels extremely rapidly, which might be expected to prevent it having honey impregnated into it. Initial attempts were made, therefore, simply to squeeze honey into a carboxymethyl cellulose fabric, where the carboxymethyl cellulose fabric was produced from lyocell filaments. It was apparent immediately that, although the fabric went from substantially white to substantially translucent, this was more an optical effect produced by the incorporation of runny or clear honey into the fabric rather than any significant gelling of the fibres. This was confirmed under the microscope.

The conventional manner for measuring water absorbency of carboxymethyl cellulose samples is to weigh the sample, immerse the sample in an excess of saline solution for 30 minutes, lift the sample from the solution by a corner, let excessive water drip off, and then reweigh the sample to measure the weight gain. In a first series of tests, therefore, a sample of nonwoven fabric formed from carboxymethyl cellulose filaments produced from lyocell filaments in accordance with the disclosure of W094/16746 and having a basis weight of 100 gms/m² was cut into two sections. From the first section a 5cm x 5cm square of fabric was cut without any further treatment . In the case of the second sample a 10cm x 10cm square sample having a weight of lgm had dripped onto it lOgms of runny honey. The sample was then placed between a pair of polyethylene sheets and the sample was pressed so as to impregnate the runny honey into the fabric. A 5cm x 5cm square was then drawn on to the central area of one of the sheets and the sample then cut from that sheet .

Thus, two identical products were prepared and the fabric weight of the first sample was determined to be 0.25gm by calculation from the weight of the original. The overall weight of the sample was 5.38gms, thus the sample contained 5.13gms of honey. This was labelled Sample No.l. Sample No.2, the untreated fabric, was weighed and determined to have a weight of 0.27gm.

The two samples were then separately immersed in 0.9% by weight sodium chloride saline solution for 30 minutes. In each case the sample was immersed in 10.8gms of saline solution. The samples were left immersed for 30 minutes and then removed and drained for 30 seconds. The samples were then reweighed. The results of the tests are shown in Table 1 below:

From this Table it can be seen that both samples have increased in weight and visibly it could be seen that the carboxymethyl cellulose fibres in both had gelled. However, it was immediately apparent that much of the honey in Sample No.l had leached out of the dressing and could be seen in the remaining saline solution in the dish in which the sample had been treated. It was realised that this test does not represent a realistic representation of a dressing on a wound, as there would not then be such an excess of liquid in the wound and any honey leached out of the dressing would go straight into the wound.

In order to determine the effect of the honey on the swelling characteristics, and hence the absorbency, of the carboxymethyl cellulose fabric, tests were carried out to measure what effect the honey had on the swelling of the fabric in terms of its thickness.

Four samples were prepared from the same nonwoven fabric sample of carboxymethyl cellulose filaments as was used in the tests carried out above. The initial thickness of the fabric was measured at 1.72mm. Again the same loading of honey was impregnated into two samples and two samples were left untreated. The samples were each separately immersed in 10.8gms of 0.9% by weight sodium chloride saline solution for 30 minutes, removed from the solution and drip-dried for 30 seconds. The samples were then re-measured for thickness (in mm) and the results are shown in Table 2 below:-

It can be seen that both the fabric with the honey, Samples Nos .3 and 4, and the fabric without the honey, Samples Nos . 5 and 6 swell by very similar amounts . The filaments in the case of Samples Nos . 1 and 2 were virtually ungelled without the addition of the saline solution but after swelling both samples had filaments which had visibly gelled.

It will be appreciated that the carboxymethyl cellulose filaments may be in the form of staple fibres or continuous filaments. Preferably, the carboxymethyl cellulose filaments are wholly converted to carboxymethyl cellulose but it is not essential that this take place and it may be possible to use such filaments which are only partially converted from cellulose into carboxymethyl cellulose.

Instead of using a nonwoven fabric, other forms of fabrics such as knitted or woven fabrics could be used, or even simply filaments or fibres could be incorporated into the honey without any structure. However, it is probably preferable to use a fabric. Typically, a nonwoven fabric is a convenient method of incorporating the carboxymethyl cellulose filaments into the honey.

As used herein, the term runny honey or clear honey is used to characterise that type of honey as opposed to set honey. There is little difference between clear honey and set honey, it is principally a question of the balance of the natural sugar content of the honey between the fructose and glucose components . The balance of these two sugars effectively determines whether honey is clear (runny) or set. It is simply easier to incorporate the carboxymethyl cellulose into clear or runny honey than it is into set honey. However, all honeys will eventually transform from runny or clear honey into set honey and this is not detrimental to the invention.

Figures 5 and 6 illustrate one method of forming a backed wound dressing in accordance with the present invention. An initial layer of a packaging material 6 has mounted on it a backing layer 7 for a wound dressing. The backing layer 7 is preferably a waterproof layer, and the edge 8 of the waterproof layer may have an adhesive surface thereon for adhering the dressing to the skin. Located on the layer 7 is a layer 9 comprising a nonwoven fabric formed of filaments of carboxymethyl cellulose. A number of blobs of Manuka honey such as blobs 10,11 are then dropped onto the carboxymethyl cellulose fabric 9 by extrusion from a suitable dispensing apparatus. The next layer to be applied is a covering layer of non-adherent wound dressing material (not shown in Figure 5) . The wound absorbent backing material is applied as shown in Figure 6. The non-adherent covering layer is in the form of two portions 12 and 13 with the edge part of the portion 13 overlying a turned-back part 14 of the portion 12 of the covering layer to ease removal . An outer layer of packaging material 15 is then located over the entire dressing and the edges sealed as at 16. The assembly is then squeezed (pressed) to force the honey 10, 11 into the fabric layer 9. The thicknesses of all layers are shown considerably exaggerated in Figure 6 for purposes of explanation.

The assembly formed in Figure 6 can therefore be formed in a single manufacturing sequence and the assembly can be passed to gamma-irradiation for the purposes of sterilisation. Alternatively, the assembly illustrated in Figure 3 can be immersed in ethanol after impregnation and then dried in an air stream. It has been found that this reduces the stickiness of the dressing without removing a significant quantity of honey or affecting the properties of the dressing significantly.

It is fortuitous, that although the honey contains a certain water content (say 18-20% by weight) depending on the particular honey used, the honey when applied to the carboxymethyl cellulose does not cause the carboxymethyl cellulose filaments to gel or swell to any significant extent. However, the assembly of carboxymethyl cellulose filaments containing honey in the interstices is capable of absorbing moisture from a wound, and the carboxymethyl cellulose then absorbs a certain proportion of the water, maintaining the honey in an active concentration for longer than would be the case in the absence of the carboxymethyl cellulose filaments .

Furthermore, the carboxymethyl cellulose layer forms a gel which assists in removal of the dressing from the wound.

Thus, the utilisation of carboxymethyl cellulose filaments in honey provides for a honey-based dressing which has a longer effective life than in the absence of such filaments. Because the carboxymethyl cellulose is used in filamentary form it is not retained on the wound when the dressing is removed, and the dressing has a level of coherency, because of the filamentary nature of the carboxymethyl cellulose, which enables the dressing to be peeled off and disposed of after use without leaving significant quantities of either the honey or the carboxymethyl cellulose behind.

It is surprising that carboxymethyl cellulose, which will gel in the presence of water even in the absence of sodium ions, will absorb honey without gelling to such a significant stage as to render the dressing unviable. However, the carboxymethyl cellulose filaments, particularly those based on lyocell, have a sufficient strength to enable the dressing to be handled as an integrated whole even in the absence of the waterproof backing 7. The waterproof backing is, however, preferred on the basis that it enables the wound to be isolated from the exterior when the dressing is applied.

It will also be appreciated that the application of the dressing as illustrated in Figure 6 to a wound is straightforward and easy - the packaging layers 6 and 16 are peeled away, the nonadherent layers 12, 13 are removed and the dressing is simply stuck to the surrounding area of the wound via the adhesive layer 8 in a conventional manner.

Claims

1. A wound dressing comprising honey, characterised in that it contains carboxymethyl cellulose filaments in an amount of up to 50% of the weight of the honey.

2. A wound dressing as claimed in claim 1, characterised in that the carboxymethyl cellulose filaments are present in an amount in the range from 5 to 20% of the weight of the honey.

3. A wound dressing as claimed in claim 2, characterised in that the carboxymethyl cellulose filaments are present in an amount in the range from 10 to 15% of the weight of the honey.

4. A wound dressing as claimed in any one of claims 1 to 3, further characterised in that the honey is Manuka honey.

5. A wound dressing as claimed in any one of claims 1 to 4, further characterised in that the carboxymethyl cellulose filaments are in the form of a fabric.

6. A wound dressing as claimed in claim 5, further characterised in that the fabric is a nonwoven fabric.

7. A wound dressing as claimed in claim 6, further characterised in that the fabric has been treated with a water-absorbent material after formation and then dried.

8. A wound dressing as claimed in claim 7, further characterised in that the water-absorbent material is ethanol.

9. A wound dressing as claimed in any one of claims 5 to 8, further characterised in that the honey has been impregnated into the fabric integrally with the formation of a wound dressing package.

10. A wound dressing as claimed in any one of claims 1 to 9, further characterised in that the dressing has been gamma-irradiated after impregnation.