WO2002009782A1

WO2002009782A1 - Non-adhering wound dressings containing cyclodextrins

Info

Publication number: WO2002009782A1
Application number: PCT/GB2001/003369
Authority: WO
Inventors: Roger David Arnold Lipman
Original assignee: Avery Dennison Corporation
Priority date: 2000-07-27
Filing date: 2001-07-26
Publication date: 2002-02-07
Also published as: AU2002224598A1; GB0018471D0

Abstract

Compositions suitable for use as amorphous and/or other non-adhering wound dressings include an effective amount of cyclodextrin to confer odour absorbency. The cyclodextrin is preferably in aqueous solution for maximum odour absorbency. The absorbent composition preferably contains 5 to 70 weight percent of cyclodextrin, based on the other non-aqueous materials present, and may for example comprise a foam, an amorphous hydrogel, beads, granules, powder or a woven or non-woven pad.

Description

NON-ADHERING WOUND DRESSINGS CONTAINING CYCLODEXTRINS

The present invention relates to improved wound dressings, particularly to non-adhering and amorphous wound dressings that have odour absorbency. Patients in the community and in institutional settings such as hospitals and nursing homes often have or acquire chronic wounds, and these wounds can possess a very unpleasant odour. Odours from chronic wounds can be offensive both to carers and to family members of the patient . It is advantageous to reduce or eliminate these odours, and so contribute to the well being of the patient as well as that of the nursing staff and other patients. It is therefore an objective of the present invention to provide dressings that are able to absorb the odour arising from such wounds. 22222

Odour absorbent dressings for use in malodorous wounds such as leg ulcers, fungating carcinomas, faecal fistulae and pressure sores have traditionally used activated charcoal to adsorb the volatile materials responsible for the undesirable odours. The charcoal is normally present as charcoal cloth or in a web such as polyurethane foam impregnated with charcoal . The wound dressing sold by the Johnson and Johnson Company under the trademark Actisorb Plus^®, has such a charcoal cloth together with silver contained inside a non-adherent, spun- bonded nylon sleeve. Examples of other similar products are Carbonet^® from Smith and Nephew pic and Lyofoam C^® from Seton Scholl pic. Lyofoam C^® includes viscose fibres treated with activated charcoal encapsulated by a layer of polyurethane foam. However, charcoal is not the only odour absorbent material to have found use in dressings. GB-A-2259858 describes an absorbent of zeolite in a sachet for containing the odour of wounds. Again, EP 0 888 785 Al discloses odour absorbing wound dressings comprising porous absorbent polymer particles having an internal surface area of at least 500m²/gm. The preferred particles are made from porous, cross-linked polystyrene beads .

In a related field, EP-A-0509409 describes absorbent pads for retaining human faeces that include an odour absorbent comprised of a blend of basic and pH-neutral particles . The basic particles absorb acidic odour molecules and include inorganic salts such as carbonates, bicarbonates, phosphates, biphosphates, sulphates, bisulphates and mixtures thereof. The pH-neutral odour absorbent materials include activated carbon, clays, silicas, diatomaceous earth, polystyrene derivatives, zeolites, molecular sieves and starches. The preferred materials are sodium bicarbonate and synthetic zeolites, respectively. In addition, the absorbent can contain acidic particles such as citric acid and ascorbic acid to absorb alkaline vapours, such as the amines putrescine and cadaverine .

Dressings containing charcoal and other absorbents do not provigde a complete solution to the problem of malodorous wounds. Such products provide some odour control, but the black appearance of the charcoal dressings does not provide an elegant product, and has a poor psychological effect on patients and caregivers . Moreover, the absorption of odour by prior art products is often incomplete. This is because the absorbents are present in these products in the solid state, and absorption of odour molecules will depend then on diffusion of the offending molecules to vacant absorption sites on the surface of the absorbent . The rate of such diffusion, and hence the rate of odour absorption, will often be limited by the physical structure of the absorbent, and the make-up of the product containing it.

Non-adhesive wound dressings in the form of gauze pads have been known for over a century. Saline soaked gauze, sometimes referred to as a "wet-to-dry" dressing, has long been used to manage the exudate from chronic wounds. This mode of management is beset with problems for the caregiver and for the patient. First, the amount of wound exudate from chronic wounds can be as much as 1000 ml per day, and gauze is unable to absorb this quantity of fluid. Frequent dressing changes are therefore necessary. Second, the gauze becomes adhered to the healing tissues in the wound bed, which are then damaged on dressing removal, and the healing rate is slowed. These dressing changes and the accompanying wound damage are of course extremely painful for the patient.

Dressings pads made from alginate fibres were introduced in the early 1980 's in Europe. Alginate fibre is able to absorb large quantities of wound exudate forming a soft gel in the wound as it does so. The dressing is simply placed over the wound and covered with an absorbent pad. This soft gel can easily and painlessly be removed when it is saturated. A large number of branded alginate fibre dressing pad products are on the market, such as Sorbsan^® (Steriseal) , Kaltostat^® (ConvaTec) and Tegagel^® (3M) , and dressings made from combinations of alginate with other absorbent materials are also known.

Aquacel^®, marketed by ConvaTec Ltd, a Division of Bristol-Myers Squibb, is a soft, sterile hydrophilic non-woven ribbon dressing composed entirely of fibres of sodium hydroxymethyl cellulose which absorb wound fluid. Absorbed fluid is said to be retained within the fibre structure even under compression. As Aquacel^® absorbs exudate it is rapidly converted from a dry dressing to a soft, coherent gel. The dressing is covered with a secondary adhesive dressing to hold it in place.

Other dressings used for the treatment of chronic exuding wounds include foam products such as Lyofoam^® (Seton Scholl) , Allevyn^® (Smith and Nephew) and Tielle^® (Johnson & Johnson) . Lyofoam consists of a sheet of hydrophobic polyurethane, one surface of which has been treated to collapse the cells of the foam and allow it to take up fluid by capillarity. The dressing is freely permeable to moisture vapour and gases but resists the penetration of liquids due to the hydrophobic nature of the unmodified backing surface. When placed in contact with blood or exudate, the fluid is slowly drawn up into the wound contact layer and transferred laterally across the face of the dressing. The aqueous component then evaporates into the large cells at the back of the dressing from where it is lost to the atmosphere as water vapour. As this process continues, the cells in the facing layer become filled with cellular debris and solid material and the dressing itself becomes progressively more occlusive. The moist environment which is formed under the foam facilitates autodebridement, and it is a feature of this dressing that moist wounds with sloughy areas contain significant amounts of semi-liquid slough when the dressing is removed.

In contrast to the hydrophobic nature of Lyofoam^®, Allevyn^® is manufactured from hydrophilic polyurethane foam, backed with a polyurethane film and faced with an apertured polyurethane net which is designed to act as a non-adhering layer. The dressing, which was originally made available for the treatment of burns, is able to absorb large amounts of fluid, some of which is lost by evaporation through the film covering the top surface. Tielle^® also utilises a hydrophilic polyurethane foam as an absorbent for wound exudate. With Tielle^®, the absorbent pad is backed by an adhesive coated non-absorbent foam to hold it in place. Tielle^® is indicated for moderate to heavily exuding partial and full thickness wounds including venous ulcers, pressure ulcers, diabetic ulcers, donor sites, lower extremity arterial ulcers and second degree burns .

Dressing pads from hydrogels are also known. These tend to be used on chronic wounds where there is less exudate, or in wounds that have eschar or necrotic tissue that needs debridement . WO 98/17215 describes hydrogel dressings which are said to be highly absorptive, and that are comprise from 5 to 20 %wt of a polyurethane prepolymer, from 3 to 45%wt of propylene glycols and propylene glycols, and the balance water. Dependent claims of this specification reveal hydrogel dressings containing bacteriostatic agents that are said to control wound odour. Scherisorb Gel^® (Smith and Nephew) is a commercial product that also works according to this principle. The aqueous gel contains 0.8% metronidazole to control the anaerobic organisms responsible for the odour produced in certain types of wounds . In these cases odour control will occur through elimination of the bacteria responsible for the breakdown of material in the wound bed, and not by absorption of the molecules causing the offensive odour. This is not an effective means of odour control, since the amount and strength of any bacteriocide used will be limited by its damaging cytotoxic effect on the cellular processes responsible for healing.

Materials to fill or pack the deep cavity of especially chronic wounds are well known. Saline soaked gauze, which ^' has already been mentioned above, has been used for this purpose. Pharmaceutical gel preparations have also been used for a long time in the treatment of acute and chronic and other hard-to- heal wounds. In this regard, WO 84/00111 describes a heat sterilisable aqueous gel composition for use in the treatment of burns, cuts, wounds and abrasions. The composition contains a pharmaceutically acceptable glycol, preferably propylene glycol, and a cellulose derivative, preferably hydroxyethyl cellulose. The composition can optionally contain an antiseptic, antibiotic or topical corticosteroid.

GB 2,275,686 A describes swellable wound dressing materials formed from a humectant of one or more C_x - C₆ monohydric or polyhydric alcohols, combined with alginate esters of C_x - C₆ polyhydric alcohols. The compositions swell but do not dissolve in water. Insolubility is achieved by the addition of polyvalent cations such as calcium ions, or by covalent cross-linking of the alginate ester, or by adding gelatine or chitosan. Numerous other so-called amorphous hydrogels are on the market, such as Curasol^® (Kendall) , Duoderm^® Gel (ConvaTec) , Restore^® (Hollister) Intrasite^® Gel (Smith & Nephew) and MPM™ Hydrogel Dressing. These materials can be used in wounds for fluid donation, as well as for fluid absorption. In this way they can provide the moist wound healing environment required by granulation tissue, the autolytic debridement required by yellow sloughy tissue, and the hydration required by black necrotic tissue, as well as absorbing exudate .

A hydrogel for use as a wound dressing is described in PCT Application No. WO 92/16245, which consists of water insoluble, water swellable cross-linked cellulose derivative, water and a polyol component. The gel described in this publication is primarily directed to the removal of necrotic tissue, as it reduces the need for use of a chemical debriding agent or surgical excision. The gel thus provides a dressing which can combine the actions of debriding and cleansing, independent of the extent of necrosis. Furthermore, the dressing is capable of breaking down necrotic tissue and retaining debris. PCT Application WO 98/40110 discloses a gel for use in dressing a wound and a process for its manufacture. The gel comprises a monovalent salt of a polygalacturonic acid derivative such as sodium pectate, a carboxypolysacharide such as a monovalent salt of a carboxycellulose derivative or a monovalent salt of an alginic acid derivative, and multivalent ions providing cross-links between the monovalent salt and the carboxy-polysaccharide . Again, EP 0 048 558 A2 teaches a resorbable gel of, for example gelatine, containing a water soluble medicament as a means of treating an infection in a cavity in bone or other tissue. The gel may also be in the form of a solid rod, or other three dimensional shape.

Intrasite^® Cavity Wound Dressing (Smith and Nephew) consists of small chips of hydrophilic polyurethane foam, totally enclosed within a thin conformable plastic pouch which is perforated to permit the uptake of wound exudate. The dressing is available in a range of different shapes and sizes and is said to be highly absorbent.

In 1975 a new treatment was reported in Brit. Med. J. 3 , 131-133, (1975) which involved the use of silicone foam dressing. The dressing is formed in si tu from two liquids which are carefully measured out in the correct proportions and mixed thoroughly before introduction into the wound. The chemical reaction produces hydrogen gas which causes the mixture to foam up to about four times its original volume before it sets to a soft, open cell absorbent foam stent that occupies the full volume of the wound cavity.

A solid, soluble granular material to be used in conjunction with occlusive hydrocolloid adhesive dressings for the packing of wounds is disclosed in US Patent 4,538,603 to Squibb. Wounds emitting a large amount of fluid can be treated by first packing them with the granular material and then covering the wound with the occlusive dressing. The preferred composition of granules appears to be that containing equal weights of pectin, gelatine and sodium carboxymethyl cellulose.

Hydrophilic polyurethane gel foams are described in US Patent 5,844,013. These are used particularly in the management of deep wounds and wound cavities. A haemostatic wound dressing is described in US Patent 5,836,970 that comprises a blend or mixture consisting of effective amounts of chitosan and alginate . The chitosan and alginate are present in a weight ratio within the ranges of about 5:1 to 1:5, and are present in a form selected from the group consisting of a multilayered composite, a powder, a composite fibre, a film, a gel, a foam, or a mixture thereof.

It is an object of the present invention to provide non- adhering wound dressings that provide control of the odour often associated with the management of difficult and chronic wounds. It is a further object of the present invention to provide amorphous dressings, granules and other forms for filling and/or packing of cavity wounds that are also absorbent of wound odours. It is yet a further objective of the invention to provide non-adhesive dressing pads that have improved wound odour absorbent characteristics.

By the term "non-adhering wound dressing" is meant all wound dressing materials that (a) are not pressure sensitive adhesive, and either (b) prior to application to the wound comprise an "aqueous medium" , an aqueous suspension, an aqueous gel and/or a solution of the absorbents, or (c) contain or comprise absorbents which absorb an "aqueous medium" including wound exudate. Here, the word "absorbent" refers to absorbents of wound exudate as well as of odours.

In the above paragraph, it will be understood that this definition of a "non-adhering wound dressing" is taken to include a dressing construction consisting of, for example, a non-adhesive and non-adhering "island pad" that is surrounded by a pressure sensitive adhesive coated film, foam, fabric etc. to hold the pad in place. It will be further understood that the term "aqueous medium" refers both to water initially present in the product on application to the wound, and to water absorbed by the product in the form of wound exudate.

It has been discovered that inclusion of an effective amount of a cyclodextrin in compositions suitable for use as amorphous and/or other non-adhering dressings confers odour absorbency on the compositions. Cyclodextrins are both naturally occurring and synthetically derived macrocyclic molecules that are characterised by having a toroidal shape, like a doughnut. It is believed that these toroidal shaped molecules absorb odiferous molecules by complexing them within the hole defined by the toroid. Further, this absorption occurs most easily in the presence of water, when the cyclodextrin is in solution. In this way all cyclodextrin molecules are potentially available for odour absorption, provided sufficient water is present to solvate the toroids . This is in contradistinction to the situation with the other odour absorbent systems described in the prior art, which do not need the presence of water, but are consequently incompletely available for absorption. Thus, cyclodextrins provide an improved means for the absorption of wound odours . This invention contemplates modification of all types of "non-adhering wound dressing" with cyclodextrins. Thus, foam dressings of the Lyofoam^® and Allevyn^® type can be impregnated with cyclodextrins during manufacture . Soluble powder and granular dressings can include powdered cyclodextrins in the formulation, amorphous hydrogels can be formulated to contain cyclodextrins, hydrophilic polyurethane gel foams can be modified to contain cyclodextrins, and so on. It is not necessary that the cyclodextrin is initially completely in solution within the dressing, only that either at least a portion of it is dissolved in the initial aqueous medium, and/or that it dissolves in the wound exudate after absorption of the latter during use .

The use of cyclodextrins in cosmetics as odour absorbing agents and as vehicles to deliver active ingredients to, for example, the skin, is known in the literature. For example, PCT Application WO 99/06078 discloses cyclodextrin odour absorbent articles for decreasing odours associated with body fluids, where the cyclodextrin has a specific particle size. PCT Application WO 98/56890 teaches the combination of aqueous cyclodextrin compositions with wrinkle control agents for odour and wrinkle control of fabrics. PCT Applications WO 98/17239, WO 98/17240, WO 98/56341 and WO 98/56342 describe an aqueous carrier containing soluble cyclodextrins, perfume compositions and preferably hydrophobic antimicrobial compounds in order to reduce body odour and or environmental odour. PCT Applications WO 98/18439 and WO98/56340 reveal similar compositions in a powder carrier such as a starch. PCT Application WO 98/56339 describes similar compositions in a two-phase formulation comprised of an aqueous phase and an oil phase .

US Patent 5,429,628 and PCT Application WO 94/22501 both teach the preparation of articles containing small particle size cyclodextrin for odour control . A large number of consumer absorbent products, such as panty liners, catamenials, diapers and sanitary napkins are exemplified, where the cyclodextrin is present within, or as part of, a fibrous absorbent medium.

European Patent Specification 0 392 608 Bl concerns solid consumer product compositions containing an ingredient such as a flavour, a drug or a perfume that is complexed within a cyclodextrin. Product categories that are mentioned include those such as drinks and beverages, canned pet foods, cosmetics and toiletries such as facial scrubs, body powders, depilatories, mouth washes and lipsticks, detergents, paper towels, cake mixes and cookies, incense, room deodorant blocks, dyes, insect repellents and the like.

US Patent 5,246,611 and PCT Applications WO 93/05136 and WO 91/17300 all deal with the use of cyclodextrin perfume complexes in fabric treatment products such as fabric softeners . The cyclodextrin complexes are suspended in polyalkylene glycol carrier that does not prematurely displace the active from the cyclodextrin.

According to a first aspect of the invention, there is provided a non-adhering wound dressing containing an effective amount of a cyclodextrin, that absorbs wound exudate and wound odour. Dressings according to this aspect of the invention may be applied to wounds in the form of foams, amorphous hydrogels, beads, granules, powders, woven pads, non-woven pads, etc., indeed in any form wherein the wound contacting surface is not pressure sensitive adhesive. The cyclodextrin may be present as a solution within the dressing, or as a powder or other form that eventually at least partly dissolves in the aqueous medium absorbed by the dressing from the wound.

The amount of cyclodextrin in the composition is preferably from 5 to 70 wt.%, more preferably 10 to 50 wt.%, based on the other non-aqueous materials present.

A further aspect of the invention relates to dressings that absorb wound odour and that are capable of donating fluid to a wound. These dressings may be in the form of foams, amorphous hydrogels, beads, granules, powders, woven pads, non-woven pads, etc., indeed in any form wherein the wound contacting surface is not pressure sensitive adhesive. This aspect of the invention requires the dressing to comprise an aqueous component on application to the wound, and an effective amount of a cyclodextrin at least partially dissolved in the aqueous medium prior to application.

One preferred embodiment of the invention takes the form of a dressing structure that can deliver a fragrance to the wound, preferably in the form of a fragrance complexed in a cyclodextrin. Such structures will also absorb odours from wounds, but the simultaneous delivery of a fragrance can be beneficial in that it provides an olfactory signal to the patient that management of odour is underway. Careful choice of fragrance is necessary to ensure that no chemicals are introduced into the wound environment that negatively impact healing rate, but this is facilitated by complexing the fragrance molecules in cyclodextrins, from which they will be released slowly and in a controlled way.

Non-limiting examples of foam materials suitable for use as carriers for cyclodextrins include polyurethane foams, silicone foams. These foams may be closed cell structures or reticulated and open in structure or a combination of the two, i.e. a semi-open cell structure.

Hydrogel pads may be formed for example from polyurethanes, acrylic polymers containing at least a proportion of hydrophilic monomers such as hydroxyethyl methacrylate, ethylene oxide polymers etc. According to one embodiment an acrylic polymer is dissolved in a suitable solvent such as ethyl acetate, polyethylene glycol is added and the cyclodextrin is then added, dispersed in a suitable carrier such as propane 1,2-diol.

Granules and powders may include those cited above composed of a mixture of pectin, gelatine and sodium carboxymethyl cellulose. Other suitable hydrocolloids for use in granules and powders in conjunction with the cyclodextrins are naturally occurring hydrocolloids such as guar gum, karaya gum, locust bean gum, carageenan, tragacanth gum, alginates, xanthan gum, modified naturally derived substances such as sodium carboxymethyl cellulose, synthetic materials such as polvinylalcohol, polyoxyalkylene polyols, polyvinyl pyrollidone, and animal derived materials such as gelatine. Ionic hydrocolloids such as hyaluronic acid, chitosan salts or DEAE Dextran may also be employed. The hydrocolloids may be water absorbable or water swellable, and combinations of one type or of various types may be used in any ratio.

In one preferred embodiment, sodium polysaccharides such as sodium pectate and/or sodium carboxymethyl cellulose are cross-linked by the addition of a divalent cation, for example calcium chloride.

Examples of beads include dextranomer beads such as Debrisan^® .

Amorphous hydrogels suitable for reduction to practice of the present invention include those for example based on the hydrocolloids cited above, as well as for example those based upon acrylic polymers. Generally, the amorphous hydrogel will be based upon a cross-linked polymer. In this way, the gel will leave no residue in the wound after removal.

Examples of absorbent non-woven pads include those based upon alginate fibres, and also those based on conventional fibres such as polyester, polyamide, polypropylene and so forth. Similarly, woven and knitted structures may be employed.

The term cyclodextrin, as used herein, includes any of the known cyclodextrins. Cyclodextrin materials are cyclic oligosaccharides containing a minimum of six D- (+) - glucopyranose units attached by - (1 > 4) glucosidic bonds. Three cyclodextrins called oc, β and γ are naturally occurring and have, respectively, six, seven and eight glucose units. Cyclodextrins are known that contain up to twelve glucose units . Cyclodextrin materials can also be manufactured from starch by enzymatic degradation. In addition, many synthetic modifications of the natural material materials are known, for example methyl-β-cyclodextrin and hydroxypropy1-β- cyclodextrin. The conformations of the cyclic structures of these molecules are such that the molecules are arranged in rigid conical molecular shapes that have hollow interiors of very well defined sizes. These internal cavities are hydrophobic in nature because the interior of the toroidal shape is predominantly made up of hydrogen atoms. The interior shapes of the cyclodextrins are able to form inclusion complexes, sometimes referred to as "host-guest" complexes, or clathrate compounds, with organic molecules which fit, completely or partially, into the cavities defined by the toroidal shapes. For example, odiferous molecules can fit into the cavities. This includes both perfumes and malodorous compounds. Cyclodextrins therefore, and especially mixtures of cyclodextrins with cavities of different sizes, can be used to control odours. With respect to odour control, there is scope for two different approaches within the present invention. First, uncomplexed or free cyclodextrins, dispersed within the adhesive matrix, can be used to absorb malodours. Second, perfumes can be precomplexed with cyclodextrins and then formulated in the final product . The perfume is then released in si tu and will mask the undesirable odour. (Once a cyclodextrin molecule has released its precomplexed perfume molecule, it is then available to complex a malodorous molecule) . The complexation of odorous molecules by cyclodextrin and the release of precomplexed perfume molecules from cyclodextrin are facilitated by the presence of water. It will be understood that the water necessary to facilitate such release of perfume and complexing of malodour by the cyclodextrin is initially present in the amorphous hydrogel or other non-adhering dressing, or is eventually acquired by the absorption of wound fluid.

The choice of cyclodextrin employed in a given formulation will be decided on the basis of the properties desired in the finished product, and the specific role that the cyclodextrin is fulfilling. Unmodified β-cyclodextrin is not very water soluble and is generally not preferred if high absorbency is needed, α-cyclodextrins, γ-cyclodextrins and certain modified β-cyclodextrins are more water absorbent. Mixtures of cyclodextrins are often preferred, because these will absorb a wider range of malodorous molecules than will a single cyclodextrin. The cyclodextrin to be used for a specific product will of course be determined in part by the size and shape of the odour molecules to be complexed.

Active ingredients may added to the formulations anticipated by the instant invention. By active ingredient, we mean an ingredient that is not essential to the functioning of the formulation as an exudate absorbing, moisture donating, odour absorbing or odour masking dressing composition. An active ingredient is added to confer an additional benefit to the formulation. It will generally be advantageous if the active ingredient first is complexed with a cyclodextrin prior to mixing into the formulation. However, it is not necessary that the active ingredient is first complexed, nor indeed that it complexes with a cyclodextrin at all. As non-limiting examples of active ingredients may be cited antimicrobial compounds, antibiotics, topical anaesthetics and growth factors such as for example epidermal growth factors . Active ingredients must be present at sufficient concentrations to achieve the desired effect, preferably at least 1 or 2 wt.%. In general, however, active ingredients will be present usually at no greater than 10wt%, and preferably at no greater than 5wt%, with respect to the total composition. Further optional materials may be added to the formulations such as for example plasticisers, and pigments.

The invention will now be further illustrated by way of the following non-limiting examples.

Examples 1 and 2

These two examples illustrate the production according to the invention of wound treatment gels incorporating cyclodextrins .

In accordance with the teachings of PCT Application WO 98/40110, 1.5kg of sodium pectate powder (Citrus Colloids Ltd) and 2.0kg of sodium carboxymethyl cellulose powder, grade 7H3SXF (Hercules Ltd) are separately dissolved each in 20kg deionised water, and the two solutions are mixed to give a homogeneous solution. Calcium chloride powder 0.5kg (Aldrich) is dissolved in a further 2.5kg deionised water, and a gel is produced by adding the calcium chloride solution stepwise with continual mixing to the combined solution of the two polysaccharides . The sodium ions of the polysaccharides are displaced by the calcium ions to give ionic cross linkages . A mixture of cyclodextrin molecules, 50 wt% each of hydroxypropyl-β-cyclodextrin, (Cavitron 82005, Cerestar Benelux BV) and γ-Cyclodextrin (Gamma W8, Wacker Chemie GmbH), is then dispersed in propane 1:2 diol 7.8kg (Aldrich) and this dispersion is added to the formulation. A wound treatment gel having the added benefit of odour absorption is produced. In the two examples, the total weight of the two cyclodextrins in the formulation is adjusted to be respectively 10wt% and 50wt% of the weight of the other carbohydrate molecules present .

The gel formulations, which have the following compositions, can be packaged in tubes or sachets and sterilised by steam at 121°C for 20 minutes.

Example 3.

This example illustrates the incorporation of cyclodextrin into a thermoplastic hydrogel polymer suitable for impregnating a fibrous wound contacting substrate such a cotton gauze or alginate fiber. A solution of N,N-dimethyl acrylamide (32.175gm) (Aldrich Chemical) and polystyrene methacrylate macromonomer of molecular weight 13000 (0.825gm ) (Sartomer) in ethyl acetate (67ml) is placed in a flask, and azobisisobutyronitrile (0.033gm) (Aldrich Chemical) dissolved in ethyl acetate is added with stirring. The flask is heated at 50°C for one hour and then at 80°C for a further two hours. After the three hours reaction time the contents of the flask are cooled and the polymer is precipitated by pouring the solution slowly into diethyl ether (200ml) . The polymer is washed with diethyl ether and dried under vacuum. The graft copolymer is redissolved in ethyl acetate, and polyethylene glycol PEG 400 (27gm) (Aldrich) is added. Hydroxypropyl β- Cyclodextrin (Cavitron 82005) (lOgm) (Cerestar Benelux BV) is added to the solution with stirring and the homogeneous mixture is cast over a piece of cotton gauze contained in a folded tray of silicone release paper. The sheet is dried in a vacuum oven at room temperature followed by drying at 50°C for ten hours . The copolymer sheet is immersed in water to give a clear, hydrated, reinforced hydrogel/gauze composite containing the hydroxypropyl β-Cyclodextrin, which is then cut into sheets 10 x 10cm, packaged and sterilised at 25 KGy with gamma radiation, and used as dressings for odiferous wounds.

Example 4.

This example illustrates the incorporation of cyclodextrin on to the surface of a fibrous, thermoplastic hydrogel impregnated wound contact composite material .

A solution of N,N-dimethyl acrylamide (32.175gm) (Aldrich Chemical) and polystyrene methacrylate macromonomer of molecular weight 13000 (0.825gm ) (Sartomer) in ethyl acetate (67ml) is placed in a flask, and azobisisobutyronitrile (0.033gm) (Aldrich Chemical) dissolved in ethyl acetate is added with stirring. The flask is heated at 50°C for one hour and then at 80°C for a further two hours. After the three hours reaction time the contents of the flask are cooled and the polymer is precipitated by pouring the solution slowly into diethyl ether (200ml) . The polymer is washed with diethyl ether and dried under vacuum. The graft copolymer is redissolved in ethyl acetate, and polyethylene glycol PEG 400 (27gm) (Aldrich) is added. A piece of cotton gauze is dipped into the solution, the gauze is squeezed out and the moist gauze is sprinkled with hydroxypropyl β- Cyclodextrin powder (Cavitron 82005) (5gm) (Cerestar Benelux BV) . The gauze is dried in a vacuum oven at room temperature followed by drying at 50°C for five hours. Thus the gauze fibres are coated with an absorbent hydrogel, on the surface of which is the hydroxypropyl β-Cyclodextrin. After drying, the pad is packaged in a peel pouch and is sterilised at 25 - 35KGY in a gamma irradiation facility to give a sterile dressing suitable for application to an exudating, malodorous wound.

Examples 5 and 6

These examples show the use of cyclodextrin to create odour absorbing wound treatment granules .

Example 5

To 1.2kg of a mixture of equal parts hydroxypropyl β- Cyclodextrin powder (Cavitron 82005), pectin (USP100, Hercules Chemical) and sodium carboxymethylcellulose (7H3SXF, Hercules Chemical) is added 500ml of distilled water or a mixture of distilled water and ethanol. Mixing is performed in a rotating oscillating mixer to give a homogeneous blend. The blend is sieved through a course sieve (0.5in.) and the moistened material is dried at 55°C for 24 hours. The dried material is milled and sieved to give a granular material of between 16 and 20 mesh size. The granules are packed in a small tray with peelable lidding and sterilised with gamma radiation having a dose between 25 - 35KGY. The granules are used to pack the cavity of an exuding venostasis ulcer (leg ulcer) on the lower left leg of a 73 year old Caucasian male which is then covered with an occlusive dressing (Duoderm Hydrocolloid Dressing) . The granules of the present Example interact with the wound exudate to form a gel like mass, which is able to absorb the odour emanating from the wound, and to prevent leakage of exudate through the dressing. When commercially available non-cyclodextrin containing granules (Duoderm Hydrocolloid Granules) are used to pack a similar wound on the right leg of the same patient, and then covered with the same dressing (Duoderm Hydrocolloid Dressing) , odour is detected from the wound.

Example 6.

In a similar fashion to example 5, to 1.2kg of a mixture of equal parts hydroxypropyl β-Cyclodextrin powder (Cavitron 82005) , γ-Cyclodextrin powder (Gamma W8, Wacker Chemie GmbH) , and sodium carboxymethylcellulose (7H3SXF, Hercules Chemical) is added 500ml of distilled water or a mixture of distilled water and ethanol. After mixing, the blend is sieved, dried and milled and sieved again to give a granular material of between 16 and 20 mesh size, exactly as in Example 4. The granules are packed in a small tray with peelable lidding and are sterilised with gamma radiation having a dose between 25 - 35KGY. The granules of the present Example interact with the wound exudate to form a gel like mass, which is able to absorb the odour emanating from the wound, and to prevent leakage of exudate through the dressing.

Summary

The present invention relates to various types of non- adhering wound dressing materials, such as amorphous gels, granules and non-adhering pads, which contain an effective amount of a cyclodextrin. Such compositions confer odour absorbency on dressings made from them, which is particularly useful for managing certain especially chronic wounds .

Claims

CLAIMS :

1. A non-adhering wound dressing which comprises an absorbent composition containing a cyclodextrin in an amount effective to absorb wound odour.

2. A wound dressing according to claim 1 wherein the absorbent composition contains 5 to 70% by weight, based on other non-aqueous materials present, of cyclodextrin.

3. A wound dressing according to claim 2 wherein the absorbent composition contains 10 to 50% by weight, based on other non-aqueous materials present, of cyclodextrin.

4. A wound dressing according to any preceding claim wherein the cyclodextrin is selected from α-cyclodextrins, modified or unmodified β-cyclodextrins, γ-cyclodextrins and mixtures thereof.

5. A wound dressing according to any preceding claim wherein the cyclodextrin is present as a solution within the dressing.

6. A wound dressing according to any one of claims 1 to 4 wherein the cyclodextrin is present in a composition which is soluble in aqueous media absorbed from a wound.

7. A wound dressing according to any preceding claim wherein the absorbent composition is in the form of a foam, an amorphous hydrogel, beads, granules, powder or a woven or non-woven pad.

8. A wound dressing according to claim 7 wherein the absorbent composition comprises a polyurethane or silicone foam.

9. A wound dressing according to claim 7 wherein the cyclodextrin is present in a hydrogel pad formed from a polyurethane or an acrylic polymer containing at least a proportion of hydrophilic monomer.

10. A wound dressing according to claim 7 wherein the absorbent composition comprises powder or granules composed of a mixture of pectin, gelatin and sodium carboxymethylcellulose, mixed with the cyclodextrin.

11. A wound dressing according to claim 7 wherein the absorbent composition comprises powder or granules composed of naturally occurring hydrocolloids, polyvinyl alcohol, polyoxyalkylene polyols and/or polyvinyl pyrrolidone, in conjunction with the cyclodextrin.

12. A wound dressing according to claim 7 wherein the cyclodextrin is present in an absorbent woven or non- woven pad composed of alginate, polyester, polyamide or polypropylene fibres.

13. A wound dressing according to claim 7 wherein the absorbent composition comprises dextranomer beads.

14. A wound dressing according to any preceding claim wherein the absorbent composition comprises one or more water-absorbable and/or water swellable hydrocolloids .

15. A wound dressing according to any preceding claim which includes an aqueous component which renders it capable of donating fluid to a wound.

16. A wound dressing according to claim 15 which includes a fragrance component complexed with the cyclodextrin.