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Title:
ANTIMICROBIAL MATERIAL
Document Type and Number:
WIPO Patent Application WO/2021/079126
Kind Code:
A1
Abstract:
A biocompatible material the method of making the same. The material comprises constituent fibres, yarns or filaments forming a woven, non-woven, gauze, film or knitted material incorporating an antimicrobial agent. The present material finds particular application as a wound dressing for the controlled and sustained release of a complexed form of iodine such as povidone-iodine or Cadexomer-iodine.

Inventors:
AGBOH CHRISTOPHER (GB)
FARRAR DAVID (GB)
Application Number:
PCT/GB2020/052664
Publication Date:
April 29, 2021
Filing Date:
October 22, 2020
Export Citation:
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Assignee:
IO CYTE LTD (GB)
International Classes:
A61L15/28; A61L15/42; A61L15/44; A61L15/60
Domestic Patent References:
WO2019012069A12019-01-17
WO2013140362A12013-09-26
WO2013078998A12013-06-06
Foreign References:
CN203576752U2014-05-07
EP0532275B11999-01-13
US20110171284A12011-07-14
US6897349B22005-05-24
US20140356454A12014-12-04
US20140239021A12014-08-28
Attorney, Agent or Firm:
NEILSON, Martin (GB)
Download PDF:
Claims:
Claims

1. A biocompatible material formed by a method of: providing a powdered iodine-complex; providing a fibre, yarn, filament or multifilament-based substrate having an open structure containing voids or interstitial regions; and introducing the powdered iodine-complex to the substrate to incorporate the iodine-complex within the structure of the substrate.

2. The material as claimed in claim 1 wherein the powdered iodine-complex comprises an iodophor, povidone-iodine, a starch-iodine-complex, a modified starch iodine-complex or the reaction product of dextrin, epichlorohydrin and iodine.

3. The material as claimed in claims 1 or 2 wherein the substrate is woven, non- woven, a gauze, a film or knitted.

4. The material as claimed in any preceding claim wherein the substrate comprises a water-absorbing swellable polymer.

5. The material as claimed in claim 4 wherein the material comprises any one or a combination of:

• a polysaccharide

• a polysaccharide-based material

• a hydrocolloid forming compound

• an alginate

• chitosan

• chitin

• pectin

• carboxymethyl cellulose

• hydroxypropyl methylcellulose

• gellan

• konjac; • psyllium.

6. The material as claimed in any one of claims 1 to 3 wherein the substrate comprises a polyester, a polyamide, a cellulosic, an acrylic or a biopolymer.

7. The material as claimed in any preceding claim further comprising a membrane provided over at least one external surface of the substrate, the membrane having an open structure to allow the iodine to be released from the material.

8. The material as claimed in claim 7 wherein the membrane is a gauze or mesh.

9. The material as claimed in claim 7 or 8 wherein the membrane encapsulates the substrate.

10. The material as claimed in any preceding claim wherein the substrate is a singular piece or comprises a layered structure.

11. The material as claimed in any preceding claim wherein the iodine-complex is adsorbed at a surface of the fibres, yarns, filaments or multifilaments of the substrate.

12. The material as claimed in any preceding claim further comprising a water- soluble control compound configured to control a release of the iodine from the material.

13. The material as claimed in claim 12 wherein the water-soluble control compound comprises a polyether, an alkyl ether, a glycol, a polyol or a compound having a C-O-C linkage.

14. The material as claimed in claim 12 wherein the water-soluble control compound comprises propylene glycol and/or polyethylene glycol.

15. The material as claimed in any preceding claim further comprising a polar organic compound comprising any one or a combination of an aldehyde, a ketone, an alcohol, an acetal or a compound with a hydroxyl group or a carbonyl group or acetone and/or isopropanol.

16. A biocompatible material comprising: a fibre, yam or filament-based substrate having an open structure containing voids or interstitial regions; and an iodine-complex releasably retained at the substrate and/or within the voids or interstitial regions.

17. The material as claimed in claim 16 wherein the iodine-complex is adsorbed at a surface of the fibres, yams, filaments or multifilaments of the substrate.

18. A method of forming a biocompatible antimicrobial material comprising: providing a powdered iodine-complex; providing a fibre, yarn, filament or multifilament-based substrate having an open structure containing voids or interstitial regions; and introducing the powdered iodine-complex to the substrate and allowing the powdered iodine-complex to be releasably retained at the substrate and/or within the voids or interstitial regions.

19. The method as claimed in claim 18 wherein the step of introducing the powered iodine-complex to the substrate comprises sonically agitating the substrate to facilitate entry of the iodine-complex into the voids.

20. The method as claimed in claims 18 or 19 further comprising prior to or after the step of introducing the iodine-complex to the substrate, applying an aqueous-based liquid to the substrate in which the iodine-complex is at least partially soluble.

21. The method as claimed in claim 20 wherein the aqueous liquid comprises any one or a combination of: water; a polar organic solvent; a water-soluble control compound configured to control a release of the iodine from the material.

22. The method as claimed in claim 21 wherein the aqueous liquid comprises an aldehyde, a ketone, an alcohol, an acetal or a compound with a hydroxyl group or a carbonyl group, acetone and/or isopropanol.

23. The method as claimed in claims 21 or 22 wherein the water-soluble control compound comprises any one or a combination of a polyether, an alkyl ether, a glycol, a polyol or a compound having a C-O-C linkage, propylene glycol and/or polyethylene glycol.

24. A wound dressing comprising the material as claimed in any one of claims 1 to 17.

25. The material as claimed in any one of claims 1 to 17 being any one of the following:

• a nasal packing material; or

• a dental packing material.

Description:
Antimicrobial Material

Field of the Invention

The present invention relates to a material incorporating an antimicrobial and a method of producing the same and in a particular, although not exclusively, to a woven, non-woven, gauze, film or knitted material incorporating an antimicrobial agent for use as a wound dressing.

Background Art

A variety of different dressings have been developed for treating many different types of wounds from grazes and cuts to more serious and problematic wounds such as burns or ulcers. In particular, these latter types of wound tend to produce significant quantities of exudate which more conventional pads and bandages cannot absorb.

Wound dressings may be formed from gauzes, films, woven or non-woven fabrics and swellable materials including hydrocolloids, alginates, hydrogels, polysaccharides. Such wound dressings may be natural or synthetic and are designed specifically for their biocompatibility.

For major wounds such as bums or ulcers it can be advantageous to prevent infection by introducing an antimicrobial agent to the wound. This may be applied directly before a fresh dressing is applied or more recently the antimicrobial may be incorporated into the dressing which is then placed directly onto the wound. The therapeutic and antimicrobial properties of iodine have been known for centuries with iodine-rich plants being used in the preparation of topical pastes to reduce pain and to help with wound healing. Iodophors are complexes of iodine and a solubilizing agent or carrier. The carrier also functions to control dissociation of the iodine to provide a sustained release when incorporated in a wound dressing and present on a wound in contact with wound exudate. A particular iodophor that has found more recent medical application is povidone-iodine (PVP-I) which is a complex salt of polyvinylpyrrolidone with triiodide ions. The antimicrobial activity of an iodophor, present within a wound dressing, is dependant on the amount of ‘free’ iodine, alternatively termed ‘ available ’ iodine that can be released into or onto the wound. This available iodine may be identified quantitatively via iodometry.

WO 2013/140362 A1 discloses a polymeric composite material having antimicrobial and biodegradable properties. The material is used to form medical devices having antiseptic action that is formed from a matrix of alginate and PVP-I. The composite material is used for producing films, micro-capsules and suture threads from which iodine may be released.

EP 0532275 B1 describes a wound dressing having an anhydrous water-soluble gel formed from a polysaccharide or cellulosic polymer together with a humectant. The dressing may also comprise a medicament or additive such as chlorohexidine, a silver compound or an antimicrobial such as PVP-I.

US 2011/0171284 A2 describes a medical dressing for wound healing including a sucrose, PVP-I and a gelling agent sufficient to thicken the composition to control release of sucrose and iodine to the wound. WO 2013/078998 A1 describes a slow-release ophthalmic composition containing PVP-I to treat acute ophthalmic infections. The composition includes a pharmaceutically acceptable excipient (e.g. water) and PVP-I formed in microspheres with sodium alginate.

US 6,897,349 B2 describes methods and compositions for making a silver-containing antimicrobial hydrophilic material suited for use as wound dressings to control and manage extrudate drainage.

US 2014/0356454 A1 describes an antimicrobial wound dressing derived from gel-forming fibres such as cellulose or alginate fibres having silver ions uniformly incorporated amongst the matrix.

However, antimicrobial wound dressings are required offering enhanced exudate management and sustained and controlled release of the pharmaceutically active agent.

Summary of Invention

It is an objective of the present invention to provide a pharmaceutically active material suitable as a wound dressing exhibiting moisture absorbing characteristics whilst providing a sustained and controlled release of the antimicrobial agent. It is a further objective to provide a woven, non-woven, gauze, film or knitted material having desired physical and mechanical characteristics for the treatment of a variety of different types of wound including minor cuts and grazes to more serious forms such as bums and ulcers.

The objectives are achieved by providing a woven, non-woven, gauze, film or knitted material that may in turn be formed from fibres, yarns, and/or filaments that provides a controlled and sustained release of iodine as an antimicrobial agent. In particular, the present material when positioned at a wound is effective to achieve a desired moisture vapour transmission rate from the wound and through the material and a desired physical integrity so as not to degrade when in contact or absorbing moisture and exudate. Additionally, the present material if absorbent may be configured for moisture retention so as to provide a hygroscopic humectant whilst also enabling convenient release or decoupling from the wound when required.

According to a first aspect of the present invention there is provided a biocompatible material formed by a method of: providing a powdered iodine-complex; providing a fibre, yarn, filament or multifilament-based substrate having an open structure containing voids or interstitial regions; and introducing the powdered iodine-complex to the substrate to incorporate the iodine-complex within the structure of the substrate.

The present materials and processes may be configured specifically for the controlled and sustained antimicrobial release at the wound as well as having a desired moisture vapour transmission rate (MVTR), physical integrity - so as not to degrade when exposed to exudate.

The present materials and methods may utilise a variety of different water-soluble polymers including natural or synthetic materials. Such water-soluble polymers are moisture absorbing swellable polymers and include for example polysaccharides or polysaccharide-based materials, hydrocolloids, biopolymers. A preferred form of water- soluble polymer is a polysaccharide alginate.

The present fibre and methods may utilise additional compounds to further control the release of iodine from the fibre. Such additional components may include a secondary water-soluble control compound such as a polyether, an alkyl ether, a glycol such as propylene glycol (PG), a polyol or a compound having a C-O-C linkage such as polypropylene glycol (PPG) or polyethylene glycol (PEG). In particular, it is preferred that the water-soluble control compound is polar or at least partially polar. It is hypothesised that the water-soluble control compound may interact via electrostatics and/or structural conformation so as to at least partially inhibit disassociation of the iodine from its complexed form. Accordingly, the iodine is inhibited from uncontrolled or free release from the material by interaction of the iodine and/or the iodine-complex with the water-soluble control compound. Optionally, the powdered iodine-complex comprises an iodophor, povidone-iodine, a starch-iodine-complex, a modified starch iodine-complex or the reaction product of dextrin, epichlorohydrin and iodine.

The powdered iodine-complex may be in powdered form when initially introduced to the substrate and may be solvated or at least partially solvated when positioned at the substrate via a moistening liquid applied to the biocompatible substrate material prior to or after addition of the powered iodine-complex. Such moistening of the substrate is effective to firstly adhere the iodine-complex to the fibres, yams or filaments of the substrate and also to provide at least some absorption of the iodine into the body of the fibres, yams or filaments. Optionally, the powdered iodine-complex is added to the substrate so as to enter and be releasably retained within the voids or interstitial regions of the material. Such voids or inner regions may include the micron-sized interstitial zones between the fibres, yarns, filaments or body of the material matrix.

Importantly, the present fibre and material, once manufactured, comprises a desired moisture content due to the specific step of adding a moistening liquid to the material.

This moistening liquid may be aqueous-based or organic-based. Optionally, the moistening liquid may comprise both an aqueous-based and an organic-based component at different concentrations. In particular, the organic moistening component may be included within the material at a greater concentration than the aqueous-based moistening liquid. A material having a desired moisture content facilitates use as a wound dressing for placement onto a wound and to achieve the desired physical and mechanical characteristics such as the desired moisture vapour transmission rate, exudate absorption etc. Optionally, the present fibre and material comprises a moisture content in the range 5 to 60%, 10 to 60%, 15 to 55%, 20 to 50%, 25 to 50%, 30 to 50%, 30 to 45% or 35 to 40% moisture. The moisture content may be determined by any suitable method. For example, the moisture content may be determined by subtracting the dry weight of the fibre or material from the appropriately moistened fibre or material and then dividing this difference (moisture content) by the total weight of fully moistened fibre/material. The values of moisture content reported herein therefore are relative moisture wt% ranges of the amount of moistening liquid within the moistened material. The present fibre and material may comprise a moistening liquid being any one or a combination of water, a water-based solution, an organic liquid, an organic solution, acetone, isopropanol.

Optionally, the substrate maybe woven, non-woven, a gauze, a film or knitted.

Importantly, the substrate may be formed as a matrix having an internal ‘open’ structure formed from voids, cavities or regions into which the complex-iodine maybe introduced and be at least partially retained. Further, the complex-iodine is adsorbed to the body of the matrix to provide controlled and sustained release.

Optionally, the substrate comprises a water-absorbing swellable polymer. Optionally, the swellable polymer may comprise any one or a combination of a polysaccharide; a polysaccharide based material; a hydrocolloid forming compound; an alginate; chitosan; chitin; pectin; carboxymethyl cellulose; hydroxypropyl methylcellulose; gellan; konjac; or psyllium.

Optionally, the substrate may comprise a synthetic polymer such as polyester, a polyamide, a cellulosic, an acrylic or a biopolymer.

Optionally, the material may further comprise a membrane provided over at least one external surface of the substrate, the membrane having an open structure to allow the iodine to be released from the material. Optionally, the membrane maybe a gauze, mesh, layer, a woven or non-woven material. A density of the material of the encapsulating layer(s) maybe less than, approximately equal to or greater than a density of the material that represents a majority component of the substrate. Reference within this specification to a majority component encompasses a material, fibre, yarn, strand or filament being the largest wt% compositional component of the entire structure. Preferably, the membrane encapsulates partially or fully the substrate incorporating the complexed-iodine.

Optionally, the substrate maybe a singular piece or comprises a layered structure. As a result of the moistening step as described herein, the present material does not comprise or require an outer membrane (optionally implemented as a gauze or mesh) to retain the iodine-complex. In particular, the moistening step is advantageous to bind the iodine-complex to the fibre strands of the material. The present outer membrane-free material is configured for direct positioning against a wound and is advantageous for ease of manufacture whilst also providing a more effective wound dressing for direct transfer and release of the iodine-complex to the wound region.

The polymer substrate as described herein, is swellable but is not soluble in the moistening liquid as described herein.

Optionally, the iodine-complex is adsorbed at a surface of the fibres, yams, filaments or multifilaments of the substrate. Preferably, the iodine-complex is at least partially absorbed at the fibres, yarns, filaments or multifilaments of the substrate.

Optionally, the material may further comprise a water-soluble control compound configured to control a release of the iodine from the material. Optionally, the water- soluble control compound comprises a polyether, an alkyl ether, a glycol, a polyol or a compound having a C-O-C linkage. More preferably, the polymer comprises propylene glycol and/or polyethylene glycol.

Optionally, the material and/or the aqueous liquid may further comprise a polar organic compound comprising any one or a combination of an aldehyde, a ketone, an alcohol, an acetal or a compound with a hydroxyl group or a carbonyl group or acetone and/or isopropanol.

According to a further aspect of the present invention that is provided a biocompatible material comprising: a fibre, yam or filament-based substrate having an open structure containing voids or interstitial regions; and an iodine-complex releasably retained at the substrate and/or within the voids or interstitial regions. The iodine-complex may be absorbed into the fibre, yam or filaments and/or may be present at the surface(s) of the fibre, yarn or filaments. Optionally, at least some of the iodine-complex may be considered to be accommodated within the interstitial regions of the material matrix structure. It is hypothesised that the iodine-complex at these interstitial voids may be held in-position and/or be releasably retained by relatively weak electrostatic interaction with the substrate and/or by adsorption and relatively weak chemical association with the material yarn, fibres, filaments or body.

According to a further aspect of the present invention there is provided a method of forming a biocompatible antimicrobial material comprising: providing a powdered iodine- complex; providing a fibre, yarn, filament or multifilament-based substrate having an open structure containing voids or interstitial regions; and introducing a powdered iodine- complex to the substrate and allowing the powdered iodine-complex to be releasably retained at the substrate and/or within the voids or interstitial regions.

Optionally, the step of introducing the powered iodine-complex to the substrate comprises sonically agitating the substrate to facilitate entry of the iodine-complex into the voids. Optionally, the method further comprises prior to or after the step of introducing the iodine-complex to the substrate, applying an aqueous-based liquid to the substrate in which the iodine-complex is at least partially soluble.

Optionally, the aqueous liquid comprises any one or a combination of water; a polar organic solvent; a water-soluble control compound configured to control a release of the iodine from the material.

According to a further aspect, the present method comprises adding a powdered iodine complex to a substrate, moistening the substrate either pre or post addition of the powdered iodine complex, and allowing the moistened substrate to dry or at least partially dry. Preferably, the method further comprises compressing, squeezing or pressing the moistened substrate to expel excess moisture prior to allowing the moistened substrate to dry. Compressing or pressing the moistened substrate is advantageous to drive impregnation of the fibres with the iodine complex. Additionally, this step facilitates uniform distribution of the iodine complex over the surface of the fibres and optionally into the core or inner region of the fibre body.

According to a further aspect of the present invention there is provided a wound dressing comprising the material as claimed herein.

According to a further aspect of the present invention there is provided a material as described and claimed herein being any one of: a nasal packing material; or a dental packing material. Optionally the present material when used as a wound dressing or packing material is non-woven.

Brief description of drawings

A specific implementation of the present subject matter will now be described, by way of example only, and with reference to the accompanying drawings in which:

Figure l is a schematic illustration of an iodine-complex incorporated within a fibrous wound dressing material according to a specific implementation of the present invention;

Figure 2 is a schematic illustration of an iodine-complex incorporated within a fibrous wound dressing material having an outer iodine-containment layer, sheet or mesh according to a further specific implementation of the present invention;

Figure 3 is a schematic illustration of an iodine-complex incorporated within a fibrous wound dressing material having an alternative outer iodine-containment layer, according to a further specific implementation of the present invention.

Detailed description

The present antimicrobial material may be formed from a non-woven felt-like material, a woven or knitted material that, in turn, may be utilised as a wound dressing for the treatment of a variety of different types of wound from cuts and grazes to more serious burns, ulcers and the like where exudate management is critical. The present material is conveniently formed from the introduction of a powdered and complexed form of iodine to a suitable substrate. The substrate material may be dry as the complexed form of iodine is dispensed on to and into it. In certain embodiments, the substrate containing the complexed iodine may then be moistened using a suitable solvent system to facilitate adhesion of the iodine at the substrate and inhibit undesirable leaching or premature/uncontrolled release. In certain alternative embodiments, the substrate may be pre-moistened using a suitable solvent system in order to achieve the same or a similar level of iodine retention/capture.

In certain embodiments, the substrate may be formed from fibres, sliver, roving, single or multifilaments or yarn. The substrate may be a swellable (optionally a humectant) or non- swellable material. The present materials incorporate ‘ available ’ iodine within the matrix of the material and in particular within the voids and cavities between the strands, yarn or fibres of the material. In certain embodiments, at least some of the complexed iodine may be present within the body of the constituent fibres, yams or filaments. In certain embodiments, at least some of the complexed iodine may be present the surface of at the fibre/yarn surface constituent fibres, yarns or filaments.

The iodine is in a form of an iodine-complex and included at a concentration level sufficient to provide antimicrobial activity. Such concentration levels may be of the order of greater than 1 wt% ‘free’ iodine within a total weight of material. The present materials and processes are specifically designed to provide a material having a desired moisture vapour transmission rate (MVTR), physical integrity - so as not to degrade when exposed to exudate and in a moisture absorbed swollen configuration, in addition to providing controlled and sustained antimicrobial release at the wound.

The present materials and methods may utilise a variety of different water-soluble or non water soluble polymers including natural or synthetic materials. In certain embodiments, the material, suitable for use as a wound dressing, may comprise at least one water-soluble polymer that is a moisture absorbing swellable polymer and include for example polysaccharides or polysaccharide based materials, hydrocolloids, biopolymers. A preferred form of water-soluble polymer is a polysaccharide alginate.

The present examples describe procedures developed to incorporate complexed-iodine into alginate and similar biomaterials in various forms such as fibres, sliver, roving, non- woven, woven or knitted.

The present materials may be formed from a polymer having the complexed iodine (for example PVP-I) absorbed within the fibres/yarns/filaments and also the complexed iodine adsorbed at the fibre surfaces. This dual presence of the complexed iodine provides at least two mechanisms of release. For example, the complexed iodine adsorbed at the surfaces of the constituent yarns, fibres, filaments may be released quickly and/or immediately as the wound dressing is brought into contact with the wound. In addition, the complexed iodine absorbed (incorporated at the fibre/yarn/filament body) may be adapted for slower more sustained release over time.

In certain embodiments, the complexed iodine is povidone-iodine (PVP-I) which is a well- known antimicrobial agent with a broad spectrum of antimicrobial activity. PVPI is a complex of polyvinylpyrrolidone (povidone, PVP) and elemental iodine. The PVP solubilises the iodine and releases it in a controlled way thus reducing the toxicity to mammalian cells compared to solutions of iodine such as LugoTs solution (iodine and potassium iodide in water). For example, Inadine™ (Systagenix) consists of a low adherent knitted viscose fabric impregnated with 10% povidone Iodine that is equivalent to 1.0% available ‘free’ iodine. In certain embodiments, the present material may comprise an alternative complexed form of iodine such as Cadexomer-iodine which is a water-soluble modified starch containing 0.9% w/w iodine. Cadexomer-iodine is available in paste dressing, powder, ointment/gel forms e.g. Iodoflex™ and Iodosorb™ (Smith & Nephew).

The present materials and methods may utilise additional compounds to further control the release of iodine from the material. Such additional components may include secondary control compounds such as polyethers, alkyl ethers, glycols such as propylene glycol (PG), polyolsor a compound having a C-O-C linkage such as polypropylene glycol (PPG) or polyethylene glycol (PEG). The water-soluble control compound also present within the fibres/yarn/filaments of the material provides further control of the release of ‘free’ iodine to promote a sustained release.

Example 1

Incorporation ofPVPIin substrate by spraying

The present example describes attempts made to incorporate BASF PVPI 30/06 powder into biomaterials such as alginate fibres or felt by spraying and in particular by spraying a substrate with powdered (dry) PVPI.

Initial attempts at spraying powdered PVPI on dry non-woven felts and fibres failed notwithstanding the compactness of the fibres and the non-woven structures. Most of the samples treated had brown-yellow colour (due to incorporation of PVPI) and the depth of colour appeared to deepen by gently rubbing the powder into the fibre structure. However, there were too many loose powder particles in the structures, and these were released readily as soon as the materials were lifted and /or shaken.

In a set of further attempts, the PVPI powder was dispensed/sprayed on to dampened or moistened non-woven felts or fibres. The PVPI powder was poured into a powder sprayer adapted to dispense powdered materials with consistent qualities and concentrations. A suitable device is disclosed in US 2014/239021 Al, the contents of which as relating specifically to the powder dispenser as incorporated herein by reference. Such a dispenser comprises a container defining a cavity for storing the material and a pump body positionable in the cavity having a pump chamber, a pickup chamber, and a dispensation chamber.

The PVPI powder was dispensed/sprayed on to the dampened or moistened non-woven felts or fibres to various depths of colour. The moist PVPI containing substrates where then hanged to dry overnight. A variety of common, non-toxic solvents were used to moisten the substrate, prior to powder spraying. These were tried alone and in combinations as indicated in table 1. Table 1: Application of PVPI on non-woven felt through spraying An iodine-containing powder incorporated into a fibrous wound dressing material is illustrated in Figure 1. The non-woven material is formed from polysaccharide fibres 10 and comprises an open structure having voids or cavities 12 within the body of the material. The complexed-iodine in the form of PVPI 11 is disbursed homogeneously within the fibrous polysaccharide 10 and in particular is located within the internal voids 12. As indicated, the complexed-iodine 11 may optionally comprise Cadexomer-iodine in powdered form.

According to further variations of example 1, the PVPI can be introduced and encourage to penetrate deep into the matrix (between the fibre, yams, filaments of the material) by sonic agitation of the substrate after the powdered PVPI has been applied and prior to substrate moistening.

Example 2

PVPI sprayed into dry substrates followed by moistening

In this example, the complex iodine, (e.g. PVPI) was introduced to a dry substrate in the form of the fibrous polysaccharide wound dressing of example 1. The material may be agitated optionally by sonic agitation to distribute homogeneously the complexed-iodine amongst the polysaccharide fibres. The material incorporating the PVPI was then moistened with any one or a combination of the moistening liquids as detailed in table 1.

The effect of moistening the substrate and PVPI in combination (post-powder spraying of the PVPI onto the substrate) was to at least partially solvate the PVPI and also to moisten the fibres. Firstly, an amount of the PVPI was capable of absorbing into the body of the fibres. Additionally, wetting the fibres also facilitated adsorption of the PVPI to the fibrous surfaces. Accordingly, moistening was effective to adhere the PVPI to the non- woven substrate that in turn provides controlled and sustained release of the ‘free’ iodine in use.

Example 3

Retention of PVPI into substrates by porous layer(s) or mesh

A non-woven polysaccharide 10 incorporating PVPI 11 within the voids 12 of the polysaccharide matrix according to example 1 or 2 was prepared. However, in a first variation of example 3, the substrate was not moistened prior to or following introduction of the PVPI. Instead, the PVPI 11 was locked-in to the material matrix via first and second porous sheets or mesh 13a, 13b positioned to at least partially cover or encapsulate the polysaccharide 11 and PVPI 11 as detailed referring to figure 2. The porous sheet or mesh 13a, 13b is formed as layers having a porosity suitable to allow release of the PVPI 11 from the polysaccharide substrate 10 and onto a wound positioned adjacent at least one of the layers 13a, 13b. As a further variation of example 3, the substrate 10 and PVPI 11 may be moistened with any one of the moistening liquids of table 1 pre or post introduction of the PVPI 11 into the voids 12.

Example 4

Retention of PVPI into substrates by porous non-woven polymer layer(s)

According to Figure 3, a non-woven polysaccharide 10 incorporating PVPI 11 within the voids 12 was prepared according to example 3 in which the material was not moistened or was moistened pre or post addition of PVPI 11 into the voids 12. The composite structure 10, 11 was at least partially encapsulated or covered by layers 14a, 14b of a non-woven polysaccharide being denser than the polysaccharide 10 that forms the majority component of the substrate having internal voids 12 within its matrix. The density of the non-woven layers 14a, 14b may be selected to achieve the desired release rate of PVPI onto the wound. As will be appreciated, the density of layers 14a, 14b will affect directly the transmission/diffusion of the PVPI 11 through the fibres of the layers 14a, 14b.

In specific embodiments, the majority of non-woven polysaccharide substrate 10 may be moistened prior to addition of the encapsulating layers 14a, 14b. In particular, it may be advantageous to allow the substrate 10 to dry before covering with layers 14a, 14b.

From the investigation, some of the conclusions reached included:

• The technique can be successfully used to incorporate PVPI into biomaterials.

• The retention of a complexed form of iodine into a substrate may be achieved by any one or a combination of:

• moistening the substrate

• at least partially encapsulating, coating or covering the substrate with a suitable outer retaining membrane or layer such as an open fabric, non-woven, woven, gauze, mesh or layer.

• incorporating into the substrate a suitable polymer to inhibit the leaching-out or loss of iodine in use. Such a polymer may include PEG, PG or the like. • it appeared that volatile liquids alone or containing very small amount of water (<10%) produced samples with good depth of colour, uniformity, flexibility, absorbency and rubbing fastness. Unless defined otherwise all technical and scientific terms used herein have the same meaning as commonly understood to one of ordinary skill in the art to which the presently described subject matter pertains.

Where a range of values is provided, for example, concentration ranges, percentage ranges, or ratio ranges, it is understood that each intervening value, to the tenth of the unit of the lower limit, unless the context clearly dictates otherwise, between the upper and lower limit of that range and any other stated or intervening value in that stated range, is encompassed within the described subject matter. The upper and lower limits of these smaller ranges may independently be included in the smaller ranges, and such embodiments are also encompassed within the described subject matter, subject to any specifically excluded limit in the stated range. Where the stated range includes one or both of the limits, ranges excluding either or both of those included limits are also included in the described subject matter.