[go: up one dir, main page]

WO2016146972A1 - Matériau antimicrobien - Google Patents

Matériau antimicrobien Download PDF

Info

Publication number
WO2016146972A1
WO2016146972A1 PCT/GB2016/050658 GB2016050658W WO2016146972A1 WO 2016146972 A1 WO2016146972 A1 WO 2016146972A1 GB 2016050658 W GB2016050658 W GB 2016050658W WO 2016146972 A1 WO2016146972 A1 WO 2016146972A1
Authority
WO
WIPO (PCT)
Prior art keywords
poly
iodine
clay
layer
polymer
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
Application number
PCT/GB2016/050658
Other languages
English (en)
Inventor
Christopher Breen
Neil BRICKLEBANK
Francis Clegg
Louise FREEMAN-PARRY
Marianne LABET-EYLEY
Keith Miller
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Sheffield Hallam University
Original Assignee
Sheffield Hallam University
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Sheffield Hallam University filed Critical Sheffield Hallam University
Publication of WO2016146972A1 publication Critical patent/WO2016146972A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L15/00—Chemical aspects of, or use of materials for, bandages, dressings or absorbent pads
    • A61L15/16—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons
    • A61L15/18—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons containing inorganic materials
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N25/00—Biocides, pest repellants or attractants, or plant growth regulators, characterised by their forms, or by their non-active ingredients or by their methods of application, e.g. seed treatment or sequential application; Substances for reducing the noxious effect of the active ingredients to organisms other than pests
    • A01N25/08—Biocides, pest repellants or attractants, or plant growth regulators, characterised by their forms, or by their non-active ingredients or by their methods of application, e.g. seed treatment or sequential application; Substances for reducing the noxious effect of the active ingredients to organisms other than pests containing solids as carriers or diluents
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N31/00—Biocides, pest repellants or attractants, or plant growth regulators containing organic oxygen or sulfur compounds
    • A01N31/04—Oxygen or sulfur attached to an aliphatic side-chain of a carbocyclic ring system
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
    • A01N43/34—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one nitrogen atom as the only ring hetero atom
    • A01N43/36—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one nitrogen atom as the only ring hetero atom five-membered rings
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N59/00—Biocides, pest repellants or attractants, or plant growth regulators containing elements or inorganic compounds
    • A01N59/08—Alkali metal chlorides; Alkaline earth metal chlorides
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N59/00—Biocides, pest repellants or attractants, or plant growth regulators containing elements or inorganic compounds
    • A01N59/12—Iodine, e.g. iodophors; Compounds thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F13/00—Bandages or dressings; Absorbent pads
    • A61F13/01—Non-adhesive bandages or dressings
    • A61F13/01008—Non-adhesive bandages or dressings characterised by the material
    • A61F13/01017—Non-adhesive bandages or dressings characterised by the material synthetic, e.g. polymer based
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K33/00—Medicinal preparations containing inorganic active ingredients
    • A61K33/18—Iodine; Compounds thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/70—Web, sheet or filament bases ; Films; Fibres of the matrix type containing drug
    • A61K9/7007—Drug-containing films, membranes or sheets
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L15/00—Chemical aspects of, or use of materials for, bandages, dressings or absorbent pads
    • A61L15/16—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons
    • A61L15/22—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons containing macromolecular materials
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08K—Use of inorganic or non-macromolecular organic substances as compounding ingredients
    • C08K3/00—Use of inorganic substances as compounding ingredients
    • C08K3/02—Elements
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08K—Use of inorganic or non-macromolecular organic substances as compounding ingredients
    • C08K3/00—Use of inorganic substances as compounding ingredients
    • C08K3/18—Oxygen-containing compounds, e.g. metal carbonyls
    • C08K3/20—Oxides; Hydroxides
    • C08K3/22—Oxides; Hydroxides of metals
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08K—Use of inorganic or non-macromolecular organic substances as compounding ingredients
    • C08K3/00—Use of inorganic substances as compounding ingredients
    • C08K3/34—Silicon-containing compounds
    • C08K3/346—Clay
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08L—COMPOSITIONS OF MACROMOLECULAR COMPOUNDS
    • C08L29/00—Compositions of homopolymers or copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and at least one being terminated by an alcohol, ether, aldehydo, ketonic, acetal or ketal radical; Compositions of hydrolysed polymers of esters of unsaturated alcohols with saturated carboxylic acids; Compositions of derivatives of such polymers
    • C08L29/02—Homopolymers or copolymers of unsaturated alcohols
    • C08L29/04—Polyvinyl alcohol; Partially hydrolysed homopolymers or copolymers of esters of unsaturated alcohols with saturated carboxylic acids
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08L—COMPOSITIONS OF MACROMOLECULAR COMPOUNDS
    • C08L39/00—Compositions of homopolymers or copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and at least one being terminated by a single or double bond to nitrogen or by a heterocyclic ring containing nitrogen; Compositions of derivatives of such polymers
    • C08L39/04—Homopolymers or copolymers of monomers containing heterocyclic rings having nitrogen as ring member
    • C08L39/06—Homopolymers or copolymers of N-vinyl-pyrrolidones
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08L—COMPOSITIONS OF MACROMOLECULAR COMPOUNDS
    • C08L39/00—Compositions of homopolymers or copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and at least one being terminated by a single or double bond to nitrogen or by a heterocyclic ring containing nitrogen; Compositions of derivatives of such polymers
    • C08L39/04—Homopolymers or copolymers of monomers containing heterocyclic rings having nitrogen as ring member
    • C08L39/08—Homopolymers or copolymers of vinyl-pyridine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/10—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing inorganic materials
    • A61L2300/106—Halogens or compounds thereof, e.g. iodine, chlorite

Definitions

  • the present invention relates to an antimierobial composite material containing a clay for use in, but not limited to, wound dressings.
  • Wound infections are a common healthcare problem and can lead to significant mortality and morbidity.
  • a wound is a breach in the epidermis or dermis due to trauma or physiological change which activates the repair process.
  • Wounds can be divided into two main categories, acute or chronic. Acute wounds heal within a predictable time frame, whereas wounds that fail to heal within six weeks of the initial injury are described as chronic and often have prolonged pathological inflammation.
  • Chronic wounds usually occur because of an underlying pathophysiological abnormality leading to poor tissue perfusion.
  • the most common chronic wounds include venous leg ulcers, diabetic foot ulcers and pressure sores (decubitus ulcers) which account for over 70% of chronic wounds in the UK.
  • Chronic wounds involve extensive tissue damage, due to the exposed subcutaneous tissue providing a moist, warm and nutritious environment for a wide variety of microorganisms to colonise. Wound infection occurs when pathogenic microorganisms evade the host's immunological defences and multiply causing a host reaction.
  • Infection produces localised pain and swelling, spreading erythema, production of purulent exudates, odour and the presence of a positive bacterial culture with more than 10 6 colony- forming units per mm 3 tissue.
  • topical antiseptics/ antimicrobials are recommended.
  • the aim of treatment is to remove infection from surrounding tissue and reduce the wound bioburden. If untreated, pathogenic bacteria can produce toxins which destroy local tissue and once established in the deeper tissues they continue to multiply and enter the circulation causing bacteraemia.
  • the effects of wound infection can range from delayed healing, causing disability and hospital admission, to life- threatening septicaemia, sometimes leading to death.
  • a topical antimicrobial agent which could be either a cream, ointment or impregnated wound dressing.
  • a topical antimicrobial agent which could be either a cream, ointment or impregnated wound dressing.
  • a number of different materials have been used in the manufacture of wound dressings.
  • antimicrobial agents such as silver is expensive and do not always target a broad spectrum of bacteria.
  • WO2013028214 A further problem with silver based antimicrobial materials is the increased resistance by a growing number of strains of bacteria to the effects of the antimicrobial agent.
  • a further problem with some existing wound dressings is that their low moisture absorbency makes them ineffective at taking-in the large amounts of wound exudate produced and promote healing. Moreover, it can be difficult for healthcare professionals to determine whether the antimicrobial agent in the dressing has been consumed and if replacement of the dressing is required.
  • a significant problem associated with existing antimicrobial materials is the ineffective sustained delivery of the antimicrobial agent to the wound over an extended period of typically several days.
  • the relatively rapid release rate of the entire microbial dose from existing materials causes time management problems for healthcare professionals who must ensure that wound dressings are changed regularly so as to provide an effective and sustained antimicrobial treatment.
  • an antimicrobial material for use as a surface coating at a substrate to impart antimicrobial properties to the substrate. It is a further objective of the present invention to provide an antimicrobial material that may be regarded as free-standing or self-supporting or a material that may be layered or backed by additional materials.
  • the objectives are achieved by providing an iodine based antimicrobial material in which the iodine is complexed within the materia! but may be released particularly when the material is exposed to moisture such as wound exudate and the like.
  • Iodine is
  • iodine penetrates microorganisms and attacks their key proteins, nucleic acids and fatty acids leading to cell death.
  • Aqueous solutions of iodine are unstable and at least seven iodine species exist including: I 2 , HOI, 10 " , H 2 OI + , I 3 " , ⁇ and IO3 " .
  • I2 hydrated iodine
  • HOI hypoiodous acid
  • H 2 QI + iodine cation
  • the pH of the solution influences the dynamic equilibrium and the relative proportions of the different iodine containing moieties and maximum antimicrobial activity occurs when the forms of iodine without antimicrobial activity are minimised.
  • the subject invention may include iodine in the form of iodophors e.g poly( inyl pyrrolidone)-iodine and poloxymer-iodine by complexing iodine and a solubilising agent or carrier which acts as a reservoir of the active 'free' iodine.
  • the iodine is made less toxic by incorporation with agents such as poly( vinyl pyrrolidone) iodine (PVP-I2) complexes which make it more soluble and less allergenic.
  • PVP-I2 poly( vinyl pyrrolidone) iodine
  • Poly( vinyl pyrrolidone) iodine acts as a reservoir which slowly releases active iodine from its complex bound form. As the iodine is rendered inactive following the destruction of microorganisms further iodine is released, maintaining an equilibrium until the reservoir is empty.
  • an antimicrobial composite material comprising: a heteroatom containing first polymer complexed to iodine or an iodine-containing species; a second polymer to promote formation of the material; and a clay.
  • the antimicrobial material comprises a second part such as poly(vinyl alcohol) (PVOH) to facilitate robust film formation of the material and preferably self- stratification.
  • the material further comprises a clay specifically in the form of clay platelets that provide a dual function. Firstly, the clay helps to compatibilize the first polymer and the second polymer within the material and secondly the clay may act to increase the tortuosity of the path that iodine (and other molecules) must travel to progress through and exit the material. This second characteristic may provide a contribution to the controlled release of the iodine.
  • Clay is a common name for a number of natural or synthetic fibrous or layered minerals and examples suitable for use with the subject invention include, but are not limited to kaolin, halloysite, talc, smectite, hectorite, saponite, vermiculite, mica, attapulgite and sepiolite.
  • the present material may comprise bentonite which is an impure 2:1 layered phyllosilicate whose main composition consists of montmorillonite where montmorillonite is a layered clay mineral of the smectite group with an aluminosilicate structure having a hydrophilic character.
  • the single clay or clay combinations used in the present material have ion exchange capacities and may belong to the bentonite type of clays, in which the main constituents are sodium montmorillonite and calcium montmorillonite and blends thereof.
  • the present material comprises multivalent- or inorganic cation-exchanged grades and organic cation-exchanged clays and/or other clays which can be purified and suitably ion exchanged.
  • the material comprises a first clay of a first type and a second clay of a second type or a first and second clay of the same type wherein the first and second clays are saturated respectively with different exchange cations.
  • the clay is distributed within the material in the form of discrete platelets or assemblies (stacks) of a small number of platelets to control a release of the iodine from the material.
  • Reference within this specification to 'a heteroatom containing first polymer ' refers to a polymer comprising predominantly carbon and having non-carbon atoms within the polymer structure and in particular the polymer backbone or side chains.
  • the heteroatoms may comprise nitrogen, oxygen, sulphur, phosphorus, chlorine, bromine and/or iodine.
  • This term also encompasses organic based polymers including aliphatic, aromatic, conjugated and non-conjugated polymer species which have such heteroatoms.
  • This term also encompasses biological compounds including naturally occurring compounds such as proteins and the like and synthetic polymers incorporating heteroatoms.
  • examples include but are not limited to, poly(alkylacetate), poly(alkylalcohol), poly(ethylalcohol), poly(vinylacetate), poly(vinylalcohol), poly(ethylvinylalcohol), polyamide, poly(aniline), poly(acrylonitrile), poly(pyrrole), poly(N-vinylcarbazole), poly(N-vinylimidazole), poly(2- vinylpyridine-co-styrene-co- divinylbenzene), poly(acetylene), starch, chitosan, cellulose and polyvinylpyrrolidone) (PVP).
  • PVP polyvinylpyrrolidone
  • the material is organised into a plurality of layers.
  • the material is organised into a first layer and a second layer.
  • the first layer is lighter coloured and comprises a higher concentration of clay than the second darker layer which comprises a lower concentration of clay than the first layer.
  • the first layer is configured to produce a larger zone of inhibition against the bacterial species than the second layer.
  • the first layer may be placed in contact with the wound to produce a fast- acting, quick-release of iodine to the infected area.
  • the second layer with a lower concentration of clay may be placed in contact with the wound to produce a sustained iodine release.
  • the first layer containing the higher concentration of clay may provide the sustained iodine release whilst the second layer with a lower concentration of clay may provide the fast-acting, quick-release of iodine.
  • the first layer in combination with the second layer has the ability to draw water to the top of the material when the second layer is placed in contact with a wound.
  • This phenomenon is referred to as 'wicking' in the wound care technology field and is advantageous for treating wounds with excess exudate.
  • first polymer and the second polymer may comprise the same material species but differ in that the second polymer is not complexed to iodine or an iodine- containing species.
  • first and second polymers comprise
  • the second polymer comprises any one or a combination of the set of polymers; examples of which include but are not limited to, poly(alkylaceiate).
  • the second polymer comprises polyvinyl alcohol (PVOH).
  • the clay comprises any one or a combination of the following set of: kaolin, halloysite, talc, montmorillonite, bentonite, hectorite, saponite, vermiculite, mica, attapulgite and sepiolite.
  • the clay comprises a bentonite clay formed from Sodium bentonite and or multivalent cation-exchanged bentonite.
  • the bentonite clay consists essentially of Sodium Bentonite and/or Calcium Bentonite.
  • the bentonite clay comprises montmorillonite clay.
  • the clay comprises CloisiteTM Na + .
  • a concentration of the iodine within the material is in the range 0.1 to 15 wt%, Such a concentration at the upper end of the range is advantageous to avoid damage to a patient due to toxicity affects associated with higher concentrations of iodine.
  • a wound dressing comprising the antimicrobial composite material as claimed herein.
  • the wound dressing comprises a backing material (layer) and optionally an adhesive backing attached to the composite material.
  • a substrate comprising a surface coating comprising the antimicrobial composite material as claimed herein.
  • a method of manufacturing an antimicrobial composite material comprising: creating a slurry by mixing a heteroatom containing first polymer complexed to iodine or an iodine-containing species, a second polymer and a clay in a solvent; and drying the slurry to form the composite material.
  • the solvent may be an aqueous medium or an organic solvent including single and multiple/mixed solvent systems.
  • the solvent may be selected to facilitate drying of the slurry and in particular a volatile solvent system may be advantageous to reduce a drying time during manufacture.
  • Figure 1 is a schematic illustration of an antimicrobial material containing an antimicrobial agent distributed within a clay-polymer matrix, where the arrows show the indirect release paths of the antimicrobial agents;
  • Figure 2 is a schematic perspective view of an antimicrobial material comprising a first layer and a second layer;
  • Figure 3 is a plan view of a sample antimicrobial material within a petri-dish where the arrows indicate the orthogonal diameters of the zone of inhibition;
  • Figure 4 is a graph of the clay/polymer composition for selected examples of antimicrobial materials
  • Figure 5 is a graph of the average zone of inhibition versus available iodine to show the influence of the antimicrobial concentration on the zone of inhibition for the bacteria Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa',
  • Figure 6 is a graph of a duration of antimicrobial activity as determined from the size of the zone of inhibition over 192 hours for a selection of microbes including Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa;
  • Figure 7 is a further graph of a duration of antimicrobial activity as determined from the size of the zone of inhibition over 144 hours for different strains of MRS A, Two are hospital acquired strains and the third is a community acquired strain.
  • Figure 8 is a plan view of a series of petri-dishes showing the effect of the antimicrobial material containing 5wt% clay (top) and 12.5wt% clay (bottom) after immersion in fresh aliquots of water for 16, 24, 48, and 72 hours.
  • the present polymer-clay composite material comprises two layers, a first layer containing a higher concentration of the clay and a second layer containing a lower concentration of the clay.
  • the first layer may be placed in contact with the wound to produce a fast-acting, quick-release of iodine to the infected area.
  • the second layer with a lower concentration of clay may be placed in contact with the wound to produce a sustained iodine release of up to 8 days according to one specific
  • the present material provides a visual colour change from brown to colourless once the antimicrobial iodine has been consumed. Accordingly, a healthcare worker is capable of identifying visually if a wound dressing requires replacement.
  • the wound dressing may also comprise a hydrophobic layer to provide a waterproof dressing which may be worn conveniently in - ⁇ ⁇ wet environments.
  • the present antimicrobial material is also suitable for use in other applications such as water purification, surface coatings for medical and dental devices and packaging within the pharmaceutical industry
  • the antimicrobial material may he synthesised conveniently from a slurry of a first polymer complexed with iodine, a second polymer and a clay which is then dried.
  • the clay is heterogeneously distributed in the two self-stratifying layers of the resulting construct. It is considered that one mechanism for performance may be due to the clay platelets combining with the polymers to influence the outward flow path of iodine which is advantageous for a controlled, sustained rate of iodine release and effective treatment of the wound.
  • the clay platelets may act to create an indirect path along which the iodine must pass when exiting the material.
  • the present polymer composite is, in one mode of application, able to draw liquid to the top of the dressing. This is referred to a 'wicking in wound care technology and is particularly suitable for treating wounds with excess exudate. The wicking mechanism acts to draw exudate away from the wound and in turn promotes healing.
  • an antimicrobial material was synthesised by mixing a commercially available aqueous solution of poly( vinyl pyrrolidone complexed iodine [PVP-b] (formula 1) with a second water soluble polymer, polyvinyl alcohol) [PVOH] (formula 2) and CloisiteTM Na + to form a slurry. The slurry was then dried to yield a polymer composite.
  • PVP-b poly( vinyl pyrrolidone complexed iodine
  • PVH polyvinyl alcohol
  • the clays suitable for use with the preferred embodiment of the invention are layered minerals in which each individual layer is one nanometre thick. Referring to figure 1 both individual 101 and stacks of clay layers or platelets 102 are dispersed throughout the resulting polymer composite 104.
  • an unusual feature of the PVP- h PVOH/clay composite is that during the drying process the present material forms self- stratified films fSSF).
  • the clay platelets 101 provide a dual function by compatibilising the PVP-fe and PVOH within the SSF and increasing the number of deviations in the path 103 that the
  • the platey clay structure 101 may contribute to the controlled, sustained release of the antimicrobial agent 100 at a predetermined rate from the clay/polymer composite 104.
  • the present SSF advantageously comprises a first layer 200 and a second layer 201.
  • the first layer 200 is visually different to second layer 201 , in that first layer 200 may be described as light brown in appearance whilst second layer 201 may be considered darker brown.
  • An advantage of the double layered antimicrobial material 203 is that the release profile of iodine 100 depends on which face of the material is applied to the wound and in particular to the bacteria.
  • first layer 200 comprises a contact face 204 for positioning in contact with the wound and second layer 201 comprises a corresponding contact face 205 to provide an alternative face to contact the wound.
  • the time period over which the iodine is released from the material may then be selected as desired by placing the material in contact with the wound via either one of the contact faces 204, 205.
  • the present antimicrobial material 203 is therefore particularly suitable for use in wound dressings as healthcare professionals have the option to choose between two modes of use when determining the most appropriate form of treatment.
  • the combination of the two layers has the ability, when the darker layer 201 is applied to the wound, to draw water to the top of the dressing (referred to as SvkMng') to remove excess exudate from the wound.
  • SvkMng' draw water to the top of the dressing
  • Staphylococcus aureus is a Gram-positive bacteria skin commensal which is often found in infected wounds.
  • Escherichia coli and Pseudomonas aeruginosa are both Gram-negative bacteria which have an outer membrane containing lipopolysaccharide which protects the bacteria from certain antimicrobials which would normally damage the inner
  • the available antimicrobial agent, iodine may be present in the antimicrobial material in the range 0.1 and 15 wt%, 3 and 7,5 wt%, and 4.5 and 6 wt%. According to the specific implementation the iodine was present in the antimicrobial material at 6 wt%.
  • the bentonite, CloisiteTM Na + may be present in the antimicrobial material in the range between 0.1 to 95 wt%, 1 to 50 wt%, 2 to 30 wt% or 5 to 20 wt%. According to the specific implementation the CloisiteTM Na + was present at 12.5 wt%. According to further specific implementations the clay mineral may be chosen from a group of natural or synthetic fibrous or layered materials including, but not limited to kaolin, hal!oysite, talc, montmorillonite, bentonite hectorite, saponite, vermiculite, mica, attapulgite, or sepiolite and Cloisite IM Na + .
  • the second water soluble polymer poly(vinylalcohol) (formula 2), provides cohesion and encourages the formation of a robust film of the antimicrobial material.
  • Poly(vinylalcohol) may be present in the antimicrobial material in the range 30 and 40 wt%. According to the specific implementation the poly(vinylalcohol) was present at 35 wt%.
  • the second water soluble polymer may optionally be chosen from a group of poly(vinylacetate), poly(vinylalcohol), poly(ethylvinylalcohol), polyamide, poly(aniline), poly(acrylonitrile), po!y(pyrrole), poly(N-vinylcarbazole), poly(N-vinylimidazole), poly(2-vinylpyridine-co-styrene-co- divinylbenzene), poly(acetylene), starch, chitosan, cellulose or poly( vinyl pyrrolidone) (PVP).
  • PVP poly(vinylacetate), poly(vinylalcohol), poly(ethylvinylalcohol), polyamide, poly(aniline), poly(acrylonitrile), po!y(pyrrole), poly(N-vinylcarbazole), poly(N-vinylimidazole), poly(2-vinylpyridine-co-styrene-co- divinyl
  • the first water soluble polymer, poly( vinyl pyrrolidone) and complexed iodine (formula 1) may be present in the antimicrobial material in the range 50 and 60 wt%, 52 and 59 wt%, and 52 and 57 wt%. According to the specific implementation the poly(vinyl pyrrolidone) and complexed iodine (formula 1) was present at 52.5 wt%.
  • the poly( vinyl pyrrolidone) acts as an iodophor which stabilises the complexed iodine to reduce any allergenic effects and increase iodine solubility.
  • polyvinyl pyrrolidone acts as a reservoir which releases slowly active iodine from its complex-bound form. As the iodine is rendered inactive following the destruction of microorganisms further iodine is released, maintaining an equilibrium until the reservoir is completely used, In vitro growth iahibitioB assay
  • MH Mueller Hinton agar was inoculated with 1 x 10 s cfu/ml broth culture of each test organism. The culture was spread uniformly over the surface of the petri dish and allowed to dry, A single 2cm z dressing sample was placed in the centre of the inoculated petri dish and the lid replaced. For each organism six replicates of each dressing sample were tested. For each experiment a positive control was created by inoculating the test organism onto MH agar which was then incubated without a dressing sample. A negative control was also produced by placing uninoculated MH agar in the laminar flow cabinet for the duration of the experiment. This was then incubated at 37°C for 24 hours to ensure that there was no microbial growth.
  • iodoflex ® (Cadexomer Iodine) demonstrated a significant degree of activity against all three test bacteria, Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa, while other antimicrobial dressings varied in action towards each species.
  • Iodine is rapidly bactericidal but has a short duration of action.
  • An objective of the present invention is to provide a wound dressing which is able to deliver a controlled release of iodine over a prolonged period of time.
  • Dressings were prepared using two water soluble polymers; poly( vinyl alcohol) [PVOH] which provided cohesion to the material and po3y( vinyl pyrrolidone) [PVP] which stabilised the active antimicrobial ingredient, iodine.
  • PVOH poly( vinyl alcohol)
  • PVP po3y( vinyl pyrrolidone)
  • the dressings were prepared containing di ffering concentrations of available iodine: 1, 2, 3, 4.5, 6, 7.5 and 8.5 wt%.
  • the dressings were cut into 2 cm 2 samples and placed in a petri dish to be sterilised by UV irradiation for 15 minutes using a Mini - V/PCR Telstar prior to testing.
  • the irradiated dressing was placed face down onto the inoculated surface of the agar.
  • Pseudomonas aeruginosa 502 was the least susceptible
  • the effect of the addition of clay platelets of CloisiteTM Na + on the release of the antimicrobial agent from the dressings was investigated.
  • the concentration of available active iodine in the dressing was fixed at 5-6 wt%.
  • Table 1 shows the composition of the test dressings that were used during the experiment. All the above formulations were produced as unsupported films as well as cast onto cardboard. A pure cardboard sample and a sample containing PVP-I2 coated on cardboard were used as controls. A total of 26 different dressing samples were tested; 12 unsupported films and 13 cardboard backed films. The dressings were cut into 2cm 2 samples and sterilised as described above.
  • Figure 4 is an illustration of the composition of the dressing samples.
  • the active agent 401 is iodine
  • the layered silicate 400 is CloisiteTM Na +
  • the stabilizing polymer 402 is poly( vinyl pyrrolidone)
  • the supporting polymer 403 is poly( vinyl alcohol).
  • the control groups 1 and 2 are 404 and 405 respectively.
  • the groups labelled 406 and 407 comprise dressing samples with active iodine in 5-6 wt%.
  • the four unsupported samples containing 5-6 wt% iodine all produced a clear zone of inhibition 300 against each of the test microorganisms. After 24 hours against each bacteria, Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa, the dressings containing no clay platelets and 2.5 wt% platelets produced the largest zone of inhibition 300 and the sample containing 12.5 wt% clay platelets produced the smallest zone of inhibition 300.
  • the dressings demonstrated two different release characteristics depending on which face of the dressing (204, 205) was placed in contact with the agar.
  • the darker side (second layer 201) was placed in contact with the agar and incubated for 24 hours the sample curled and a small pool of brown liquid appeared on the top of the dressing.
  • the light side (first layer 200) was placed in contact with the agar and incubated for 24 hours it remained flat and produced a larger zone of inhibition 300 relative to the dark side.
  • the first layer 200 also appears to have the propensity to draw liquid through the second layer 201 and collect it in a pool at the outer surface of the dressing. This may he particularly useful in the treatment of chronic wounds to absorb excess wound exudate.
  • Table 2 illustrates the effect when different faces of the dressing 204, 205 w ere placed in contact with the agar.
  • the dressing curls so the ZOI cannot be measured from the edge of the dressing.
  • the ZOI was measured as the surface area of a circle or oval (mm 2 ) depending on the shape of the zone.
  • a dressing that is able to provide sustained delivery of low doses of free iodine has the advantage of delivering an antimicrobial action against a wide range of microorganisms with a lower potential for selecting resistant strains or inducing cytotoxic effects.
  • Cloisite I M Na + platelet concentration has been found to effectively extend the time over which iodine is available for antimicrobial activity.
  • the area of the zone of inhibition 300 produced was measured after 24 hours incubation at 37°C.
  • the used dressings were then transferred to a fresh agar plate inoculated with the same test organism.
  • the samples were then incubated for a further 24 hours at 37°C.
  • the zone of inhibition 300 was measured and the dressing transferred to another fresh agar plate inoculated with the same organism. This experiment was then repeated every day for seven days to test the efficacy of the antimicrobial agent over a period of a week.
  • a PVGH/PVP-I 2 /Clay 12.5 wt% dressing was noted to be visually different with one side light coloured (corresponding to the layer 200) and the other side darker in colour
  • the PVOH/PVP-b/Clay 12.5 wt% dressing containing 6 wt% iodine still produced a clear zone of inhibition 300 against, each test microorganism after 120 hours of continued use.
  • the zones of inhibition 300 produced were largest against Staphylococcus aureus 600, 601, than Escherichia coli 602, 603 and smallest against Pseiidomonas aeruginosa 604, 605.
  • clay platelets 101 in the form of CloisiteTM Na + to a self-stratified film prepared using polyvinyl alcohol) and poly(vinyl pyrrolidone) containing 5-6 wt% active iodine produced a dressing which was effective against Staphylococcus aureus,
  • Escherichia coli and Pseudomonas aeruginosa for at least 120 hours.
  • Figure 6 shows Time/Kill Studies against Staphylococcus aureus, Escherichia coli and Pseiidomonas aeruginosa and provides a comparison of the effective iodine release from the dark (205) and light (204) faces of the dressing.
  • Figure 7 demonstrates that the dressing produced a clear zone of inhibition against all three strains of MRS A for 96 hours: USA 300 with the darker layer 201 and darker face 205 in contact with the agar 700; and with the lighter layer 200 and lighter face 204 in contact with the agar 701; EMRSA-16 with the darker layer 201 and darker face 205 in contact with the agar 702; and with the lighter layer 200 and lighter face 204 in contact with the agar 703; EMRSA- 15 with the darker layer 201 and darker face 205 in contact with the agar 704; and with the lighter layer 200 and lighter face 204 in contact with the agar 705. All the dressings produced larger areas of inhibition of bacterial growth after 48 hours than they had produced after 24 hours.
  • the dark face 205 of the second layer 201 was observed to inhibit large zones of bacterial growth after 120 hours against USA 300 (700), EMRSA- 16 (702) and EMRSA-15 (704), Additionally, the dark face 205 was observed to be effective to kill USA 300 (700) and EMRSA-15 (704) after 144 hours.

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Medicinal Chemistry (AREA)
  • Polymers & Plastics (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Animal Behavior & Ethology (AREA)
  • Organic Chemistry (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Wood Science & Technology (AREA)
  • Environmental Sciences (AREA)
  • Inorganic Chemistry (AREA)
  • Agronomy & Crop Science (AREA)
  • Pest Control & Pesticides (AREA)
  • Plant Pathology (AREA)
  • Dentistry (AREA)
  • Epidemiology (AREA)
  • Zoology (AREA)
  • Hematology (AREA)
  • Materials Engineering (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Toxicology (AREA)
  • Dispersion Chemistry (AREA)
  • Biomedical Technology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Vascular Medicine (AREA)
  • Medicinal Preparation (AREA)
  • Materials For Medical Uses (AREA)

Abstract

La présente invention concerne un matériau composite antimicrobien comprenant un premier polymère contenant un hétéroatome complexé à l'iode ou une espèce contenant de l'iode, un second polymère destiné à favoriser la formation de matériau et une argile. Le matériau est approprié pour une utilisation tant que pansement pour fournir une libération contrôlée d'iode sur une période de temps souhaitée.
PCT/GB2016/050658 2015-03-13 2016-03-10 Matériau antimicrobien Ceased WO2016146972A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
GB1504305.2 2015-03-13
GB1504305.2A GB2536427A (en) 2015-03-13 2015-03-13 An antimicrobial material

Publications (1)

Publication Number Publication Date
WO2016146972A1 true WO2016146972A1 (fr) 2016-09-22

Family

ID=53016109

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/GB2016/050658 Ceased WO2016146972A1 (fr) 2015-03-13 2016-03-10 Matériau antimicrobien

Country Status (2)

Country Link
GB (1) GB2536427A (fr)
WO (1) WO2016146972A1 (fr)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN110251719A (zh) * 2019-06-26 2019-09-20 西北师范大学 外敷材料用角蛋白基高分子复合海绵状气凝胶的制备方法

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2009027971A2 (fr) * 2007-08-27 2009-03-05 H2Q Water Industries Ltd. Polymeres antimicrobiens
US20090191258A1 (en) * 2008-01-24 2009-07-30 Mankovitz Roy J Iodine-containing compositions
WO2010060094A1 (fr) * 2008-11-24 2010-05-27 Acrymed, Inc. Constructions stratifiées antimicrobiennes

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101130105A (zh) * 2007-09-13 2008-02-27 郑州大学 聚维酮碘水凝胶创伤敷料及其辐射制备方法
CN104474588B (zh) * 2014-11-25 2016-08-24 北京奥精医药科技有限公司 一种聚氨酯医用抗菌材料及其制备方法

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2009027971A2 (fr) * 2007-08-27 2009-03-05 H2Q Water Industries Ltd. Polymeres antimicrobiens
US20090191258A1 (en) * 2008-01-24 2009-07-30 Mankovitz Roy J Iodine-containing compositions
WO2010060094A1 (fr) * 2008-11-24 2010-05-27 Acrymed, Inc. Constructions stratifiées antimicrobiennes

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN110251719A (zh) * 2019-06-26 2019-09-20 西北师范大学 外敷材料用角蛋白基高分子复合海绵状气凝胶的制备方法

Also Published As

Publication number Publication date
GB201504305D0 (en) 2015-04-29
GB2536427A (en) 2016-09-21

Similar Documents

Publication Publication Date Title
Konop et al. Certain aspects of silver and silver nanoparticles in wound care: a minireview
Huang et al. Synergistic combination of chitosan acetate with nanoparticle silver as a topical antimicrobial: efficacy against bacterial burn infections
CN1121877C (zh) 伤口护理的改进
RU2553363C2 (ru) Антисептические композиции и их применения
Dave et al. Biomedical evaluation of a novel nitrogen oxides releasing wound dressing
US20130171224A1 (en) Treatment of biofilms
BRPI0710135A2 (pt) curativos de ferimento de múltiplas camadas
White et al. Silver sulphadiazine: a review of the evidence
WO2012136968A1 (fr) Composition comprenant des ions métalliques antimicrobiens et un tensioactif cationique quaternaire
US10874108B2 (en) Anti-microbial compositions
US20220347138A1 (en) Wound care product
CN104487102A (zh) 包含生物纤维素和银纳米颗粒的创伤敷料
EP1635850B1 (fr) Antimicrobien a l'argent
US9723843B2 (en) Family of silver (I) periodate compounds having broad microbial properties
Lalueza et al. Strong bactericidal synergy between peracetic acid and silver-exchanged zeolites
WO2016146972A1 (fr) Matériau antimicrobien
US9566363B2 (en) Microbicidal composite material
Moore A new silver dressing for wounds with delayed healing
GB2402880A (en) Antimicrobial silver complexes
US11554137B2 (en) Composition and method for arresting blood flow and for forming a persistent microbial barrier
Ip Antimicrobial dressings
CN202505597U (zh) 含金属离子抗菌剂的负压治疗创面贴
White The use of topical antimicrobials in wound bioburden control
Hus et al. Nanocrystalline silver layer of knitted polyester outperforms other silver-containing wound dressings in an in vitro wound model
US20240148932A1 (en) Wound dressing with preventive biofilm additive

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 16710303

Country of ref document: EP

Kind code of ref document: A1

NENP Non-entry into the national phase

Ref country code: DE

122 Ep: pct application non-entry in european phase

Ref document number: 16710303

Country of ref document: EP

Kind code of ref document: A1