Classifications

• • 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
  • A01N25/34—Shaped forms, e.g. sheets, not provided for in any other sub-group of this main group
• • 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
  • A01N55/00—Biocides, pest repellants or attractants, or plant growth regulators, containing organic compounds containing elements other than carbon, hydrogen, halogen, oxygen, nitrogen and sulfur
• • 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
  • A61L15/42—Use of materials characterised by their function or physical properties
• • 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
  • A61L15/42—Use of materials characterised by their function or physical properties
  • A61L15/46—Deodorants or malodour counteractants, e.g. to inhibit the formation of ammonia or bacteria
• • 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
  • A61L2300/20—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing organic materials
  • A61L2300/204—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing organic materials with nitrogen-containing functional groups, e.g. aminoxides, nitriles, guanidines
  • A61L2300/208—Quaternary ammonium compounds
• • 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
  • A61L2300/40—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
  • A61L2300/404—Biocides, antimicrobial agents, antiseptic agents

Definitions

• the present invention relates to an anti-microbial composition for use as a component of a topical anti-microbial device; in particular an absorbent device, such as a medical absorbent device, for example an absorbent wound dressing, and an absorbent device for the personal care sector; and a medical cushioning device; a process for the manufacture of such devices, and to a method of prophylactic and therapeutic use of the device
• the term 'absorbent component' as used herein refers to any conformable component of an antimicrobial device for the antimicrobial treatment of animate surfaces, such as the skin of a human or animal.
• the absorbent component comprises a synthetic or natural porous absorbent material that is substantially insoluble in a relevant bodily fluid, such as wound exudate, menses or urine, but absorbs the fluid.
• the absorbent component may be in a medical absorbent device, such as an absorbent wound dressing, or in a non-medical absorbent device for the personal care sector.
• the absorbent component has a proximal face, as defined herein, which in use of the device will be in direct or fluidic contact with the skin of a human or animal.
• 'absorbent device' as used herein includes medical absorbent devices and non-medical absorbent devices, as defined herein.
• an absorbent device comprising a water-insoluble antimicrobial absorbent material as defined herein, in which an absorbent component cushioning devices exudate migration and/or absorption and retention of a relevant bodily fluid, such as wound exudate when in a medical absorbent device, such as an absorbent wound dressing, or such as menses or urine when in a non-medical absorbent device, such as a disposable sanitary device.
• a relevant bodily fluid such as wound exudate when in a medical absorbent device, such as an absorbent wound dressing, or such as menses or urine when in a non-medical absorbent device, such as a disposable sanitary device.
• Absorption of a relevant bodily fluid may occur in two dimensions (for example in an absorbent dressing or a sanitary towel), or three dimensions (for example in a deep-wound dressing or a tampon).
• the term 'absorbent material' as used herein is defined herein under "absorbent component" above.
• Such an absorbent material may be in the form of fibres, such as in an, often non-woven, fabric or a more random assembly of fibres, for example of randomly spun fibres; it may be in the form of a particulate. It may have fluids (including air) in its interstices and/or synthetic or natural biological or chemical agents in its interstices and/or its structural members.
• 'antimicrobial' as used herein in relation to a therapeutically active material includes materials which have
• MRSA Methicillin-resistant Staphylococcus aureus
• Clostridium difficile Salmonella typhimurium, Leigonella, Listeria monocytogenes and Escherichia coli
• antimycotic activity including against one or more of Aspergillus niger and Candida albicans, and/or
• 'antimicrobial device' as used herein means a device for the antimicrobial treatment of animate surfaces, and includes
• a medical device which is an absorbent device, such as an absorbent wound dressing used in the treatment of acute wounds, including surgical wounds, and chronic and burn wounds; an ostomy device, or a surgical or dental sponge; a non-medical device which is an absorbent device, such as one for use in the personal care sector, in particular for disposable sanitary devices such as nappies (diapers), disposable nappies and training pants, and feminine care products, for example, tampons, sanitary towels, or napkins and pant liners, and incontinence products, and
• a medical device which is an absorbent or non-absorbent cushioning device, such as a cushioning layer or cushioning device used in the prophylaxis or treatment of wound precursors, as defined herein, and chronic wounds, including pressure sores and/or ulcers.
• an absorbent or non-absorbent cushioning device such as a cushioning layer or cushioning device used in the prophylaxis or treatment of wound precursors, as defined herein, and chronic wounds, including pressure sores and/or ulcers.
• biocompatible refers to any material which does not induce adverse effects such as immunological reactions and/or rejections in a human or animal.
• biodegradable refers to any material which can be degraded and bioresorbed into the physiological environment.
• biodegradable materials include carboxymethylcellulose materials, carboxymethylchitosan materials, hyaluronic acid- and alginate-based materials; and certain copoly(etheresters), and poly(alkylene oxides).
• conformable container herein in relation to the absorbent material in an absorbent component in an absorbent device refers to any container, such as an envelope, pouch or sachet.
• Such a container may be formed by the proximal cover of a synthetic or natural layer or sheet material being attached to a dressing backing layer.
• a container may be, for example a stand-alone envelope, pouch or sachet, which in use lies between the wound and the backing layer, and may be attached to a dressing backing layer, and may be an 'inner container', contained in another stand-alone conformable Outer container').
• 'cushioning component' refers to any conformable component of a cushioning device, or a cushioning device which consists essentially of such a component, which may be used in the treatment or prophylaxis of wound precursors, as defined herein and chronic wounds, on or in the skin of a human or animal, or in the tissue underlying it. It comprises a cushioning material that is substantially insoluble in a relevant bodily fluid,
• the term 'cushioning device' as used herein refers to any conformable medical device, which is used to relieve pressure on a pressure-sensitive area of a human or animal, and acts as a source of topical therapeutic agents.
• the cushioning device is thus used for the prophylaxis and/or treatment of wound precursors, as defined herein, and chronic wounds, including pressure sores and ulcers on or in the skin, or in the tissue underlying it. .
• 'cushioning material' is the cushioning material in a medical cushioning device or cushioning component, and is a soft, flexible often polymeric material that is substantially insoluble in a relevant bodily fluid. Such materials may also often be hydrophobic.
• aqueous in the context of an aqueous medium is meant herein that the medium comprises at least 85%, for example at least 90%, such as at least 95% w/w water.
• the terms "medical” and “non-medical” in relation to a device herein are as defined herein under “antimicrobial device", and may relate to an absorbent medical or non-medical device or a non-absorbent medical cushioning device.
• micro in relation to a particulate or fibrous material herein means that the majority of particle or fibre diameters in the material are less than 100 micrometres.
• nano in relation to a particulate or fibrous material herein means that the majority of particle or fibre diameters in the material are less than 100 nanometres.
• non-biodegradable refers to any material which cannot be degraded and bioresorbed into the physiological environment.
• non-biodegradable materials include polyalkylenes, such as polyethylene, polypropylene and polybutylene, and combinations thereof.
• non-woven in relation to fabrics in the absorbent component means that the majority of fibres in the fabric are neither woven nor knit together, and are typically manufactured by putting small fibres together to form a sheet or web, and then binding them together mechanically, with an adhesive, or by thermal bonding, in particular by spin bonding.
• the term 'organic or inorganic acyl' as used herein includes organic acid residues such as carboxyl and inorganic acid residues such as sulpho.
• the term 'partially organic or inorganic acylhydrocarbyl substituted polysaccharide' means a polysaccharide derivatised by optionally salified HORO groups, where HOR is a hydrocarbyl oxoacid residue.
• polysaccharide' as used herein means any polymeric carbohydrate structure, formed of repeat monomer units which are monosaccharides joined together by glycosidic bonds, with two free hydroxyl functions and optionally one amine function per monomer unit, typically having between 200 and 2500 monomer units in the polymer molecule.
• These structures include linear homopolysaccharides, such as celluloses, chitosans and alginates.
• the term also includes derivatised polysaccharides, such as carboxymethyl celluloses and carboxymethyl chitosans.
• substitution may take place at any hydroxyl position and/or at the amine group up to a hypothetical mean maximum degree of conversion of 2 hydroxyl groups per monomer unit of the polysaccharide.
• the average degree of substitution in the derivatised polysaccharides used in devices is often less than 0.8, such as less than 0.7, for example less than 0.6.
• the average molecular weight of such a polysaccharide is often between 3800 to 20,000 daltons. Such polysaccharides are substantially insoluble in water.
• proximal in relation to a face of a component in a device is meant herein that the face is a body-facing face in general or a wound-facing face in a wound dressing in use.
• distal in relation to a face of a component in a device is meant herein that the face faces away from the body in general or away from a wound in a wound dressing.
• substantially water-insoluble in relation to a material is meant herein that the material is soluble in an aqueous medium to less than 1 % w/w.
• synthetic herein means any material that is not found in nature, and the term “semi-synthetic” means made from naturally occurring biomaterials. Examples include respectively plastics polymers and derivatised polysaccharides.
• water-soluble' in the context of a material is meant herein that the material is soluble in an aqueous medium to more than 5% w/w.
• wound in relation to the present invention means any soft tissue with compromised integrity, including acute wounds, such as surgical and infectious disease wounds; chronic wounds, such as diabetic ulcers or venous leg ulcers; and burns.
• wound contact integer includes a component in a wound dressing which comprises a porous absorbent component and optionally an elastically resilient, for example a foam, wound filler which lies distally of the absorbent component.
• wound precursor herein means any condition on or in the skin of a human or animal, or in the tissue underlying it, which in the absence of treatment is at substantial risk of developing into tissue of compromised integrity, such tissue including chronic wounds, including pressure sores, ulcers and infected wounds.
• tissue of compromised integrity such tissue including chronic wounds, including pressure sores, ulcers and infected wounds.
• Such conditions on or in the skin of a human or animal or in the tissue underlying it include discomfort, inflammation, pain and haematoma, which may be caused or exacerbated by pressure on the skin.
• therapeutically active materials which are typically antimicrobials
• therapeutically active devices such as topical medical devices, for example wound dressings, and topical non-medical absorbent devices, for example for the personal care sector.
• therapeutically active materials have good activity in contact with wound exudate, for example when in a dressing component which has a proximal surface, and that they and the other component materials in the compositions are biodegradable and biocompatible with human or animal tissue, as well as more preferably being odourless, and when in a dressing component having wound healing capability.
• such a therapeutically active material should be in a water-insoluble form which does not dissolve into solution to be uncontrolledly released from the dressing to any significant extent. This is particularly desirable for a wound dressing comprising an antimicrobial composition in view of the regulatory burden faced by antimicrobial dressings in which release of a therapeutically active component of the dressing into a wound occurs.
• the therapeutically active component of the dressing is an ionic material that is soluble when exposed to a highly aqueous medium such as a bodily fluid on a body surface or wound exudate, in particular in the latter case at the pH levels found in some chronic wounds at a typical patient body temperature.
• a water-soluble derivatised quaternary ammonium salt as defined as a biocidal component of a water-soluble composition for the treatment of inanimate surfaces, such as floors. Since the derivatised quaternary ammonium salt is only used on inanimate surfaces, such as floors, the other component materials in the compositions may be non-biodegradable and not biocompatible with human or animal tissue, as well as not being odourless and not having specific wound healing capability. It is also known to use a water-soluble underivatised quaternary ammonium salt as topical antimicrobials, for example in therapeutically active compositions.
• a very significant technical problem and disadvantage of such prior art compositions is the water-solubility and uncontrolled release from such a product of the underivatised quaternary ammonium salt. This is potentially a problem and disadvantage not only for any such materials in any topical medical absorbent devices, for example wound dressings, but also in topical non-medical absorbent devices, for example for the personal care sector, for the treatment of animate surfaces,
• the latter occurs to a significant extent when the composition is exposed to a highly aqueous medium at a typical patient body temperature, such as a bodily fluid on a body surface or wound exudate, in particular a bodily fluid on a body surface or at the pH levels found in some chronic and burn wounds.
• a highly aqueous medium at a typical patient body temperature such as a bodily fluid on a body surface or wound exudate, in particular a bodily fluid on a body surface or at the pH levels found in some chronic and burn wounds.
• This can present a risk of only short-term efficacy of the device and, in the case of wound dressings, a risk of resultant overdosing and the considerably higher regulatory burden faced by dressings in which release of a therapeutically active component into a wound occurs.
• Another technical problem of the prior art is that the longer-term stability of the derivatised quaternary ammonium salt in an aqueous fluid is sub-optimal.
• compositions may be non-biodegradable and not biocompatible with human or animal tissue, as well as not being odourless and not having specific wound healing capability.
• compositions for an antimicrobial device such as a medical device such as wound dressings, and a non-medical device, such as one for use in the personal care sector, which composition comprises a water-insoluble form of a quaternary ammonium salt, which is not released or only controlledly and relatively slowly released, on contact with bodily fluids of a patient or user.
• a composition should have longer-term stability on contact with an aqueous fluid. This is especially the case when it is exposed to a highly aqueous medium, such as a bodily fluid on a body surface or wound exudate, in particular in the latter case at the pH levels found in some chronic wounds.
• a composition for an antimicrobial device which is non-toxic, odourless, and biocompatible with human or animal tissue, and preferably is biodegradable, and when in a dressing component has wound healing activity.
• a solid substantially water-insoluble antimicrobial composition for an antimicrobial device comprising
• each of R 1 , R 2 and R 3 is an optionally substituted hydrocarbyl group
• R 4 is an optionally substituted hydrocarbylene group
• a topical anti-microbial device comprising a solid substantially water-insoluble antimicrobial composition of the first aspect of the present invention.
• the device may be an absorbent device, such as a medical absorbent device, for example an absorbent wound dressing, an absorbent device for the personal care sector; and/or a medical cushioning device.
• the antimicrobial composition of the first aspect of the present invention is often in particular comprised in an absorbent material in an absorbent component, but may be comprised another integer of the absorbent component, such as the proximal cover of a conformable container, which contains the absorbent material.
• the antimicrobial composition is often comprised in a cushioning material in a cushioning component, but may be comprised another integer of the cushioning component.
• the derivatised quaternary ammonium salt in the composition of this first aspect of the present invention is highly advantageous for use as an antimicrobial material in medical and non-medical absorbent devices and medical cushioning devices.
• the derivatised quaternary ammonium salt used in the composition is per se water-soluble, and has longer-term instability, in an aqueous medium, such as a bodily fluid on a body surface or wound exudate, in particular at the pH levels found in some chronic and burn wounds.
• the salt is rendered stable and substantially water-insoluble, but still therapeutically active, by being attached to and/or dispersed within a solid substantially water-insoluble carrier.
• compositions of the invention thus exhibit a surprising and advantageously diminished or negligible degree and rate of release by a bodily fluid on a body surface or wound exudate of the derivatised quaternary ammonium salt, in a an antimicrobial device for example in a medical device, such as a dressing.
• a medical device such as a dressing.
• the rate and degree of release can be controlled in particular by the choice of a) the derivatised quaternary ammonium salt, and
• the derivatised quaternary ammonium salt and solid substantially water-insoluble carrier may be linked by covalent bonding, optionally with condensation and/or cross-linking, as described further hereinafter.
• Treatment or prophylaxis of microbial infections using an antimicrobial composition according to this first aspect of the present invention does not cause microbial resistance, for example by
• bacteria such as Staphylococcus aureus (MRSA), Clostridium difficile, Salmonella typhimurium, Leigonella, Listeria monocytogenes and Escherichia coli,
• mycotic species including Aspergillus niger and Candida albicans, and/or viruses,
• compositions in particular not only when comprised in a dressing for wounds, including acute wounds, including surgical wounds, and chronic and burn wounds, but also when in topically applied personal care devices, and medical cushioning devices.
• Each of R 1 , R 2 , R 3 and R 4 may independently be oxa-substituted, preferably to produce R 1 , R 2 and R 3 optionally substituted hydrocarbyloxy groups, and, for example to produce an R 4 optionally substituted hydrocarbylene group with an internal ether linkage.
• Each of R 1 , R 2 and R 3 independently may be an optionally oxa-substituted alkyl group, preferably a lower alkyl group with 1 to 6 carbon atoms, such as a methyl, ethyl, propyl or butyl group, preferably a methyl group. Any propyl or butyl group is preferably attached in the 1 -position to the silicon atom.
• Each of R 1 , R 2 and R 3 is preferably a hydrocarbyloxy residue, for example a lower alkoxy group with 1 to 6 carbon atoms.
• Each of R 1 , R 2 and R 3 may thus suitably be, for example, a methoxy, ethoxy, propoxy, isopropoxy or butoxy group, preferably a methoxy group. Any component propyl or butyl group group is preferably attached in the 1 -position to the oxygen atom.
• the alkyl moiety in all the above groups may be branched or unbranched, and hence suitable butyl groups may be n-butyl, iso-butyl or tert. butyl groups. Most preferably, such R 1 , R 2 and R 3 groups are the same. The most preferred R 1 , R 2 and R 3 residue is a methoxy group.
• R 1 , R 2 and R 3 independently may also suitably be an aryl group, such as phenyl or tolyl, preferably phenyl.
• aryl group such as phenyl or tolyl, preferably phenyl.
• R 1 , R 2 and R 3 is an aryl group, such as phenyl.
• Each of R 1 , R 2 and R 3 independently may be an optionally oxa-substituted aralkyl group, preferably a lower alkyl group with 1 to 6 carbon atoms, such as a methyl, ethyl, propyl or butyl group, preferably a methyl group, substituted by an aryl group, such as phenyl or tolyl, preferably phenyl. Any component propyl or butyl group is preferably attached in the 1 -position to the silicon atom.
• Each of R 1 , R 2 and R 3 may be an aralkoxy group.
• Each of R 1 , R 2 and R 3 may thus suitably be, for example, a methoxy, ethoxy, propoxy, isopropoxy or butoxy group, preferably a methoxy group, substituted by an aryl group, such as phenyl or tolyl, preferably phenyl.
• R 1 , R 2 and R 3 is an aralkyl group, such as benzyloxy. Any component propyl or butyl group is preferably attached in the 1 -position to the oxygen atom.
• the alkyl moiety in all the above groups may be branched or unbranched, and hence suitable butyl groups may be n-butyl, iso-butyy or tert. butyl groups.
• R 4 is an optionally substituted hydrocarbylene group, which may be oxa-substituted, for example to produce an R 4 optionally substituted hydrocarbylene group with an internal ether linkage.
• R 4 may be an optionally oxa-substituted alkanediyl group, preferably a lower alkylene group with 1 to 6 carbon atoms, such as a methylene, ethan-1 ,2-diyl, propan-1 ,3-diyl or butan-1 ,4-diyl group, preferably an ethan-1 ,2-diyl group.
• R 5 is an optionally substituted hydrocarbyl group, which may be oxa-substituted, for example to produce an R 5 optionally substituted hydrocarbyl group with an internal ether linkage.
• R 5 may be an optionally oxa-substituted alkyl group, preferably a higher alkyl group with 8 to 22 carbon atoms, such as an octyl, decyl, dodecyl, tetradecyl, hexadecyl (cetyl or palmityl), octadecyl or eicosyl group.
• the alkyl moiety may be branched or unbranched, and oxa-substituted, for example to produce an R 5 optionally substituted unsaturated hydrocarbyl group with an internal ether linkage.
• Examples include 3,6-dioxa-substituted higher alkyl groups with 8 to 22 carbon atoms, more preferably such an octadecyl group, in which case, if the remaining N-substituents are methyl group, the derivatised quaternary ammonium salts is a derivatised benzethonium salt congener.
• R 5 may be an optionally oxa-substituted alkenyl group, preferably a higher alkenyl group with 8 to 22 carbon atoms, such as an octenyl, decenyl, dodecenyl, tetradecenyl, hexadecenyl, octadecenyl or eicosenyl group.
• the alkenyl moiety may be branched or unbranched, and oxa-substituted. It may be in a cis- or trans- configuration about any double bond.
• Examples include a cis-octadec-9-en-1 -yl moiety, which is an oleyl moiety; and a cis-, cis-octadeca- 9,12-dien-1 -yl moiety which is a linoleyl moiety,
• R 5 is preferably an unbranched unsubstituted higher alkyl group with 8 to 22 carbon atoms, more preferably such an octadecyl group.
• Each of the two remaining N-substituents other than the tris(hydrocarbyl or hydrocarbyloxy)-silylhydrocarbyl group of formula (I) and R 5 may independently be an alkyl group, preferably an optionally substituted lower alkyl group with 1 to 6 carbon atoms, such as a methyl, ethyl or propyl, preferably methyl.
• the alkyl moiety may be branched or unbranched, and hence suitable propyl may be n-propyl or iso-propyl.
• One of the groups may be an aralkyi group, such as benzyl, in which case, if the remaining N-substituent is a methyl group, the derivatised quaternary ammonium salts is a derivatised benzalkonium salt.
• the groups are the same and are methyl groups. Less preferably they may also independently be an aryl group, such as phenyl or tolyl, preferably phenyl.
• aralkyi groups such as benzyl.
• Each group may thus be an aryloxyalkyl group.
• the alkyl moiety may be branched or unbranched, and hence suitable propyl may be n- propyl or iso-propyl. Any component propyl or butyl group is preferably attached in the 1 -position to the nitrogen atom.
• one of the groups is an aryl or optionally oxa-substituted aralkyi group.
• the other may be an alkyl group, preferably methyl.
• any N- substituent in the derivatised quaternary ammonium salt will depend on the type and size of, and steric hindrance around the nitrogen atom of the derivatised quaternary ammonium salt caused by, the other substituent groups present.
• the anion of the derivatised quaternary ammonium salt for use in antimicrobial compositions of the first aspect of the present invention may be any pharmacologically acceptable anion.
• Such an anion of the derivatised quaternary ammonium salt may be selected from the anion of an inorganic acid, such as chloride, bromide, hydrogen sulphate, dihydrogen phosphate and/or hydrogen difluorophosphate.
• Such an anion of the derivatised quaternary ammonium salt may be selected from the anion of an organic acid, such as acetate, propionate, isobutyrate, iodobutyrate, valerate, caproate, alpha-hydroxyisobutyrate, glucoheptonate, benzoate, cinnamate, mandelate, isophthalate, 2-hydroxynapthoate, lactate, ascorbate, gluconate, salicylate, isethionate, succinamate, methanesulphonate.
• an organic acid such as acetate, propionate, isobutyrate, iodobutyrate, valerate, caproate, alpha-hydroxyisobutyrate, glucoheptonate, benzoate, cinnamate, mandelate, isophthalate, 2-hydroxynapthoate, lactate, ascorbate, gluconate, salicylate, isethionate, succinamate, methane
• Such an anion of the derivatised quaternary ammonium salt may also be selected from glucoheptonate, hydrogen tartrate, hydrogen adipate, hydrogen maleate hydrogen malate, hydrogen malonate, hydrogen glutamate, dihydrogen citrate, hydrogen succinate, hydrogen pamoate and/or hydrogen diglycolate.
• the anion may be a pharmacologically acceptable dianion, when there will be two derivatised quaternary ammonium cations per dianion, which may be then selected from a dianion of
• an inorganic diacid such as sulphate, hydrogen phosphate and/or hydrogen difluorophosphate, or
• an organic diacid such as succinate, malate, tartrate, malonate, diglycolate, malonate, succinate, maleate and tartrate.
• Examples of the salt thus include salts with an inorganic acid, such as chloride, sulphate and/or phosphate.
• Examples of the salt also include salts with an organic acid, such as a organic acid, for example acetate, benzoate, tartrate, adipate, lactate, maleate, glutamate, ascorbate, citrate, gluconate, succinate, pamoate, salicylate, isethionate, succinamate, mono-diglycollate, methanesulphonate, isobutyrate,/or glucoheptonate.
• a organic acid for example acetate, benzoate, tartrate, adipate, lactate, maleate, glutamate, ascorbate, citrate, gluconate, succinate, pamoate, salicylate, isethionate, succinamate, mono-diglycollate, methanesulphonate, isobutyrate,/or glucoheptonate.
• Favoured anions include halides, for example chloride and bromide.
• Preferred derivatised quaternary ammonium salts for use in antimicrobial medical compositions of the first aspect of the present invention include derivatised quaternary ammonium salt, wherein the quaternary ammonium salt is N- substituted by
• R 4 is a methylene, ethan-1 ,2-diyl, propan-1 ,3-diyl or butan-1 ,4-diyl group, preferably an ethan-1 ,2-diyl group,
• a group R 5 which is a dodecyl, tetradecyl, hexadecyl, octadecyl or eicosyl group, which may be branched or unbranched and/or oxa-substituted to produce a higher alkyl group with an internal ether linkage.
• More preferred derivatised quaternary ammonium salts for use in antimicrobial compositions of the first aspect of the present invention include derivatised quaternary ammonium salts such as N,N-dimethyl-N-octadecyl-N-2-(trimethoxysilyl)propylammonium chloride, N,N-dipropyl-N-octadecyl-N-2-(trimethoxysilyl)propylammonium hydrogen sulphate
• N,N-dipropyl-N-octadecyl-N-2-(trimethoxysilyl)propylammonium acetate N,N-dimethyl-N-octadecyl-N-2-(trimethoxysilyl)propylammonium benzoate, N,N-dipropyl-N-octadecyl-N-2-(trimethoxysilyl)propylammonium hydrogen tartrate,
• N,N-dimethyl-N-hexadecyl-N-2-(trimethoxysilyl)propylammonium dihydrogen phosphate N,N-dipropyl-N-hexadecyl-N-2-(trimethoxysilyl)propylammonium acetate, N,N-dimethyl-N-hexadecyl-N-2-(trimethoxysilyl)propylammonium benzoate, and
• derivatised quaternary ammonium salts for use in antimicrobial compositions of the first aspect of the present invention include derivatised quaternary ammonium salts such as
• N,N-dimethyl-N-octadecyl-N-2-(trimethoxysilyl)propylammonium benzoate and N,N-dipropyl-N-octadecyl-N-2-(trimethoxysilyl)propylammonium tartrate, and in particular N,N-dimethyl-N-octadecyl-N-2-(trimethoxysilyl)propylammonium chloride
• the derivatised quaternary ammonium salts comprise a tris(hydrocarbyl) or tris(hydrocarbyloxy) -silylhydrocarbyl group of formula (I):
• the primary purpose of the solid substantially water-insoluble carrier component is to render the derivatised quaternary ammonium salt stable and substantially water-insoluble, but still therapeutically active, by being attached to and/or dispersed within the solid substantially water-insoluble carrier.
• the compositions of the invention thus exhibit a surprising and advantageously diminished or negligible degree and rate of release by water of the derivatised quaternary ammonium salt. This is in particular the case when it is exposed to a highly aqueous medium, such as a bodily fluid on a body surface or wound exudate, in the latter case in particular at the pH levels found in some chronic and burn wounds.
• the rate and degree of release can be controlled in particular by the choice of the derivatised quaternary ammonium salt and the material(s) of the solid substantially water-insoluble carrier, in particular when the two components may be linked by covalent bonding optionally with condensation and/or cross-linking.
• the therapeutically active derivatised quaternary ammonium salt may be attached to a solid substantially water-insoluble carrier by hydrogen bonding and/or pairing of ions of opposite charges, and/or by covalent bonding, optionally with condensation and/or cross-linking.
• the solid carrier should be non-toxic and biocompatible with human or animal tissue, and must be substantially water-insoluble and have the capability of having the derivatised quaternary ammonium salt attached to and/or dispersed within it.
• the carrier may have any composition, form, structure or physical property, such as wet strength, that is compatible with its use in a device, in particular a wound dressing.
• Suitable materials for the carrier in medical and non-medical absorbent devices include the following polymeric materials:
• polyesters including aliphatic polyesters, polyurethanes, copoly(etheresters), polyamides, polycarbonates, poly(iminocarbonates) and polyorthoesters
• semi-synthetic polymeric materials such as those with reactive functions, by which the derivatised quaternary ammonium salt may be attached to the solid carrier, such as cellulose-based materials, such as carboxymethylcellulose materials, chitosans; and chitosan-based materials, such as carboxymethylchitosan materials, and alginate-based materials; and
• the carrier is preferably of a polyester, an alginate, a cellulose material or a chitosan material, or a derivative of such materials such as a carboxymethylcellulose material or a carboxymethylchitosan material, and in particular a polyester, especially when comprised in a wound dressing.
• Suitable carrier materials include materials
• polar groups such as ester, urethane, ether, amide, imine and hydroxyl functions, for example respectively on a polyester, copoly(etherester), polycarbonate, poly(iminocarbonate) or a polyorthoester; a polyurethane, a copoly(etherester), a polyamide, a poly(iminocarbonate), or a polysaccharide, by which the derivatised quaternary ammonium salt may be attached to the solid carrier by hydrogen bonding,
• ionic functions typically the anion of salts, such as of salified carboxylic acids, for example on a polysaccharide, by which the cation of the derivatised quaternary ammonium salt may be attached to the solid carrier by pairing of ions of opposite charges and/or
• reactive functions typically hydroxyl functions or oxide anionic functions, typically the anion of an alkali metal oxide, such as a sodium alkoxide group, for example on a polysaccharide, by which the derivatised quaternary ammonium salt may be attached to the solid carrier by covalent bonding optionally with condensation and/or cross-linking.
• reactive functions typically hydroxyl functions or oxide anionic functions, typically the anion of an alkali metal oxide, such as a sodium alkoxide group, for example on a polysaccharide, by which the derivatised quaternary ammonium salt may be attached to the solid carrier by covalent bonding optionally with condensation and/or cross-linking.
• reaction may occur between such a function in the polysaccharide and the silylhydrocarbyl group of formula (I):
• R 1 (R 2 ) (R 3 ) Si R 4 (I) the R 1 , R 2 and R 3 groups are the same and each is a methoxy group, condensation occurs with elimination of methanol or an alkali metal methoxide, such as sodium methoxide, respectively. It is also believed that reaction between such function in the polysaccharide and the silylhydrocarbyl group of formula (I) is facilitated by the presence of an alkali metal, in particular a sodium, cation.
• R 1 , R 2 and R 3 groups are the same and each is a methoxy group, has taken place, cross-linking via a reaction which comprises a condensation reaction between adjacent groups of formula (I):
• R 1 (R 2 ) (R 3 ) Si R 4 (I) may occur with elimination of methanol to form silyl ether cross-links between adjacent groups of formula (I).
• the carrier is of a cellulose-based material, such as a carboxymethylcellulose material, a chitosan-based material, such as a carboxymethylchitosan or an alginate
• hydrophilic materials are substantially water-insoluble materials, but are water-absorbent material, which will generally swell in contact with water, in some cases to become an elastic gel material, but maintain their structural integrity.
• the substantially water-insoluble, absorbent materials of the carrier in any form or structure are
• i) may be readily produced by conventional processes which are well-known to the skilled person, or ii) are described further in the patent prior art, including in the case of carboxymethylchitosans, our copending application GB 180426.4.
• compositions of the first aspect of the present invention include those comprising a derivatised quaternary ammonium salt which is
• the carrier may have any form, structure and physical property that is compatible with its use in medical and non-medical devices, including in particular a wound dressing.
• an absorbent composition for an absorbent device comprising a particulate form of the substantially water-insoluble carrier to which the derivatised quaternary ammonium salt is attached.
• the particulate may typically be a microparticulate as defined herein, having an average pre- absorption diameter in the micrometre scale, for example from about 0.1 to 10 microns and more particularly of from about 1 .2 to 4.0 microns.
• the particulate may have a mean pre-absorption size of the interstices between its particles of 1 to 50 microns, preferably between 3 and 35 microns, more preferably between 4 and 20 microns.
• a particulate composition when such a particulate composition is used in an absorbent device where the device is a wound dressing, unless it is all irremovably attached to a dressing backing layer, it cannot be used in direct contact with a wound, but must be contained in a conformable container.
• This container may optionally be an inner container for the absorbent material within an outer container, optionally bonded to each other, to a backing layer and/or to a wound filler.
• a second embodiment of the composition of the first aspect of the present invention provides an absorbent composition for an absorbent device comprising the derivatised quaternary ammonium salt and the substantially water-insoluble carrier to which it is attached as a random assembly of flexible fibres.
• the composition when such a composition is used in an absorbent device, it may be in the form of at least one piece of wadding, such as a cushion or pad.
• the fibres are optionally bonded to each other, to a backing layer and/or to a wound filler and may be contained in a conformable container, optionally as an inner container for the absorbent material within an outer container, in turn optionally bonded to each other, to a backing layer and/or to a wound filler.
• Such fibres are typically microfibres or nanofibres as defined herein, frequently having an average diameter (pre-absorption if the fibres are of a water-absorbent material) in the micrometre or nanometre scale, for example from about 50 nanometres to 50 microns, particularly of from about 0.1 to 10 microns and more particularly of from about 1 .2 to 4.0 microns
• the assembly of flexible fibres may have a mean pre- absorption pore size of 1 to 50 microns, preferably between 3 and 36 microns, more preferably between 4 and 25 microns, and more preferably between 5 and 20 microns.
• a composition that comprises a substantially water-insoluble carrier as a, for example non-woven, fabric As described further hereinafter, when such a composition is used in an absorbent device, it may be in the form of at least one piece of woven fabric or, typically non-woven fabric.
• the or each piece is optionally bonded to another, to a backing layer and/or to a wound filler and may be contained in a conformable container, optionally as an inner container for the absorbent material within an outer container, in turn optionally bonded to each other, to a backing layer and/or to a wound filler.
• the fibres in such a composition that comprises a substantially water-insoluble carrier as a, for example non-woven, fabric are preferably microfibres or nanofibres as defined herein.
• the fibres generally having a monofilament linear density of 0.1 to 30, preferably about 0.5 to 20, and more preferably 0.9 to 8, for example 1 3 to 5 decitex, and a strength of 0.8 to 2.2, such as 1 to 2, for example 1 .2 to 1 .8 cN/dtex.
• The, typically non-woven, fabric may suitably have a thickness of 30 to 200g/m 2 or more.
• the fibres are of a water-absorbent material. In such case, whilst they may swell in contact with water and may become an elastic gel material, they exhibit good maintained integrity and wet strength.
• the carrier material is often the only carrier material present.
• other materials for example strengthening polymeric materials, are present, often in the form of reinforcing fibres, in general microfibres or nanofibres as defined herein, which are intermingled and blended with the carrier fibres according to the invention.
• thermoplastic bicomponent fibres preferably comprising a polyolefin-containing polymeric material of which the largest part (by weight) consists of homo- or copolymers of monoolefins such as ethylene, propylene, 1 -butene or 4-methyl-l-pentene. These may be added, in a weight ratio of 1 :9 to 9:1 , for example of 1 :6 to 6:1 or 1 :3 to 3:1 . The addition of such materials may have a significant improving effect on the strength of the material in a non-woven fabric.
• an absorbent composition that comprises a substantially water-insoluble carrier as a foam, such as an open-cell foam.
• the carrier may be in the form of at least one piece of a, typically open-cell, foam.
• the or each piece is optionally bonded to another, to a backing layer and/or to a wound filler and may be contained in a conformable container, optionally as an inner container for the absorbent material within an outer container, in turn optionally bonded to each other, to a backing layer and/or to a wound filler.
• the foam absorbent material in the composition of the first aspect of the present invention may have a mean pre-absorption pore size of 1 to 50 microns, preferably between 3 and 35 microns, more preferably between 4 and 25 microns, and more preferably between 5 and 20 microns.
• the second aspect of the present invention provides a topical anti-microbial device comprising a solid substantially water-insoluble antimicrobial composition of the present invention, which may be an antimicrobial medical or non-medical absorbent device or a medical cushioning device.
• a medical device which is a wound dressing has an absorbent component for absorbing wound exudate from a wound during use, and will typically comprise the following non-limiting components:
• the wound dressing frequently comprises a wound contact integer attached to the proximal face of a backing layer of the dressing.
• the wound contact integer may consist essentially of an absorbent component for absorbing wound exudate from the wound during use, or may comprise an absorbent component lying in contact with the proximal face of a wound filler, in turn in contact with the backing layer of the dressing.
• the absorbent component may consist essentially of an absorbent material for absorbing wound exudate from the wound during use, or may comprise an absorbent material lying in contact with, and contained in, a conformable container. In such case, such an absorbent material must be irremovably attached directly or indirectly to a dressing backing layer and in use must not adhere to a wound on removal of the wound dressing from the wound.
• the absorbent component will comprise the absorbent material, usually in a conformable container, which comprises a layer or sheet proximal cover which is permeable to wound exudate and of a biocompatible material, lying between the wound and the dressing backing layer.
• the container may be formed by the proximal cover being attached to the dressing backing layer, or attached to the wound filler where the device is a wound dressing, in turn attached to a dressing backing layer.
• a conformable container may be in the form of a stand-alone envelope, pouch or sachet, which may be attached to the dressing backing layer, or attached to the wound filler where the device is a wound dressing, in turn attached to a dressing backing layer.
• the conformable container must itself (as an 'inner container') be contained in another conformable container (as an Outer container') which also comprises a proximal cover.
• the proximal cover of the outer container must be permeable to wound exudate and not adhere to a wound in use on removal of the wound dressing from the wound.
• the outer container may be formed by the proximal cover being attached to the dressing backing layer, or attached to the wound filler where the device is a wound dressing, in turn attached to a dressing backing layer.
• a conformable container may be in the form of a stand-alone envelope, pouch or sachet, which may be attached to the dressing backing layer, or attached to the wound filler where the device is a wound dressing, in turn attached to a dressing backing layer.
• the inner container would not adhere in use to a wound on removal of the wound dressing from the wound, but may itself still be contained in a conformable outer container.
• the substantially water-insoluble antimicrobial composition of the first aspect of the present invention may be or form part of one or more components of a device, such as a wound dressing.
• the antimicrobial composition of the first aspect of the present invention may essentially be or form part of one or more of the following components of an absorbent wound dressing:
• any conformable container which comprises the absorbent material which cover may be, for example in an outer container and/or an inner container contained in the outer container, each of which may more favourably be a stand-alone envelope, pouch or sachet, and/or
• the absorbent material in the wound dressing may consist essentially of the substantially water-insoluble antimicrobial composition of the first aspect of the present invention.
• the carrier in the composition of the first aspect of the present invention will be the absorbent material of the wound dressing, and suitable and preferred materials, sizes, forms and structures of the absorbent material will be as so described hereinbefore in relation to corresponding absorbent materials, forms and structures of the carrier of the antimicrobial composition.
• the absorbent material in the wound dressing may comprise the substantially water-insoluble antimicrobial composition of the first aspect of the present invention.
• suitable and preferred materials, sizes, forms and structures of the absorbent material may be as so described hereinbefore in relation to corresponding absorbent materials, forms and structures of the carrier of the antimicrobial composition.
• the composition of the first aspect of the present invention and/or the absorbent material in the wound dressing may be in the form of, for example, a particulate; fibres, frequently microfibres or nanofibres as defined herein, as a random assembly of flexible fibres, which may be in the form of at least one piece of wadding, such as a cushion or pad, or as an, often non- woven, fabric; and/or a foam, such as an open-cell foam.
• composition of the first aspect of the present invention and/or the absorbent material must be irremovably attached directly or indirectly to a dressing backing layer and in use must not adhere to a wound on removal of the wound dressing from the wound. Otherwise, the absorbent component in the wound dressing will usually comprise the composition of the first aspect of the present invention and/or absorbent material, in a conformable container.
• such a container will comprise a layer or sheet proximal cover which is permeable to wound exudate and of a biocompatible material, lying between the wound and the dressing backing layer.
• the container may be formed by the proximal cover being attached to the dressing backing layer, or attached to the wound filler where the device is a wound dressing, in turn attached to a dressing backing layer.
• a conformable container may be in the form of a stand-alone envelope, pouch or sachet, which may be attached to the dressing backing layer, or attached to the wound filler where the device is a wound dressing, in turn attached to a dressing backing layer.
• any conformable container may optionally comprise an antimicrobial composition of the first aspect of the present invention.
• the cover that is permeable to wound exudate and forms the proximal face of the above conformable container may consist essentially of, or comprise the substantially water-insoluble composition of the first aspect of the present invention.
• composition of the first aspect of the present invention in this embodiment of the second aspect of the invention may be in the form of, for example, an, often non-woven, in particular spun-bonded, fabric and/or a layer or sheet of an open- cell foam, which is permeable to wound exudate.
• the conformable container of which the relevant proximal layer or sheet cover which consists essentially of or comprises the substantially water-insoluble antimicrobial composition of the first aspect of the present invention must be contained in an outer container.
• such an outer container will also comprise a layer or sheet proximal cover which is permeable to wound exudate and of a biocompatible material, lying between the wound and the dressing backing layer.
• This proximal layer or sheet cover may alternatively or additionally, usually alternatively, consist essentially of or comprise the substantially water-insoluble antimicrobial composition of the first aspect of the present invention.
• composition of the first aspect of the present invention in this embodiment of the second aspect of the invention may be in the form of, for example, an, often non-woven, in particular spun-bonded, fabric and/or a layer or sheet of an open-cell foam, which is permeable to wound exudate.
• a medical device such as a wound dressing
• other medical devices of the first aspect of the invention which tend to be applied to other parts of the body and/or for other bodily fluids.
• non-medical devices such as for the personal care sector, particularly for disposable sanitary devices such as nappies (diapers) and incontinence products.
• the devices tend to be applied to other substrates, such as underwear, and/or for other bodily fluids, such as menses or urine.
• antimicrobial composition of the present invention with a derivatised quaternary ammonium salt comprised therein has been mainly in relation to absorbent carrier materials for use in medical and non-medical absorbent devices, and in particular to medical absorbent devices such as wound dressings.
• antimicrobial compositions of the present invention with a derivatised quaternary ammonium salt comprised therein include a cushioning composition.
• a cushioning composition for a cushioning device comprising a substantially water-insoluble carrier to which the derivatised quaternary ammonium salt is attached in the form of a body of a soft, flexible material.
• the cushioning composition may be comprised in a cushioning material in a cushioning component, or may essentially be the cushioning material.
• the cushioning component may be comprised in a cushioning device, or may essentially be the cushioning device.
• the cushioning composition will often essentially be the cushioning material.
• the cushioning component will often essentially be the cushioning device.
• the cushioning composition of the present invention with a derivatised quaternary ammonium salt comprised therein will be illustrated by the following non-limiting description mainly in relation to the cushioning device.
• the skilled person will appreciate that other integers may be present in the cushioning material, cushioning component or cushioning device, which are compatible with the use of the device as a medical cushioning device.
• the conformable cushioning device of the present invention may suitably be in any form or shape that is compatible with its functions of relieving pressure on a pressure-sensitive area of a human or animal, and acting as a source of topical therapeutic agents.
• the cushioning device is thus used for the prophylaxis and/or treatment of wound precursors, as defined herein, and chronic wounds, including pressure sores and ulcers on or in the skin, or in the tissue underlying it.
• It will often comprise, or consist essentially of an imperforate integer. Accordingly, It should preferably have a moisture vapour permeability (MVP) in the range of 250 to 4 500 g/m 2 /24hr, more preferably with an MVP) in the range of 250 to 2 500 g/m 2 /24hr, facilitating moisture vapour escaping normally from under it. It should preferably take up as little space as possible so that ⁇ cushioning device can be worn under ordinary human clothing or footwear (shoes etc.), or bedclothes without causing much inconvenience
• MVP moisture vapour permeability
• It may be a device which is not shaped to conform in use to a pressure-sensitive part of the body, an 'unshaped device', such as a layer or sheet or it may be shaped to conform in use to a pressure-sensitive part of the body, such as the feet or the sacrum, a 'shaped device'.
• parts of the body for example on each side of the torso and the back tend to be pressure-sensitive parts of the body, at risk of developing wound precursors and/or chronic wounds, including pressure sores, ulcers and infected wounds.
• Cushioning devices of the present invention may suitably be used on pressure- sensitive parts of the body, for example on each side of the torso and the back of such a patient who is known to be at risk of developing pressure sores and/or ulcers.
• the conformable cushioning device for application to a human or animal body is not shaped to conform to affected areas to which it is applied.
• Such cushioning devices are usually in the form which comprises a conformable component, or consists essentially of such a component in the form of at least one layer or sheet of a absorbent material.
• Such structures often have a shape such as an elongate strip, band or ribbon, a quadrilateral, such as a rectangle or oblong, or an equilateral, such as a square, or a round, but not necessarily regularly round, disc such as circular, elliptical or oval disc such as circular, elliptical or oval cushioning device.
• This embodiment of the first aspect of the present invention will typically have a thickness that tends to be constant and towards the lower figures in the ranges given hereinbefore for the thickness of the general cushioning device of the present invention; that is in the ranges of from 0.1 to 1 .5 cm, for example from 0.2 to 1 cm, such as from 0.3 to 0.5 cm.
• such cushioning devices may comprise a material which characteristically has a good permeability to water vapour, and at least part of the proximal face of which is inherently self-adhesive to skin, thus avoiding any need for a layer of pressure-sensitive adhesive around the periphery of its proximal face, or retaining strapping or other means of attachment.
• Such self-adhesion is usually relatively unaggressive, which is among the especially advantageous properties of a cushioning device with a proximal face comprising such a material.
• the present cushioning device may suitably be provided with conventional (generally pressure-sensitive) adhesive around the periphery of its proximal face, or retaining strapping or other appropriate means for it to be secured, which are well-known to the skilled person, or are described further in the patent or literature prior art.
• the present cushioning device may suitably be made of at least one piece, typically one piece, of foam. Two or more pieces are optionally bonded to each other.
• the foam may be a foamed plastics material, foam natural rubber or another foam material, preferably with a good permeability to water vapour. Suitable such materials include thermoplastic polyurethane foams. These are characteristically extremely soft and pliable.
• This form of the material may be an open-cell foam, that is one in which at least some of the pores in the material form the plurality of channels running between opposite faces, or it may be a closed-cell foam.
• the lower parts of the body for example the soles and heels of the feet and the sacrum, tend to be particularly pressure-sensitive parts of the body, where the risk of developing wound precursors and/or wounds referred to above tends to occur. This is especially the case in those patients with arthritis, diabetes or cardiovascular conditions who are not bedridden or chairbound.
• Such cushioning devices are usually shaped to conform in use to, and to be in direct or indirect contact with, a relevant body part when used in cushioning, relieving pressure on, and cushioning pressure-sensitive parts of the body such as the soles and heels of the feet and the sacrum, and protecting them against wound precursors and/or chronic wounds, including pressure sores, ulcers and infected wounds.
• a second form of the fifth aspect of the present invention is a shaped cushioning device that is one that is shaped to conform in use to the body over an affected area to which it is applied. It may suitably be used on pressure-sensitive parts of the body, for example on parts of the body of a patient who is not bedridden, but mobile or chairbound, and is known to be at risk of developing pressure sores and/or ulcers.
• Such a conformable, flexible cushioning devices of the present invention is in general shaped to conform to, for example, the foot or the sacrum.
• the thickness of such a cushioning device of the present invention tends to range between the lowest and highest figures in these ranges, that is in the ranges of from 0.3 to 5 cm, for example from 0.5 to 3 cm, such as from 1 to 1 .5 cm.
• the cushioning device has an increased thickness at the point where it is required to cushion the arch, or where the proximal face conforms in use to, for example the soft tissue over the sacrum, the cushioning device has an increased thickness at that point where it is required to cushion the sacrum.
• the opposite distal face does not conform in use to the same extent to the relevant part of the human body if at all.
• a cushioning device of this embodiment of the first aspect of the present invention will generally not need to be provided with means for it to be secured to the body of a patient who is potentially at risk, over the affected areas to which it is applied.
• Such cushioning devices are in general held in position over the affected parts, in the foot by conforming footwear, or in other parts of the body, for example over the sacrum, by clothing.
• it thus does not normally need to be provided with conventional adhesive or strapping means for it to be secured
• Any conforming footwear or clothing should not of course block the surfaces of this embodiment to such an extent that the moisture vapour permeability (MVP) of the cushioning device on the relevant part of the body is impaired, and in particular falls below 250 g/m 2 /24hr, and thus put a patient at risk of developing wound precursors and/or chronic wounds, including pressure sores, ulcers and infected wounds.
• MVP moisture vapour permeability
• the present cushioning device may suitably be made of at least one piece, typically one piece, of foam. Two or more pieces are optionally bonded to each other.
• the foam may be a foamed plastics material, foam natural rubber or another foam material, preferably with a good permeability to water vapour. Suitable such materials include thermoplastic polyurethane foams. These are characteristically extremely soft and pliable.
• This form of the material may be an open-cell foam, that is one in which at least some of the pores in the material form the plurality of channels running between opposite faces, or it may be a closed-cell foam.
• the conformable cushioning devices may suitably be made of a soft, pliable plastics material.
• Suitable materials for use in the cushioning devices the first aspect of the present invention include synthetic polymeric materials, with a good permeability to water vapour, such as
• elastomers for example one based on one or more alkylenes, such as ethylene, propylene and butylene, and styrene and combinations thereof,
• thermoplastic polyurethanes also preferred materials
• closed-cell foamed plastics materials for example a thermoplastic polyurethane closed-cell foam, closed-cell foamed natural rubber or any other closed-cell foam material
• Suitable carrier materials include materials with polar groups, by which the derivatised quaternary ammonium salt may be attached to the solid carrier by hydrogen bonding. .
• Suitable elastomers for use in the cushioning device include for example ones based on a combination of one or more alkylenes, such as ethylene, propylene and butylene, and styrene, in particular styrene ethylene butylene styrene (SBES).
• alkylenes such as ethylene, propylene and butylene
• SBES styrene ethylene butylene styrene
• the cushioning device In the cushioning devices of the present invention that are shaped to conform to affected areas to which they are applied, for example the foot or the sacrum, it is preferred that the cushioning device be made of a soft, pliable, almost viscous fluid-like plastics material.
• the cushioning device is made of a conformable gel of this type.
• the cushioning devices of the present invention that are not shaped to conform to affected areas to which they are applied, for example each side of the torso and the back, it is preferred that the cushioning device be made of a soft, pliable plastics material, but one that is not almost viscous fluid-like.
• Suitable and preferred derivatised quaternary ammonium salts in cushioning antimicrobial compositions of the invention are in general as so described hereinbefore in relation to corresponding components of absorbent antimicrobial compositions.
• One form of a cushioning device comprises
• an absorbent conformable component which comprises a substantially water- insoluble antimicrobial composition of the first aspect of the present invention, on or in a proximal face of
• a cushioning component which comprises a cushioning component, as defined herein, but optionally without an antimicrobial composition of the first aspect of the present invention.
• the two components are optionally bonded to each other.
• the cushioning device thus provides topical anti-microbial activity in contact with bodily fluid on a body surface or wound exudate, and cushioning of pressure- sensitive parts of the body, from two different components.
• the cushioning component may be unshaped, such as a layer or sheet, or one shaped to conform in use to a pressure-sensitive part of the body.
• the absorbent component which comprises a substantially water-insoluble antimicrobial composition of the first aspect of the present invention, will usually conform to, and be roughly coterminous with the cushioning component, and thus have the same or similar configurations, dimensions and shapes as the cushioning component.
• Suitable and preferred derivatised quaternary ammonium salts wherein the quaternary ammonium salt is N-substituted by a group of formula (I) and a group R 5 , as defined herein, and solid substantially water-insoluble carrier to and/or within which the derivatised quaternary ammonium salt is attached and/or dispersed, are as so described hereinbefore for respectively the absorbent component and the cushioning component.
• the device comprising the antimicrobial composition of the first aspect of the invention is in the form of an antimicrobial spraying device containing the antimicrobial composition for spraying a surface with an aerosol comprising an aqueous liquid medium comprising the antimicrobial composition.
• Such a device comprising the antimicrobial composition of the first aspect of the invention may be
• a wound care antimicrobial device for spraying the composition (which is optionally absorbent for absorbing wound exudate from a wound) onto a wound;
• a personal care antimicrobial device for spraying the composition (which is optionally absorbent for absorbing a bodily fluid from a body surface) onto a body surface.
• Either antimicrobial device for spraying the composition may be in the form of a pressurised vessel such as a can or canister with the capability of spraying the composition in the form of an aerosol comprising an aqueous liquid medium comprising the water-insoluble antimicrobial composition, typically as a suspension of a fine particulate of a substantially water-insoluble carrier to which the derivatised quaternary ammonium salt is attached.
• the carrier of the antimicrobial composition of the first aspect of the invention may not only to comprise an absorbent material but such a material which may swell in contact with water to become an elastic gel material. This may coalesce to form an integral conformable absorbent material, in the manner of a so-called plastic skin, which may be removed from the wound site in one piece, without irrigation, and with minimum pain and shedding.
• All the antimicrobial cushioning or absorbent devices, corresponding components, compositions and materials of the present invention may also comprise therapeutically active materials other than the derivatised quaternary ammonium salt.
• therapeutically active materials should be biocompatible materials which are compatible with the other device components, compositions and materials, and in particular when in a wound dressing and in direct or fluidic contact with wound exudate, preferably attached to the solid substantially water-insoluble carrier.
• Any such therapeutic agent should be pharmaceutically acceptable, and may suitably be any of the following pharmaceutically acceptable ingredients:
• emollients such as skin lipids and sterols, oils, for example lightweight oils, such as cetyl alcohol, or silicone-derived oils, such as cyclomethicone, and heavier oils, such as grape seed oil or dimethicone, and petrolatum;
• oils for example lightweight oils, such as cetyl alcohol, or silicone-derived oils, such as cyclomethicone, and heavier oils, such as grape seed oil or dimethicone, and petrolatum;
• topical analgesics such as ibuprofen, diclofenac and capsaicin; to treat pain in combination with the soothing effect of the present cushioning device (optionally in relation to cushioning devices for relieving pressure on painful arthritic joints, such as fallen arches of the foot, for longer-term pain relief);
• topical anaesthetics such as lidocaine to numb affected parts of the human or animal body
• topical antiinflammatories such as steroids, such as Cortisol;
• the present invention provides a process for producing a solid substantially water-insoluble antimicrobial composition according to the first aspect of the present invention for an antimicrobial device, which process comprises
• a first embodiment of this third aspect of the present invention provides a process for producing an absorbent antimicrobial composition according to the first aspect of the present invention for an antimicrobial device, which process comprises adding to a carrier, and/or impregnating the carrier with, the water- soluble therapeutically active derivatised quaternary ammonium salt in a fluid medium.
• the fluid is often a highly aqueous fluid, especially when the material for the carrier is a water-absorbent polymeric material that is substantially water-insoluble, as described hereinbefore in greater detail.
• a second embodiment of this third aspect of the present invention provides a process for producing a cushioning antimicrobial composition according to the first aspect of the present invention which process comprises dispersing the water-soluble therapeutically active derivatised quaternary ammonium in a, typically fluid, precursor of the carrier, followed by solidification of the precursor of the carrier to form the carrier.
• the fluid medium comprising the water-soluble therapeutically active derivatised quaternary ammonium salt is usually
• aqueous solution in which the quaternary ammonium salt is dissolved to at least 0.1 %, and up to 0.5%, for example up to 1 % w/w, usually in a highly aqueous medium as defined; or
• the aqueous solution comprising the derivatised quaternary ammonium salt is usually in a highly aqueous medium as defined. It will generally comprise at least 0.1 %, and up to 0.5%, for example up to 1 % w/w, of a surfactant to promote wetting of the carrier.
• the surfactant should promote wetting of the carrier without competing with the derivatised quaternary ammonium salt for typical sites of attachment to the solid carrier by pairing of ions of opposite charges, typically the anions of salts, such as of salified carboxylic acids.
• Favoured surfactants thus include nonionic surfactants, such as polymeric material of which the largest part (by weight) consists of homo- or copolymers of oxyolefins such as oxyethylene, oxypropylene, oxybutylene or oxy-4-methyl-l- pentene.
• polyoxyethylene alkyl ethers (Brij), for example of the formula: CH 3 -(CH 2 )io-i6-(O-C 2 H 4 ) _25-OH, such as octaethylene glycol monododecyl ether and pentaethylene glycol monododecyl ether; and polyoxypropylene glycol alkyl ethers, for example of the formula: CH 3 -(CH 2 )io-i6-(O-C 3 H6)i-25-O.
• Brij polyoxyethylene alkyl ethers
• Such non-Ionic surfactants preferably comprise residues of an oligosaccharide with alkylated hydroxyl functions, typically oligoglucoside alkyl ethers, for example decyl glucoside, dodecyl glucoside, octyl glucoside and decyl octyl glucoside (APG), often formed by an alkylation reaction between a function such as the anion of an alkali metal oxide, such as a sodium oxide group, in the oligosaccharide.
• APG decyl octyl glucoside
• a relatively volatile non-aqueous liquid in the frequently highly aqueous medium in particular in an aerosol comprising the aqueous solution.
• This should be a water-miscible non-solvent for the carrier, but a solvent for the derivatised quaternary ammonium salt and/or the cationic antimicrobial salt c), typically isopropanol or ethanol, frequently at a concentration of 1 to 10 %, such as 3 to 8 %, for example 5 to 6 % w/w, in the aqueous solution per se or in the aerosol.
• This may aid evaporation and/or to help to solubilise therapeutically active derivatised quaternary ammonium salts with more hydrophobic groups and/or steric hindrance around the nitrogen atom of the ammonium cation caused by the other substituent groups present.
• anion of such derivatised quaternary ammonium salts may alternatively or additionally, usually alternatively, be chosen to help to solubilise therapeutically active derivatised quaternary ammonium salts.
• examples of these anions include anions of an organic acid, such as hydrogen pamoate and/or pamoate.
• the carrier is of a water-absorbent material
• absorption of the fluid comprising the therapeutically is active ionic material virtually instantaneous, but depending on the particular therapeutically active material the time for the treatment process overall may suitably be 1 to 60 min, such as 2 to 45 min. 2 to 45 min. is found to be most suitable to give a more useful substrate in an economic time.
• the treatment process may often be carried out by immersing the carrier, which is or comprises a water-absorbent material, in the liquid medium comprising the water-soluble therapeutically active derivatised quaternary ammonium salt for the a suitable length of time, as above. This forms a first variant of the first embodiment of this third aspect of the present invention (a process for producing an absorbent antimicrobial composition).
• the treatment may suitably be carried out at a temperature of up to 30°C, which may suitably be 5 to 25° C, for example 10 to 20° C.
• This first variant of the first embodiment may in some cases be operated as a semi-continuous process for producing an absorbent antimicrobial composition. This may be carried out by threading a length of the carrier, which is or comprises a water-absorbent material, through rollers into and through a bath containing a solution of the derivatised quaternary ammonium salt. Excess solution is then removed, and the carrier is impregnated with the water- soluble therapeutically derivatised quaternary ammonium salt pressure by feeding the carrier through nip rollers. The carrier, loaded with the derivatised quaternary ammonium salt, is then dried, for example in an oven, and cooled, for example with a chill roller.
• the carrier is already mounted in a precursor of a wound dressing comprising the therapeutically active ionic material
• the solid substantially water-insoluble carrier is of a particularly water- absorbent and -retaining material and/or structure
• composition is to be used in a wound dressing
• ii) may swell in contact with water and/or
• ii) may become an irreversible elastic gel material
• an aerosol comprising the aqueous solution of the derivatised quaternary ammonium salt, optionally also comprising a non-aqueous liquid which is a water-miscible non-solvent for the carrier.
• the carrier is already mounted in a precursor of a wound dressing comprising the therapeutically active ionic material, it will usually not be possible for the carrier to be immersed in the liquid medium comprising the water-soluble therapeutically active derivatised quaternary ammonium salt in the treatment process without compromising the other components of the dressing.
• the substantially water-insoluble but hydrophilic absorbent material used in the carrier, and/or its form and/or structure may also have the physical property of retaining an excess of the liquid medium of this process of the first embodiment.
• the undesired excess of the aqueous medium cannot be readily be removed after direct contact with the liquid medium, for example by the carrier loaded with the therapeutic derivatised quaternary ammonium salt being left to drain.
• the composition in a wound dressing also functions as an absorbent component of the dressing.
• the material of the carrier with the above properties may also be a substantially water-insoluble superabsorbent gelling, water insoluble derivatised alginate, cellulose or chitosan and/or its form and/or structure may be a foam. If it is an open-cell foam which exhibits good absorption and retention of fluid, undesired excess of the aqueous medium cannot be readily be removed after direct contact with the liquid medium, for example by the carrier loaded with the therapeutic derivatised quaternary ammonium salt being left to drain. More importantly, it can no longer function as an absorbent in the dressing.
• the second variant of the treatment process of this first embodiment of this third aspect of the present invention third aspect of the invention should be used.
• To spray the surface of the carrier with an aerosol comprising the aqueous solution of the derivatised quaternary ammonium salt will typically take less than 10 min, although multiple spraying may be desirable, for example for absorbent fibre, often microfibre or nanofibre pads or layers as defined herein.
• the time for the treatment process overall may still suitably be 1 to 60 min, such as 2 to 45 min, to allow the relatively smaller undesired excess of the aqueous medium to drain or evaporate from the surface of the carrier.
• compositions for example for absorbent fibre, typically microfibre or nanofibre pads or layers as defined herein, it may be desirable to incorporate a relatively volatile non-aqueous liquid which is a) a water-miscible non-solvent for the carrier, but
• isopropanol or ethanol frequently at a concentration of 1 to 10 %, such as 3 to 8 %, for example 5 to 6 % w/w, to the aqueous solution in the aerosol to aid evaporation.
• the treatment may suitably be carried out at a temperature of up to 30°C, which may suitably be 5 to 25° C, for example 10 to 20° C.
• the aqueous solution optionally also comprising a volatile non-aqueous liquid.
• a liquid should be a water-miscible non-solvent for the carrier.
• the spraying may be carried out as appropriate by electrospraying, that is, by forcing the above solution through a capillary nozzle or needle tip, which may optionally be made to traverse over the carrier, and applying a large potential difference of the order of several kV to the tip relative to the carrier.
• the carrier may be mounted on a counterelectrode, as a collection target, so forming a so-called Taylor cone of the solution at the tip. Applying the large potential difference also causes charged droplets to break away from the Taylor cone of the solution at the tip, and the electric field accelerates the charged droplets to towards the collection target
• a relatively volatile nonaqueous liquid in the frequently highly aqueous medium in particular in an aerosol comprising the aqueous solution.
• a solvent for the derivatised quaternary ammonium salt typically isopropanol or ethanol, frequently at a concentration of 1 to 10 %, such as 3 to 8 %, for example 5 to 6 % w/w, in the aqueous solution per se or in the aerosol.
• the Coulomb explosion forms a fine aerosol comprising the aqueous solution of the derivatised quaternary ammonium salt, which forms a layer that comprises the derivatised quaternary ammonium salt on the target.
• the form and/or structure of the substantially water-insoluble carrier corresponds to the composition form and/or structure when it is a component of a dressing.
• the component fibres may be treated with an aqueous medium comprising the derivatised quaternary ammonium salt, left to drain and/or be air- dried, and then processed according to known methods into a wide variety of forms of the composition as a component of an antimicrobial devices, and in particular in an advanced wound dressing.
• This may be, for example in the form of a non-woven fabric comprising the treated fibres.
• Such a non-woven fabric may be produced by conventional fibre opening, web formation and needling, and may suitably have a thickness of 30 to 200g/m 2 or more.
• non-medical devices such as for the personal care sector, particularly for disposable sanitary devices such as nappies (diapers) and incontinence products.
• the devices tend to be applied to other substrates, such as underwear, and/or for other bodily fluids, such as menses or urine.
• a second embodiment of this third aspect of the present invention provides a process for producing a cushioning antimicrobial composition according to the first aspect of the present invention, which process comprises dispersing the water-soluble therapeutically active derivatised quaternary ammonium salt in a, typically fluid, precursor of the carrier, followed solidification of the precursor of the carrier, to form the cushioning antimicrobial composition or device composition of the first aspect of the present invention.
• the product of this second variant of the second process embodiment may be a cushioning device which comprises a cushioning component, but is more usually in a form which consists essentially of such a component.
• the water-soluble therapeutically active derivatised quaternary ammonium salt is dispersed in a, typically fluid, precursor of the carrier, followed solidification of the precursor of the carrier. Solidification of the precursor is often characterised by the crosslinking of a non-crosslinked, or monomeric or oligomeric precursor of the material of the cushioning device according to the present invention, often in the course of reactive injection moulding or casting.
• the cushioning device is shaped to conform in use to the body over a given pressure-sensitive area where device is needed.
• a cushioning device is often relatively thick, and may have an increased thickness at the point where it is required, for example to cushioning device the arch of the foot or where it is required to cushion the sacrum.
• the process for the preparation of the cushioning device according to the first aspect of the present invention is then characterised by reactive injection moulding, for example of a room-temperature curing fluid precursor system.
• the mould into which the fluid precursor system is injected typically has inner faces that are shaped to conform to the proximal face and the opposite outer face of the desired form of the cushioning device, and is often in two cooperating parts.
• the cushioning device is not shaped to conform in use to the body over a given pressure-sensitive area where cushioning is needed, the cushioning device is often relatively thin, and may have an essentially constant thickness.
• the process for the preparation of the cushioning device according to the first aspect of the present invention is then characterised by reactive casting, for example of a room-temperature curing fluid precursor system.
• the platen onto which the fluid precursor system is cast typically has a flat face with a raised periphery or other appropriate means for containing the fluid precursor system shaped to conform to the desired form of the cushioning device.
• the invention provides a method of treatment or prophylaxis of microbial infections using an antimicrobial composition according to the first aspect of the present invention.
• a method of treatment or prophylaxis of microbial infections and any underlying pathologies in wound precursors and wounds comprising administering a therapeutically effective amount of a composition according to the first aspect of the present invention to a wound or wound precursor.
• a method of treatment or prophylaxis of microbial infections and any underlying pathologies in wound precursors and wounds comprising administering a therapeutically effective amount of a composition according to the first aspect of the present invention to a wound or wound precursor.
• This comprises applying an absorbent medical device, which is a wound dressing, comprising a therapeutically effective amount of a composition according to the first aspect of the present invention to a wound or wound precursor.
• Such a dressing can be easily applied to treat a wound on a human or animal body; including an acute wound, for example a surgical wound; a chronic wound, for example a diabetic ulcer or a venous leg ulcer; or a burn.
• an acute wound for example a surgical wound
• a chronic wound for example a diabetic ulcer or a venous leg ulcer
• a burn for example a burn.
• the dressing may be used as appropriate in a wound that extends to at least the epidermis of the animal's skin, in a wound that extends to the dermis or the subcutaneous fat region of the animal's skin, in a wound that extends into the musculature of the animal, or in a wound that extends into the viscera of the animal.
• a method of treatment or prophylaxis of a pressure-sensitive part of the body of a patient at risk of developing wound precursors and/or wounds comprising applying a medical device, which is a cushioning device to the part of the body at risk.
• a medical device which is a cushioning device to the part of the body at risk.
• Such a cushioning device of the present invention as defined can be easily applied to patients who have, or are at substantial risk of developing, wound precursors include, for example those with arthritis, diabetes, cardiovascular conditions or paralysis.
• the cushioning, medical device relieves the pressure on the skin of the patient, and makes a water-insoluble form of a quaternary ammonium salt available to the skin and/or the tissue underlying it, to combat any microbial infections and any underlying pathologies in any wound. .
• a medical device such as a wound dressing
• other medical devices of the first aspect of the invention tend to be applied to other parts of the body and/or for other bodily fluids.
• non-medical devices such as for the personal care sector, particularly for a disposable sanitary device, such as a nappy (diaper), a disposable nappy or training pants, a feminine care product, for example, a tampon, a sanitary towel, or a napkin or a pant liner, or an incontinence product.
• the devices may be applied to other substrates, such as underwear, and/or for other bodily fluids, such as menses or urine.
• a method of removal of bodily fluid (excluding wound exudate) from a body surface (including the skin and internal mucosa) of a human or animal comprising applying a non-medical absorbent device which is a personal care device, to the body surface.
• This example demonstrates the first variant of the process for making an absorbent water-insoluble composition with a derivatised quaternary ammonium salt comprised in a non-woven fabric absorbent material, for use as an absorbent component of an antimicrobial medical or non-medical device.
• a Werner Mathis AG coater was set up.
• a 20m roll of spunbond polyester material was placed on one side of the machine, and was threaded at a speed of 1 .5m/min through a bath containing a solution of the derivatised quaternary ammonium salt, N,N-dimethyl-N-octadecyl-N-2-(trimethoxysilyl)propyl- ammonium chloride (0.2% w/w solution) and a decyl octyl oligoglucoside ether surfactant (APG) (0.2% w/w solution) the remainder being deionised water.
• APG decyl octyl oligoglucoside ether surfactant
• the material was then fed through nip rollers exerting a pressure of 1 .25 bar to remove excess solution, then fed into a first oven at 100° C and a second oven also at 100° C to dry the material.
• the material loaded with the derivatised quaternary ammonium salt then left the oven, passed over a chill roller (to remove residual heat) and was batched up.
• the width of material entering the machine was 20.5cm and leaving the machine was 18cm.
• the shrinkage was likely to do with drying and stretching.
• N,N-dipropyl-N-octadecyl-N-2-(trimethoxysilyl)propylammonium acetate N,N-dimethyl-N-octadecyl-N-2-(trimethoxysilyl)propylammonium benzoate, N,N-dipropyl-N-octadecyl-N-2-(trimethoxysilyl)propylammonium hydrogen tartrate,
• quaternary ammonium salt attached to a solid carrier which is an alginate, cellulose, carboxymethylcellulose, chitosan or carboxymethyl- chitosan; with optionally salified carboxylic acid residues.
• This example demonstrates a second variant of the process for making an absorbent water-insoluble composition with a derivatised quaternary ammonium salt comprised in a polyester open-cell foam which exhibits good absorption and retention of fluid.
• the surface of a 5cm x 5cm piece of the open-cell foam is sprayed with an aerosol comprising an aqueous solution of the derivatised quaternary ammonium salt, N,N-dimethyl-N-octadecyl-N-2-(trimethoxysilyl)propylammonium chloride (0.2% w/w solution) and a decyl octyl oligoglucoside ether surfactant (0.2% w/w solution) the remainder being deionised water.
• the foam carrier loaded with the derivatised quaternary ammonium salt is left to allow the relatively small undesired excess of the aqueous medium to drain or evaporate from the surface of the carrier. It is then again sprayed with the aerosol comprising the aqueous solution of the derivatised quaternary ammonium salt, and then placed in a first oven at 100° C and a second oven also at 100° C to dry the material.
• a solid substantially water-insoluble carrier which is a polyurethane, copoly(etherester), polyalkylene, polyamide, polycarbonate, poly(iminocarbonate) or polyorthoesters foam.
• the antimicrobial activity and the degree of release by water of a derivatised quaternary ammonium salt from the composition of Example 1 were determined as follows:
• compositions had good antimicrobial activity in contact with the bacterial culture, and exhibit a surprising and advantageously negligible degree of release by water of the derivatised quaternary ammonium salt.

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• 2012
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