WO2007045931A2

WO2007045931A2 - Compositions and dressings for the treatment of wounds

Info

Publication number: WO2007045931A2
Application number: PCT/GB2006/050343
Authority: WO
Inventors: Stephen Cotton
Original assignee: Brightwake Limited
Priority date: 2005-10-22
Filing date: 2006-10-20
Publication date: 2007-04-26
Also published as: WO2007045931A3

Abstract

Compositions comprising from 30 to 99.5% w/w of honey and from 0.5 to 15% w/w of a naturally-occurring plant extract having anti-bacterial properties are useful in the treatment of wounds. The compositions may be applied directly to a wound or may be coated or impregnated onto a conformable substrate. Compositions comprising a concentrated solution of sugar in place of the honey may also be used.

Description

Title -Compositions and Dressings for the Treatment of Wounds

This invention relates to compositions and dressings that are useful for the treatment of wounds.

In the treatment of wounds, whether caused by injury or surgery, it is generally essential for dressings to be applied to the wound, commonly for prolonged periods. A wide variety of dressings, of numerous different types, are in use, and the choice of dressing will depend on a number of factors, including the nature and location of the wound, the presence or risk of infection and the amount of exudate produced, as well as factors such as the conformability of the dressing and its adhesive properties, and also patient-related factors such as the mobility and dexterity of the patient.

In general, the main reasons for the application of a dressing are:

to facilitate and accelerate healing of the wound; to prevent malodour; to minimise pain; to prevent or counteract infection; to absorb exudate.

In particular, wounds are susceptible to infection. The presence of microorganisms may inhibit healing and also lead to malodour. If untreated, such infection could become more serious and require treatment with systemic or topical antibiotics. Use of antibiotics can cause problems of skin sensitivity. The excessive use of antibiotics has also been implicated in the evolution of antibiotic- resistant strains of microorganism. For these reasons, measures which avoid the need for antibiotic treatment are highly desirable.

Wounds can be classified into several categories, of which one is sloughy wounds, that are characterised by a layer of viscous adherent slough. Such wounds often result from the formation of pressure sores, burns and leg ulcers. A thick layer of slough can build up rapidly on the surface of a previously clean wound, and in order to achieve an acceptable rate of healing, such wounds must be properly cleansed or "debrided".

Dressings that have been used in the treatment of sloughy wounds include sugar paste and honey dressings. Such dressings may take numerous forms, ranging from gels and pastes to impregnated pads. Sugar pastes have been prepared, in the simplest case, using ordinary granulated or icing sugar, those pastes being prepared immediately prior to use by simply mixing the sugar with water.

The high sugar content in sugar paste and honey dressings stops bacteria from growing.

As its name suggests, a honey dressing comprises natural honey. Honey is particularly effective in clearing infection from wounds because it has a number of additional properties that support wound healing, eg other natural antibacterial properties, a debriding action, an anti-inflammatory action, and a stimulatory effect on granulation and epithelialisation. The antibacterial properties of honey include the release of hydrogen peroxide, which is produced via a glucose oxidase enzyme reaction when the honey is diluted by wound exudates. Honey produced by bees that have gathered pollen from the flowers of the Manuka tree (Leptospermum scoparium) is believed to have particular antibacterial activity because it contains an additional antibacterial phytochemical component.

However, there are several disadvantages associated with both sugar paste dressings and honey dressings.

Being a natural material, honey is inevitably of variable composition, and this inevitably results in some variability in the characteristics and performance of dressings incorporating it. Only some Manuka honey is found to have significant antibacterial activity, the reasons for the variation in activity not being fully understood. Ad hoc preparation of sugar pastes is also accompanied by variability in performance. Furthermore, substantial amounts of sugar paste or honey need to be applied to a wound to achieve adequate potency. Both become very fluid at body temperature and even more fluid if diluted with proportionally small volumes of exudate. If a good therapeutic effect is to be obtained, it is therefore important that sufficient sugar paste/honey is applied to a wound and that it is retained in place. Bulky and heavy occlusive dressings are often required to prevent the sugar/honey oozing out of the wound.

There have now been devised improved compositions that are suitable for use as wound dressings, and which overcome or substantially mitigate the above- mentioned and/or other disadvantages of the prior art.

According to a first aspect of the invention, there is provided a composition suitable for use as a wound dressing, the composition comprising from 30 to

99.5% w/w of honey and from 0.5 to 15% w/w of a naturally-occurring plant extract having anti-bacterial properties.

According to a second aspect of the invention, there is provided a wound dressing comprising a conformable substrate coated or impregnated with a composition comprising from 30 to 99.5% w/w of honey and from 0.5 to 15% w/w of a naturally- occurring plant extract having anti-bacterial properties.

According to a further aspect of the invention, there is provided a method of treatment of a wound, which method comprises application to the wound of a composition comprising from 30 to 99.5% w/w of honey and from 0.5 to 15% w/w of a naturally-occurring plant extract having anti-bacterial properties, or application to the wound of a wound dressing comprising a conformable substrate carrying such a composition.

It has been found that the antibacterial properties of the compositions of the invention are substantially increased by the addition of the naturally-occurring plant extract with anti-bacterial properties. Also, the compositions are of more consistent antibacterial performance. Thus, wound dressings according to the invention are advantageous in that they are lighter and less bulky than conventional honey dressings whilst imparting an effective anti-bacterial action. The use of lower quantities of honey is also beneficial because problems of messiness are reduced. Compositions according to the invention may be effective in drawing exudate from the wound, whilst maintaining a moist environment at the wound site.

Honey may be present in the composition according to the invention at a level in the range of 20% to 80% w/w. In some embodiments, the honey is present at a level in the range of 30% to 60% w/w, or in the range of 40% to 50% w/w. In the presently most preferred compositions, honey is present at a level of about 45% w/w.

A wide variety of different types of honey may be used in the compositions according to the invention. However, it is preferred that the honey should be honey that includes naturally occurring antibacterial compounds. Manuka honey, ie honey produced by bees that have gathered pollen from the flowers of the Manuka tree, Leptospermum scoparium, is currently the preferred honey for use in the invention. The Manuka tree is indigenous to New Zealand and Manuka honey is widely produced in that country. Another form of honey that may be particularly useful in the present invention is that produced by bees that have gathered pollen from the flowers of Leptospermum polygalifolium, which is related to the Manuka tree and is native to Australia. The most preferred honey for use in the present invention is "UMF Manuka Honey", also called Active Manuka Honey. Active Manuka honey is sold with its activity rated on a "UMF" scale, the UMF (Unique Manuka Factor) being the equivalent concentration of phenol with the same antibacterial activity against Staphyloccuccus aureus (ie UMF 15 = 15% phenol). Preferred compositions according to the invention comprise Manuka honey with a UMF rating greater than 10, more preferably UMF 12 or above.

It is particularly preferred that the honey used in the composition according to the invention should be produced by bees that have gathered pollen from the flowers of the plant species that is the source of the plant extract having anti-bacterial properties. It is especially preferred that the honey used in the composition is Manuka honey and the plant extract is Manuka oil.

The honey used in the compositions of the invention may be regarded as a concentrated sugar solution. We have found that compositions prepared using sugar may also be useful in the present invention.

Thus, according to another aspect of the invention, there is provided a composition suitable for use as a wound dressing, the composition comprising a concentrated solution of sugar in water, and further comprising a naturally-occurring plant extract having anti-bacterial properties.

According to a related aspect of the invention, there is provided a wound dressing comprising a conformable substrate coated or impregnated with a composition comprising a concentrated solution of sugar in water and a naturally-occurring plant extract having anti-bacterial properties.

According to a yet further aspect of the invention, there is provided a method of treatment of a wound, which method comprises application to the wound of a composition comprising a concentrated solution of sugar in water, and further comprising a naturally-occurring plant extract having anti-bacterial properties, or application to the wound of a wound dressing comprising a conformable substrate impregnated with such a composition.

The composition may comprise in excess of 50% w/w of sugar. In some embodiments, the composition comprises in excess of 60% w/w, or in excess of 65% w/w, of sugar. Sugar solutions of such concentrations may have particularly beneficial effects on the wound, due to the low water availability and high osmolarity.

The nature of the sugar used in the composition is not critical. In preferred embodiments, however, the sugar is a mixture of glucose and fructose. It is particularly preferred for the sugar to be a standardised pharmacopoeial syrup, eg Sugar Syrup BP, which contains 70% w/w of sugar.

The naturally-occurring plant extract with anti-bacterial properties may be any one of numerous such extracts. Preferably, the extract is in the form of an essential oil, most preferably obtained by steam distillation.

One extract that may be used is Melaleuca alternifolia or Tea Tree oil. Another extract that may be used is Kunzea ericoides (Kanuka) oil. However, it is particularly preferred that the extract should be obtained from Manuka plants,

Leptospermum scoparium. The extract is most preferably obtained from the East Cape chemotype of L. scoparium, which is characterised by relatively low levels of pinenes and myrcene, but relatively high levels of flavesone, isoleptospermone and leptospermone. This particular strain of L. scoparium has particularly potent antimicrobial properties. In particular, L. scoparium has been shown to be active against both Gram-positive bacteria, eg Staphylococcus aureus, and Gram- negative bacteria, eg Escherichia coli, as well as being active against other forms of microorganism, eg yeasts such as Candida albicans and fungi such as Aspergillus niger. Another oil that may be used is so-called Lema oil, which is a blend of fractions from Manuka oil and Tea Tree oil.

The plant extract having anti-bacterial properties may be present in the composition according to the invention at a level of less than 10% w/w. In some embodiments, the extract is present at a level of less than 5% w/w, or less than 2.5% w/w, eg about 1% w/w or 2% w/w.

The compositions according to the invention, whether containing honey or sugar, may comprise additional ingredients to improve their physical properties such as flexibility and adherence. For example, it is desirable for a wound dressing to have some adherence to the skin on application, so that it stays in place, eg while additional bandages or tapes are secured in order to fasten it in place more permanently. However, it is also desirable that wound dressings are non-adhesive, so that they can be peeled away from the wound without causing damage.

Additional ingredients that may be present include glycerine and petrolatum (white soft paraffin). In some embodiments, glycerine is present in the composition at a level in the range of 5% to 50% w/w, or in the range of 10% to 30% w/w. In certain embodiments, glycerine is present at a level of about 20% w/w. In some embodiments, petrolatum is present in the composition at a level in the range of 5% to 75% w/w, or in the range of 10% to 50% w/w. In certain embodiments, petrolatum is present at a level of about 33% w/w.

Petrolatum may be used to reduce the concentration of honey or sugar in the composition, and may render the product less adherent. Glycerine may be used to alter the viscosity of the composition and so to facilitate its application to the substrate.

Further ingredients that may be incorporated into the compositions are swellable polymers that confer a degree of absorbency on the composition. A wide variety of such polymers are known, including notably cellulose derivatives such as carboxymethyl cellulose and salts thereof.

The compositions may comprise further active ingredients, normally in relatively minor proportions. For example, the compositions may contain Vitamin C or other vitamins, which may have a beneficial effect on the wound healing process. Such vitamins may be added in substantially pure form, or the compositions may include other ingredients, eg plant extracts, that comprise such vitamins. In addition to possible therapeutic benefits, the presence of such ingredients, eg lemon oil, may also confer on the composition an attractive aroma, which may also help to counteract malodour generated at the wound site.

The compositions of the present invention comprising sugar are normally prepared simply by mixing the anti-microbial plant extract, and any other optional ingredients, with a pre-prepared sugar/water mixture. Generally, such mixing will be carried out with agitation, eg stirring, to ensure uniform dispersal of the added ingredients.

The compositions comprising honey are normally prepared by mixing the anti- microbial plant extract with honey, and any other optional ingredients, at a raised temperature, typically between 30° and 70°C. Generally, such mixing will be carried out with agitation, eg stirring, to produce a uniform composition.

The dressings according to the invention comprise a conformable substrate that carries the compositions according to the invention. The substrate conveniently takes the form of a knitted fabric; in particular warp-knitted Viscose gauze. In other embodiments, the substrate may be a porous or absorbent pad, eg a mat of non-woven material. One particular material that is suitable for the pad is an alginate-based fibre material. Alginates are manufactured from different varieties of seaweed, and fibrous alginates commonly comprise calcium alginate fibre or sodium-calcium alginate fibre.

Honey-based compositions are preferably applied to the substrate while at elevated temperature. Where the composition contains one or more viscosity- reducing agents, eg glycerine, relatively low temperatures may be used. Where the viscosity is high, however, relatively high temperatures may have to be used in order to achieve uniform application of the composition.

In other embodiments, the composition comprises one or more gelling agents, the effect of which is to confer structural integrity on the product and hence eliminate the need for a substrate. Suitable gelling agents include pectins.

In use, a secondary dressing will in most cases be applied over the composition or dressing of the invention. Such a secondary dressing may take the form of an absorbent pad or bandage, or may be an occlusive dressing such as a film dressing. The invention will now be described in greater detail, by way of illustration only, with reference to the following Examples:

Example 1 : Honey-based Wound Dressing

Inαredients

L. scooarium honev 45% w/w

L. scooarium oil 2.0%

Petrolatum 33%

Glycerine 20%

Preparation

The composition is prepared by mixing the L. scoparium honey, L. scoparium oil, petrolatum and glycerine.

The composition may be coated onto sterile knitted Viscose gauze. The coated fabric should be visually uniform and reasonably free from clogged pores. An individual dressing may be formed by cutting the coated fabric to a convenient size, eg a 10cm square. Acetate liners may then be applied to each side of the dressing and it may be packaged in a conventional four-sided seal pack.

The product is gamma-irradiated at NMT 5OkGy using a Cobalt 60 source. Dosage must not be less than 35.OkGy to achieve a Sterility Assurance Level (SAL) of at least 10^"6.

Example 2: Sugar-based Wound Dressing

Ingredients

Sugar syrup BP 97.9% w/w L. scoparium oil 2.0%

Lemon oil 0.1% Preparation

The composition is prepared by mixing the L. scoparium oil and lemon oil into the sugar syrup BP.

The composition may be impregnated into a non-woven alginate pad.

Method of Use

Compositions such as those of Example 1 and Example 2 may be applied directly to a wound site as a paste. Alternatively, where the composition is impregnated into a pad, the impregnated pad is placed onto the wound surface. More than one such dressing may be placed next to each other in order to cover a large wound. A secondary dressing may then be placed over the pad(s). Depending on the tissue type within the wound bed, the level of exudate and the necessary frequency for change of dressing, the secondary dressing may be an absorbent pad and/or a film dressing or bandage. The dressing may require changing daily, particularly in the early stages of wound healing, but may be left in place for longer, eg up to 7 days, depending on exudate levels, any surrounding interstitial fluid, and oedema.

Claims

1. A composition suitable for use as a wound dressing, the composition comprising from 30 to 99.5% w/w of honey and from 0.5 to 15% w/w of a naturally- occurring plant extract having anti-bacterial properties.

2. A composition as claimed in Claim 1 , wherein the honey is a honey that includes naturally occurring antibacterial compounds.

3. A composition as claimed in Claim 1 or Claim 2, wherein the honey is Manuka honey.

4. A composition as claimed in Claim 3, wherein the Manuka honey has a UMF rating greater than 10.

5. A composition as claimed in any of Claims 6 to 9, wherein the honey is present in the composition at a level in the range of 20% to 80% w/w.

6. A composition as claimed in Claim 1 , wherein the honey is produced by bees that have gathered pollen from the flowers of the plant species that is the source of the plant extract having anti-bacterial properties.

7. A composition as claimed in Claim 6, wherein the honey is Manuka honey and the plant extract is Manuka oil.

8. A composition suitable for use as a wound dressing, the composition comprising a concentrated solution of sugar in water, and further comprising a naturally-occurring plant extract having anti-bacterial properties.

9. A composition as claimed in Claim 8, wherein the sugar is a mixture of glucose and fructose.

10. A composition as claimed in Claim 8 or Claim 9, where in the sugar is a standardised pharmacopoeial syrup.

11. A composition as claimed in Claim 10, wherein the sugar is Sugar Syrup BP.

12. A composition as claimed in any one of Claims 8 to 11 , wherein the sugar is present in the composition at a level in excess of 50% w/w.

13. A composition as claimed in any preceding claim, wherein the naturally- occurring plant extract with anti-bacterial properties is in the form of an essential oil.

14. A composition as claimed in any preceding claim, wherein the extract is obtained from Manuka plants.

15. A composition as claimed in any one of Claims 1 to 13, wherein the extract is obtained from Tea Tree plants.

16. A composition as claimed in any preceding claim, wherein the plant extract is present in the composition according to the invention at a level of less than

5% w/w.

17. A composition as claimed in any preceding claim, which further comprises glycerine, at a level of 5% to 50% w/w.

18. A composition as claimed in any preceding claim, which further comprises petrolatum, at a level of 5% to 75% w/w.

19. A composition as claimed in any preceding claim, which further comprises a swellable polymer.

20. A composition as claimed in Claim 19, wherein the swellable polymer is a cellulose derivative such as carboxymethyl cellulose and salts thereof.

21. A composition as claimed in any preceding claim, which further comprises a gelling agent.

22. A composition as claimed in Claim 21 , wherein the gelling agent is a pectin.

23. A wound dressing comprising a conformable substrate coated or impregnated with a composition as claimed in any one of Claims 1 to 20.

24. A wound dressing as claimed in Claim 23, wherein the substrate is a knitted fabric.

25. A method of treatment of a wound, which method comprises application to the wound of a composition as claimed in any one of Claims 1 to 22, or application to the wound of a wound dressing as claimed in Claim 23 or Claim 24.