WO2012171920A1 - Dispositif de traitement - Google Patents

Dispositif de traitement Download PDF

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Publication number
WO2012171920A1
WO2012171920A1 PCT/EP2012/061122 EP2012061122W WO2012171920A1 WO 2012171920 A1 WO2012171920 A1 WO 2012171920A1 EP 2012061122 W EP2012061122 W EP 2012061122W WO 2012171920 A1 WO2012171920 A1 WO 2012171920A1
Authority
WO
WIPO (PCT)
Prior art keywords
response device
treatment
microbe
active response
substance
Prior art date
Application number
PCT/EP2012/061122
Other languages
English (en)
Inventor
Christian Stephenson
Original Assignee
Lantor (Uk) Limited
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 Lantor (Uk) Limited filed Critical Lantor (Uk) Limited
Publication of WO2012171920A1 publication Critical patent/WO2012171920A1/fr

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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
    • A61L15/42—Use of materials characterised by their function or physical properties
    • A61L15/44—Medicaments
    • 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
    • A61L15/56—Wetness-indicators or colourants
    • 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
    • A61F13/00051—Accessories for dressings
    • A61F13/00063—Accessories for dressings comprising medicaments or additives, e.g. odor control, PH control, debriding, antimicrobic

Definitions

  • the present invention provides an active response device for the in situ combating of a substance or a microbe at a location, and methods for its use and construction.
  • a dressing applied over the wound with the purpose of excluding microbes may not exclude all microbes, and many bacteria can grow within a host, e.g. in a wound, without harming it, until they reach a certain concentration, at which they sense each other's presence (so-called quorum sensing). Only then do they become aggressive, they multiply, and their numbers become sufficient to overcome the host's immune system and form a biofilm, leading to infection and/or disease.
  • infection can be seriously detrimental to the patient; and may impair wound healing and in extreme cases result in local infection and potentially septicaemia.
  • antimicrobial treatments are often administered to wounds prophylactically, but also indiscriminately.
  • a disadvantage of such a method of treatment is that significant quantities of antimicrobials may be wasted.
  • Another disadvantage is that unnecessary exposure of microbes to antimicrobials can unnecessarily activate the evolutionary mechanisms that select for resistant strains and could potentially lead to the development of antimicrobial-resistant strains of microbes.
  • Today, about 70% of the bacteria that cause infections are resistant to at least one of the drugs most commonly used for treatment. Some organisms are resistant to all approved antibiotics and can only be treated with experimental and potentially toxic drugs.
  • a) applies an antimicrobial or other active agent to a location potentially susceptible to infection only when the concentration of a substance or microbe at a particular location reaches a predetermined concentration, for example a level at which infection is likely to develop, and/or
  • an active response device suitable for detecting and combating a substance or a microbe at a location, which active response device comprises:
  • the treatment integer (b) is initially shielded from the substance or microbe by the sacrificial layer (a).
  • the substance or microbe will act on the sacrificial layer between it and the treatment integer to reduce its thickness or remove it at least in part and/or to change its chemical composition and/or structure, for example it has become porous and permeable to the treatment material, thus allowing the treatment integer to release the treatment material to the location.
  • the thickness and/or change in the chemical composition and/or structure of the sacrificial layer between the treatment integer and the location determines the time until it allows release of the substance.
  • the location at which the treatment material is to be released to the location may be a human or animal location, particularly on or in a living human or animal body, for example a wound; a foodstuff or a personal care product; a domestic location, e.g. a kitchen or bathroom; or an industrial location, e.g. a laboratory location, such as a steriliser or machinery or a surface involved in the release of pharmaceutical products, personal care or food products.
  • the substance may be for example a chemical substance in a personal care product or a foodstuff, which could be present at a concentration at which the personal care product or foodstuff is dangerous to apply to the body or to ingest, as appropriate.
  • the substance may be a substance associated with a microbe in any type of location.
  • the substance may be, for example, a microbial product, a part of the microbial cell contents, or where the location is a living human or animal body a substance associated with the body's response to a microbe.
  • the presence of the substance is indicative of the presence of the microbe and degrades the sacrificial layer (a), and causes the release of the treatment material which combats the microbe by the treatment integer.
  • the microbe could be present in a personal care product or a foodstuff at a concentration at which the personal care product or foodstuff is dangerous to apply to the body or to ingest, as appropriate. Where the location is a wound in a human or animal, the microbe could be present at a level at which infection, disease or other pathological condition might develop.
  • the device monitors, detects, and may be adapted to indicate and/or draw attention to, chemical and/or microbial contamination, and prevents its further spread or increase to an unacceptable level at the location or to other food or products.
  • the location is a human or animal location, particularly on or in a living human or animal body, for example a wound
  • initial release of the treatment material will combat the contamination or microbial bioburden at the location
  • the device for example in an antimicrobial wound dressing, may be adapted to release sufficient treatment material to eliminate microbial contamination, and/or prevent its reoccurrence.
  • the device (again conveniently in a wound dressing) may be applied to the wound and be used to monitor the treatment by monitoring any reoccurrence of the substance and hence of the microbe. It will release the treatment material as and when the concentration of the microbe at the wound location reaches a predetermined concentration, for example a dangerous level at which infection, disease or other pathological condition could reoccur, and there is a risk of the patient failing to recover or relapsing.
  • a predetermined concentration for example a dangerous level at which infection, disease or other pathological condition could reoccur, and there is a risk of the patient failing to recover or relapsing.
  • the treatment integer may be a sustained release body, which once activated continues to release the treatment material at a concentration in the wound in a human or animal which combats the redevelopment of a dangerous and/or infectious level of the microbe at the location reaches over a sustained time period.
  • a main advantage of the invention is that the device will release the treatment material only when the concentration of a substance or microbe at a particular location has reached a predetermined concentration, for example a dangerous level.
  • the invention therefore provides a timelier, more relevant and less indiscriminate treatment than hitherto.
  • a further advantage of the active response device according to the invention is that it may combat microbial activity throughout a required time period.
  • any microbe at the location may be, for example, a micro-organism, e.g. a bacterium, virus, mould, yeast, protozoon or fungus, including pathogenic and non-pathogenic micro-organisms.
  • the substance may be for example a substance associated with a microbe, and degradation of the sacrificial layer (a) by the substance causes release of a treatment material by the treatment integer.
  • the substance may be, for example, a microbial product, a part of the microbial cell contents, or a substance associated with the location's response to a microbe where the location is a living human or animal body.
  • a microbial product as a substance include an enzyme, for example an oxidase, lipase, tryptophanase, beta-lactamase, beta-lactamase inhibitor, esterase, dehydrogenase, kinase, hydrolase, protease, nuclease, phosphatase, decarboxylase, and/or carboxylase.
  • the microbial product may also be a naturally occurring organic phosphate such as adenosine triphosphate (ATP), a pyridine nucleotide such as nicotinamide adenine dinucleotide (NADH) or a flavin such as flavin adenine dinucleotide (FADH).
  • ATP adenosine triphosphate
  • NADH nicotinamide adenine dinucleotide
  • FADH flavin
  • a substance associated with the location's response to a microbe where the location is a living human or animal body
  • the treatment material may, as appropriate to the microbes present at or in the wound, comprise one or more antibiotic or antimicrobial products in particular for combating pathogenic micro-organisms. .
  • Such products include a topical antibacterial, which may be a bactericidal agent or a bacteriostatic agent.
  • Suitable such substances include a topical or systemic beta-lactam antibacterial, such as a natural or semi-synthetic penicillin, a cephalosporin or a carbapenem.
  • Other suitable substances include natural antibacterials, such as aminoglycosides, synthetic antibacterials, such as sulphonamides, quinolones, polyhexamethylene biguanide (PHMB) hydrochloride, and oxazolidinones, and inorganic bactericides, such as nitric oxide, and others well-known to the skilled person.
  • Such products also include a topical or systemic antiviral, such as idoxuridine, trifluridine, and aciclovir
  • a topical or systemic antifungal or anytimycotic Such products further include a topical or systemic antifungal or anytimycotic. Suitable such substances include imidazole, triazole and thiazole antifungals, allylamine antifungals, and echinocandins.
  • the substance at the location may be for example a substance associated with a microbe.
  • Such substances include an enzyme, for example an oxidase, lipase, tryptophanase, a (generally mycotic) beta-lactamase, (generally bacterial) beta-lactamase inhibitor, esterase, dehydrogenase, kinase, hydrolase, protease, nuclease, phosphatase, decarboxylase, and/or carboxylase.
  • the treatment material may, as appropriate to the enzymes present at or in the wound, comprise one or more enzyme inhibitors in particular for combating enzymes from pathogenic micro-organisms.
  • Such products include a topical or systemic inhibitor for oxidase, lipase, tryptophanase, a (generally mycotic) beta-lactamase, (generally bacterial) beta-lactamase inhibitor, esterase, dehydrogenase, kinase, hydrolase, protease, nuclease, phosphatase, decarboxylase, and/or carboxylase.
  • the treatment material is released to the location from the treatment integer whenever the contamination or microbial bioburden within the location reaches a predetermined concentration, for example a dangerous level.
  • the location at which the active response device will be used, and where the substance or microbe to be released to the location is present location is often for example a body tissue, foodstuff or personal care product, so that the active response device is often for use in an environment which is a fluid, more often an aqueous fluid.
  • the treatment material should usually be at least partially water-soluble or water-miscible.
  • the sacrificial layer (a) which initially lies between the treatment integer (b) and the substance or microbe at the location preferably comprises a solid, water-insoluble, water-impervious material which is also substantially impermeable to the treatment material.
  • the treatment integer (b) may comprise the treatment material, or it may consist essentially of the treatment material.
  • the treatment material may be a solid, liquid or gas. Where the treatment material is a solid, it may as appropriate be, or be comprised in, the treatment integer (b) in the form of one or more flexible films, layers or membranes, having one or more plies.
  • the treatment material may be comprised in a treatment integer which is in the form of one or more absorbent sheets, films, layers or membranes, or pads, cushions or wadding formed from foam or woven or non- woven fibres, strands, threads or yarns, and having one or more plies, of a biocompatible material which is insoluble in the location environment, usually water-insoluble, and often hydrophilic.
  • a treatment integer may be a sustained release body, which once activated continues to release the treatment material at a location, for example a wound in a human or animal, which combats the redevelopment of a dangerous and/or infectious level of the microbe at the location reaches over a sustained time period.
  • the treatment material is then often present in the form of an absorbed solution from which the solvent has optionally been evaporated.
  • Suitable absorbent materials include alginate, and cellulosic fibres, such as in an absorbent paper, cotton gauze or lint, or viscose.
  • the treatment integer which is adapted to release the treatment material on contact with the location is initially shielded from the substance or microbe in the location by the sacrificial layer (a) suitably inter alia in the form of one or more continuous sheets, films, layers or membranes, which is/are at least coterminous with the treatment integer.
  • the sacrificial layer (a) may be in the form of a layer between a face of the treatment integer and the location.
  • the treatment integer may alternatively be sandwiched by two parts of the layer (a), or the latter may be in a form which extends on all sides of the treatment integer, so that the latter is embedded, encapsulated or enclosed in, or sandwiched by an integral layer (a).
  • the treatment material is a solid, it may more often be comprised in a treatment integer in the form of a fluid solid material, for example a particulate, such as a granulate or fine particles, for example powder or dust.
  • a treatment integer may be a sustained release body.
  • the treatment material may be comprised in a treatment integer which is in the form of an absorbent particulate.
  • the treatment material is then often present in the form of an absorbed solution from which the solvent has optionally been evaporated.
  • Suitable absorbent materials include cellulosic particles, such as ones of carboxymethylcellulose, chitosan, chitosan derivatives, such as carboxymethylchitosan and salts thereof, and alginate
  • the treatment integer may be initially shielded from the substance or microbe in the location by the sacrificial layer (a) suitably inter alia in the form of one or more continuous sheets, films, layers or membranes, which is/are at least coterminous with the treatment integer.
  • the sacrificial layer (a) may be in the form of a layer between the treatment integer and the location which extends on all sides of the treatment integer and is attached to another (inert) layer, or the treatment integer may be sandwiched by two parts of the layer (a) which extend on all sides of the treatment integer, so that the latter is encapsulated or enclosed at least in part by the layer (a).
  • the sacrificial layer may be formed in situ on the treatment integer by casting, or dip, jet, mist or spray coating a polymer or compatible polymers to a suitable thickness onto the relevant surfaces of the treatment integer.
  • the layer (a) is often in the form of a (preferably continuous) coating, covering or film on substantially each particle, encapsulating or enclosing the treatment material particle.
  • the sacrificial layer may be formed in situ on the treatment integer by, for example pan coating or air-suspension coating with a jet, mist or spray of a solution or melt of the sacrificial layer material, often a compatible biopolymer to a suitable thickness onto the particles of the treatment material. It may also be formed by spray-drying of the treatment material dissolved or suspended in a melt or solution of the sacrificial layer material, often a compatible biopolymer. Where the treatment material is a liquid, it may as appropriate be, or be comprised in, the treatment integer (b) in the form of one or more bodies of liquid contained in one or more flexible films, layers or membranes, having one or more plies.
  • the treatment material may be comprised in a treatment integer which is in the form of one or more absorbent sheets, films, layers or membranes, or pads, cushions or wadding formed from foam or woven or non- woven fibres, strands, threads or yarns, and having one or more plies, of a biocompatible material which is insoluble in the location environment, usually water-insoluble. It is often present in the form of an absorbed liquid. Suitable absorbent materials include alginate, and cellulosic fibres, viscose and cotton.
  • the treatment integer which is adapted to release the treatment material on contact with the location is initially shielded from the substance or microbe in the location by the sacrificial layer (a) suitably inter alia in the form of one or more continuous sheets, films, layers or membranes, which is/are at least coterminous with the treatment integer.
  • the sacrificial layer (a) may be in the form of a layer between a face of the treatment integer and the location.
  • the treatment integer may alternatively be sandwiched by two parts of the layer (a), or the latter may be in a form which extends on all sides of the treatment integer, so that the latter is embedded, encapsulated or enclosed in, or sandwiched by an integral layer (a).
  • the treatment material is a liquid
  • it may often be comprised in a treatment integer in the form of a fluid solid material, for example a particulate, such as a granulate or fine particles, for example powder or dust.
  • a treatment integer may be a sustained release body.
  • the treatment material is then often present in the form of an absorbed liquid.
  • Suitable absorbent materials include cellulosic particles, such as ones of carboxymethylcellulose, chitosan, chitosan derivatives, such as carboxymethylchitosan and salts thereof, alginate, PLGA, and PEG.
  • the treatment integer may be initially shielded from the substance or microbe in the location by the sacrificial layer (a) suitably inter alia in the form of one or more continuous sheets, films, layers or membranes, which is/are at least coterminous with the treatment integer.
  • the sacrificial layer (a) may be in the form of a layer between the treatment integer and the location which extends on all sides of the treatment integer and is attached to another (inert) layer.
  • the treatment integer may be sandwiched by two parts of the layer (a) which extend on all sides of the treatment integer, so that the latter is encapsulated or enclosed at least in part by the layer (a).
  • the sacrificial layer may be formed in situ on the treatment integer by pan coating or air-suspension coating with a jet, mist or spray of a solution or melt of the sacrificial layer material, often a compatible biopolymer to a suitable thickness onto the particles of the treatment material. It may also be formed by spray-drying of the treatment material dissolved or suspended in a melt or solution of the sacrificial layer material, often a compatible biopolymer.
  • the treatment material is a liquid
  • it may be present in the form of a particulate, such as a granulate or fine particles, comprising liquid, particulate treatment material cores encapsulated or enclosed by the layer (a) in the form of a (preferably continuous) coating, covering or film on substantially each particle.
  • the encapsulating sacrificial layer may be formed in situ on the treatment material particles by, for example by centrifugal co-extrusion from a rotating or vibrational nozzle extrusion head containing concentric nozzles of a jet of core liquid surrounded by a sheath of layer (a) solution or melt.
  • the treatment material is a gas
  • the treatment integer (b) in the form of one or more bodies of free gas.
  • the treatment material may be comprised as a gaseous ab- and/or adsorbate in a treatment integer which is in the form of one or more absorbent sheets, films, layers or membranes, or pads, cushions or wadding formed from foam or woven or non-woven fibres, strands, threads or yarns, and having one or more plies.
  • Suitable absorbent materials include cellulosic fibres, alginate and chitosan, chitosan derivatives, such as carboxymethylchitosan and salts thereof
  • the treatment integer which is adapted to release the treatment material on contact with the location is initially shielded from the substance or microbe in the location by the sacrificial layer (a) suitably inter alia in the form of one or more continuous sheets, films, layers or membranes, which is/are at least coterminous with the treatment integer.
  • the sacrificial layer (a) may be in the form of a layer between a face of the treatment integer and the location.
  • the treatment integer may alternatively be sandwiched by two parts of the layer (a), or the latter may be in a form which extends on all sides of the treatment integer, so that the latter is embedded, encapsulated or enclosed in, or sandwiched by an integral layer (a).
  • the treatment material is a gas
  • it may more often be comprised as a gaseous absorbate and/or adsorbate in a treatment integer in the form of a fluid solid material, for example a particulate, such as a granulate or fine particles, for example powder or dust.
  • a treatment integer may be a sustained release body.
  • the treatment material may be comprised in a treatment integer which is in the form of an absorbent particulate.
  • absorbents are generally porous and permeable to the treatment material, thus allowing the treatment integer to absorb and/or adsorb the treatment material gas.
  • the structure of the ab/adsorbent material, including the cross-sectional area and patterns of holes, channels or pores inside the treatment integer should be chosen with regard to the molecular dimensions of the desired gas.
  • the chemical composition of the treatment integer (b) ab/adsorbent should be chosen with regard to chemical nature of the desired gas, such that binding of the gas to the ab/adsorbent is possible, but sufficiently labile to allow the treatment integer to release the treatment material to the location when in contact with the components of the location environment (often a fluid, more often an aqueous fluid).
  • the treatment material is nitric oxide
  • it may often be comprised in a treatment integer in the form of a fluid zeolite particulate
  • suitable zeolites for the treatment integer include zeolites and ion-exchanged zeolites.
  • the nitric oxide is released from a zeolite on contact with aqueous media, for example wound fluid.
  • the structure and composition of the zeolite material may be tailored to control the amount of nitric oxide loaded into the zeolite and/or the rate at which the nitric oxide is released from the zeolite.
  • the pores and channels in a zeolite structure may be defined by the size of the pore or channel openings.
  • the zeolite with the structure LTA has openings defined by 8 pore tetrahedral units (i. e. a ring of 8Si/AI atoms and 8 oxygen atoms).
  • Zeolite MFI has a larger ring opening defined by 10 tetrahedral units, and FAU by an even larger pore opening of 12 tetrahedral units.
  • the dimensionality of the pores can also differ between zeolite structures. For example, some zeolites have channels that run in only one direction (one dimensional channel systems) while others have systems of interacting channels in two or three dimensions (2- dimensional and 3-dimensional channel systems).
  • the size, shape and dimensionality of zeolites may affect the rates of diffusion and adsorption/desorption of NO, and may be used to control the rate of release of NO from the zeolite in a particular application.
  • Each different cation in a zeolite may have a different affinity for NO and changing the cations present in the zeolite structure may be used to control the release of NO.
  • Such manipulation of the zeolite composition can affect the rate at which the nitric oxide is released from the zeolite.
  • a sodium-loaded zeolite may bind nitric oxide less strongly than an iron-loaded zeolite to release the nitric oxide more rapidly.
  • a mixed sodium/iron zeolite may release nitric oxide at a different rate to either a sodium-loaded zeolite or an iron-loaded zeolite, and such release of nitric oxide may present a different rate profile.
  • the choice of zeolite structure and composition can be used to vary the loading and release rate of nitric oxide.
  • Suitable absorbent materials for other absorbed gaseous treatment materials present in an absorbent particulate will be well-known to the skilled person, but include zeolite particles, as well as for instance clay minerals.
  • the treatment integer may be initially shielded from the substance or microbe in the location by the sacrificial layer (a) suitably inter alia in the form of one or more continuous sheets, films, layers or membranes. These are usually at least coterminous with the treatment integer.
  • the sacrificial layer (a) may be in the form of a layer between the treatment integer and the location which extends on all sides of the treatment integer and is attached to another (inert) layer, or the treatment integer may be sandwiched by two parts of the layer (a) which extend on all sides of the treatment integer, so that the latter is encapsulated or enclosed at least in part by the layer (a).
  • the layer (a) is often in the form of a (preferably continuous) coating, covering or film on substantially each particle, encapsulating or enclosing the treatment material particle.
  • the sacrificial layer may be formed in situ on the treatment integer by, for example pan coating or air-suspension coating with a jet, mist or spray of a solution or melt of the sacrificial layer material, often a compatible biopolymer to a suitable thickness onto the particles of the treatment material. It may also be formed by spray-drying of the treatment material dissolved or suspended in a melt or solution of the sacrificial layer material, often a compatible biopolymer.
  • the treatment integer may be in the form of any of the forgoing particulates, such as a granulate or fine particles, comprising solid or liquid treatment material cores encapsulated or enclosed by the layer (a) in the form of a (preferably continuous) coating, covering or film on substantially each particle.
  • a gaseous absorbate and/or adsorbate in a treatment integer in the form of a fluid solid material for example a particulate, such as a granulate or fine particles encapsulated or enclosed by the layer (a) in the form of a (preferably continuous) coating, covering or film on substantially each particle.
  • such fluid treatment integers must be held in fluidic communication with and/or in contact with the location. This may be effected with a retaining layer which is at least partially permeable to the substance or microbe and the location environment (often a fluid, more often an aqueous fluid). It will be understood that to do so, the treatment integer must have channels leading between the location to the sacrificial layer that provide pathways that facilitate diffusion of the substance or microbe, and optionally the components of the location environment through the retaining layer.
  • the cross-sectional area of the channels through the layer should be chosen with regard to the desired time in which a desired concentration of a substance or microbe is to be released to the location. They should also be chosen such that the diffusion of the substance or microbe through the retaining layer does not become a rate-limiting step.
  • the retaining layer may be in the form of one or more sheets, films, layers or membranes, preferably formed as a membrane in the form of a net or netting, mesh, web, grid or lattice, or other arrangement or pattern of apertures, holes, openings, perforations, slits or slots, that provide pathways that facilitate diffusion of the substance or microbe, and the location environment through the retaining layer.
  • Such a retaining layer may be formed, as appropriate to the application for which the active response device is intended, by casting, or jet, mist or spray coating a relevant polymer or compatible polymers to a suitable thickness onto the surface of a correspondingly embossed former of e.g. stainless steel, as appropriate.
  • slits or slots that provide pathways that facilitate diffusion of the substance or microbe, and optionally the components of the location environment which are fluid, through the retaining layer may be formed by slitting or slicing, or similarly cutting or incising a precursor of the treatment integer.
  • the slit layer, or a correspondingly scored layer may additionally be stretched conventionally to form a net or netting, mesh, web or other like arrangement or pattern of apertures, holes, openings or perforations.
  • the cross-sectional area of the channels through the layer which are in the form of apertures, holes, openings, perforations, slits or slots, in such net or netting, mesh, web, grid or lattice, or other arrangement or pattern, may suitably be 30 micron to 5 mm gauge, for example 65 micron to 1 mm, such 100 to 150 micron gauge.
  • the layer may suitably be a solid, water-insoluble, open-cell polymer foam layer.
  • the pathways that facilitate diffusion of the substance or microbe, and optionally the components of the location environment which are fluid, through the retaining layer may be provided by interconnecting transmitting channels, which pass through the layer and are conduits or pores of smaller cross-sectional area, which may suitably be 10 micron to 1 .5 mm gauge, for example 30 to 500 micron, such as 30 to 150 micron gauge.
  • Such channels may be created by first mixing a polymer and a channelling agent, heating the mixture above the polymer's melting point and then allowing it to cool, and then removing the channelling agent.
  • the resultant polymer matrix contains a network of interconnecting channels through it.
  • Suitable channelling agents include polyglycol, polyethylene glycol, EVOH, or glycerin.
  • the above materials are in incompatible with the other polymer material(s) comprised in the layer (b).
  • Such channels through the layer are formed by phase separation of the layer polymer(s) and channelling agent on cooling, and the latter materials may be removed from the matrix of the layer (b) by leaching or by other methods which will be well-known to the skilled person.
  • the retaining layer may be in the form of one or more woven or non-woven textile fabric cloths, pads, cushions or wadding formed from fibres, strands, threads or yarns, and having one or more plies.
  • the spaces between the fibres, strands, threads or yarns form channels leading and the location to the sacrificial layer that provide pathways that facilitate diffusion of the substance or microbe through the polymer layer.
  • They may suitably be of an cross-dimension equivalent to that noted above for a retaining layer which is a membrane in the form of a net or netting, mesh, web or other like arrangement or pattern of apertures, holes, openings or perforations.
  • the channels that facilitate diffusion of the substance or microbe through the retaining layer may beneficially act as wicking means.
  • wicking means facilitates diffusion of the substance or microbe, and optionally the components of the location environment which are fluid, more often an aqueous fluid, through the retaining layer between the location and the sacrificial layer, particularly if the fabric comprises a polymer with a hydrophilic component.
  • the retaining layer (b) at least initially lies between the substance or microbe and at least part of the sacrificial layer (a) at the location at which the active response device will be used. It is in fluidic communication and/or adjacent to, or preferably in contact with the sacrificial layer.
  • thermoplastic materials such as polypropylene and polyethylene (including high-density polypropylene and polyethylene, ABS, polystyrene, polycarbonate, Nylon, PVC, thermoplastic elastomers, polyester, PVDF, nitrocellulose, polysulphone, cellulose acetate, nylon, a polymer with a hydrophilic component, and/or thermoset plastics.
  • the above materials are compatible with water-insoluble biopolymers which may be used in layer (a) such as chitosan and derivatives thereof, such as amine salts thereof and alkalised and/or optionally salified organic and inorganic acyloxyalkylchitosans and polyester amide.
  • the retaining layer may be in the form of a layer between the particulate treatment integer and the location.
  • the treatment integer may alternatively be sandwiched by two parts of the layer, or the latter may be in a form which extends on all sides of the treatment integer, so that the integer is enclosed in an integral retaining layer.
  • the retaining layer may be (preferably permanently) attached to an inert backing layer. They may be joined to each other by adhering, moulding, welding or bonding. Less preferably, the layers of the active response device may form separate integers, demountably attached to each other within an active response device according to the invention.
  • a sacrificial layer which is susceptible to degradation by a substance or microbe initially
  • the treatment integer (b) is initially shielded from the substance or microbe by the sacrificial layer (a).
  • the sacrificial layer (a) preferably comprises a solid, water-insoluble, water- impervious biopolymer which is degradable by the microbe or a substance associated with the microbe, in particular in the case of a microbe, for example where the location is a wound in a human or animal, and where the release occurs at a level at which infection might develop.
  • suitable solid, water-insoluble, water-impervious biopolymers for use in layer (a) include chitin, chitosan and derivatives thereof, such as amine salts thereof and alkalised and/or optionally salified organic and inorganic acyloxyalkylchitosans, keratan sulphate, hyaluronic acid, chondroitin, polyhydroxybutyrate, polyester amides, polytrimethylene succinate, albumin crosslinked polyvinylpyrrolidone and dextran.
  • the insoluble biocompatible material(s) comprised in the sacrificial layer are also compatible with the insoluble polymers which may be used in any retaining layer.
  • chitosan and derivatives thereof such as amine salts thereof and alkalised and/or optionally salified organic and inorganic acyloxyalkylchitosans
  • polyester amide layer (a) materials are compatible with possible retaining layer materials such as polypropylene and polyethylene (including high-density polypropylene and polyethylene and ABS. They are also compatible with polystyrene, polycarbonate, PVC, thermoplastic elastomers, polyester, PVDF, nitrocellulose, polysulphone, cellulose acetate and polyamides. Other such materials compatible with layer (a) materials will be well-known to the skilled person.
  • microbes to be combated at the location and of substances associated with microbes, where degradation of the sacrificial layer (a) by the substance causes release of a treatment material by the treatment integer, are described above.
  • Examples of a microbial product as such a substance include an enzyme, particularly, an oxidase, lipase, tryptophanase, beta-lactamase, beta-lactamase inhibitor, esterase, dehydrogenase, kinase, hydrolase, protease, nuclease, phosphatase, decarboxylase, and/or carboxylase.
  • an enzyme particularly, an oxidase, lipase, tryptophanase, beta-lactamase, beta-lactamase inhibitor, esterase, dehydrogenase, kinase, hydrolase, protease, nuclease, phosphatase, decarboxylase, and/or carboxylase.
  • Examples of a substance associated with the location's response to a microbe where the location is a living human or animal body include an immune cell product, or an enzyme such as lysozyme or a protease.
  • the substance associated with the microbe may be one or more of the following substances, and suitable corresponding materials comprised in the layer (a) may be one or more of the following solid, water- insoluble water-impervious biopolymers: Substance Biopolymer
  • the substance associated with the microbe may be one or more of the following substances, and suitable corresponding materials comprised in the layer (a) may be one or more of the following solid, water-insoluble, water- impervious biopolymers:
  • pepsin albumin crosslinked polyvinylpyrrolidone dextranase d extra n
  • the substance or microbe will act on the sacrificial layer between it and the treatment integer
  • the release time is determined by the molar concentration of the substance or microbe and the molar rate of degradation of the sacrificial layer by the substance or microbe.
  • the thickness and/or change in the chemical composition and/or structure of the sacrificial layer between the treatment integer and the location determine the molar rate of degradation, and may be adapted to for a desired release time.
  • the release time will be long in comparison to the time where the concentration is larger or the molar rate is greater.
  • the rate of degradation of the sacrificial layer will increase.
  • the thickness of layer (a) and the material used to make it are preferably chosen according to the location at which the active response device is to be used. For example, if the active response device is designed to combat a microbe, the sacrificial layer (a) is structured such that the sacrificial layer allows the release of a treatment material before the concentration of the microbe reaches a dangerous level.
  • Suitable structures for the sacrificial layer in the present device are described hereinbefore.
  • the release time may of course be adjusted inter alia by adjusting the thickness of the sacrificial layer (a).
  • the relevant thickness of layer (a) can easily be determined by a person of skill in the art when the location at which the active response device is to be used and the type of substance or microbe which is likely to be present are known.
  • the sacrificial layer is in the form of a membrane, its total thickness may be 0.1 mm - 2mm, for example 0.3 to 1 .5 mm, such as 0.5 to 1 mm in thickness, depending on the material used to make it, and the substance or microbe which degrades it.
  • the release time may of course also be adjusted for a given substance or microbe inter alia by adjusting the material of the sacrificial layer (a).
  • the substance associated with the microbe may be one or more of the following substances, and suitable corresponding materials comprised in the layer (a) may be one or more of the following solid, water- insoluble water-impervious biopolymers: Substance Biopolymer
  • Chitosan is derived from the deacetylation of chitin, the derived product used generally being chitosan which is >50% deacetylated chitin. 50% and higher levels of de-acetylation produce a material having the required mechanical and biochemical characteristics, namely a material which is strong enough to handle but which will degrade in the presence of lysozyme. We have found that the higher the degree of deacetylation of the chitosan, the more slowly the product is dissolved by lysozyme.
  • the active response device may be for example in an antimicrobial wound dressing being used to release the treatment material when the concentration of a substance or microbe at a particular location reaches a predetermined concentration, for example a dangerous level.
  • a predetermined concentration for example a dangerous level.
  • the more infected the treated wound the greater the concentration of enzyme present in the wound, and therefore the shorter the time in which the lysozyme will break down a given chitosan in layer (a), and the higher the degree of deacetylation of a chitosan in layer (a) may be for the lysozyme to degrade it in the same time.
  • the active response device may be for example used to combat a microbe which is associated with pepsin at a particular location and hence to release a treatment material when the concentration of a microbe at the location reaches a predetermined concentration, for example a dangerous level.
  • the thicker layer (a) and/or the lower its molar rate of degradation and/or its transmissibility of the detectable signal is, the longer the release time is.
  • the relevant release time may thus of course be adjusted for a given substance or microbe inter alia by adjusting the nature of the material of the sacrificial layer (a) and/or the thickness of a layer (a) of a given material, to produce an active response device or an assembly of active response devices with a spectrum of release times.
  • Two or more sacrificial layers (a) differing in composition and/or thickness may each may be present in a single active response device in an active response device assembly of two or more active response devices.
  • an active response device assembly comprising two or more active response devices of the first aspect the present invention and which comprises sacrificial layers (a) in each active response device which differ in composition and/or thickness.
  • Each active response device in the assembly will have a discrete signalling layer and a discrete sacrificial layer.
  • the active response devices in the assembly will usually mutually abut in the common planes of their layers.
  • the sacrificial layers (a) differ in thickness, they will usually be made of the same sacrificial material, for example, the same chitosan or derivative thereof, such as an amine salt thereof or alkalised and/or optionally salified organic or inorganic acyloxyalkylchitosans.
  • the sacrificial layers (a) differ in composition, they will usually be made of different modifications of the same sacrificial material, for example, a chitosan or inorganic acyloxyalkylchitosan and derivatives thereof, such as amine salts thereof and alkalised and/or optionally salified organic and inorganic acyloxyalkylchitosans, where the chitosan and hence derivatives thereof, such as amine salts thereof and alkalised and/or optionally salified organic and inorganic acyloxyalkylchitosans, are derived from the deacetylation of chitin to differing levels of deacetylation.
  • a chitosan or inorganic acyloxyalkylchitosan and derivatives thereof such as amine salts thereof and alkalised and/or optionally salified organic and inorganic acyloxyalkylchitosans
  • the sacrificial layers (a) may each be made of essentially different materials.
  • the sacrificial materials comprised in each layer (a) may be specific to different substances and/or microbes, thus providing a single active response device for more than one substance and/or microbe.
  • the active response device according to the invention may be used in a dressing for a wound.
  • a dressing for a wound suitable for detecting and combating a substance or a microbe at the wound, which comprises a dressing layer and an active response device according to the first aspect of the invention, which active response device comprises:
  • the treatment integer (b) is initially shielded from the substance or microbe by the sacrificial layer (a).
  • dressing includes wound coverings, such as adhesive dressings, e.g. plasters, non-adhesive dressings, bandages, and jackets, sleeves and splints for wounded limbs, i.e. where a wound-contacting integer is part of a larger product.
  • an active response device according to the invention in a dressing for a wound is that it may be used to release an appropriate treatment material when treatment needs to be started, intensified or restarted. This is because the active response device will reveal when microbial levels in the wound has reached a predetermined level. Generally this level is chosen such that there is substantially no risk of the patient becoming diseased, failing to recover or relapsing.
  • Suitable examples of a microbial product as a substance include an enzyme, particularly, a lipase, pepsin or dextranase.
  • Examples of a substance associated with the location's response to a microbe where the location is a living human or animal body include an immune cell product, or an enzyme such as lysozyme or a protease.
  • the sacrificial layer preferably comprises a biopolymer such as polytrimethylene succinate, albumin crosslinked polyvinylpyrrolidone, dextran, chitosan and/or derivatives thereof, such as amine salts thereof and alkalised and/or optionally salified organic and inorganic acyloxyalkylchitosans, or polyester amide, more preferably chitosan and/or derivatives thereof, such as amine salts thereof and alkalised and/or optionally salified organic and inorganic acyloxyalkylchitosans.
  • a biopolymer such as polytrimethylene succinate, albumin crosslinked polyvinylpyrrolidone, dextran, chitosan and/or derivatives thereof, such as amine salts thereof and alkalised and/or optionally salified organic and inorganic acyloxyalkylchitosans, or polyester amide, more preferably chitosan and/or derivatives thereof, such as amine salts thereof
  • the active response device is provided with a conventional dressing backing layer which usually covers the active response device on its side away from the wound, and protects it from degradation by an external substance or microbe, and, dependent upon the wound application for which the active response device is to be used, may provide means to secure the dressing to the body, such as an adhesive layer.
  • the backing layer may optionally take any form generally known in the art.
  • the dressing layer could be a non-adhesive gel type dressing such as a hydrogel, an adhesive gel-type dressing, a fluid interactive hydrocolloid dressing capable of adhering to both dry and moist skin surfaces or a hydrocolloid dressing including a polymeric foam layer.
  • the backing layer is preferably a solid, water-insoluble, gas- and water- impervious material which is also impermeable to the treatment material and not degradable by the relevant microbe or a substance associated with the microbe.
  • Suitable in the backing layer include those polymers for any retaining layer, which are described in greater detail hereinbefore.
  • the backing layer is sufficiently stiff to support the active response device and to give it structural rigidity.
  • the backing layer may alternatively not be sufficiently stiff to support the active response device and to give it structural rigidity.
  • Such a backing layer may be provided with an application layer, for example of cardboard that is sufficiently stiff to support the active response device and to give it structural rigidity.
  • the latter layer may be removable after application of the dressing, or if it is not transparent and not removable, it should have a window above the active response device treatment integer.
  • the dressing according to the invention may also be provided with a moisture sensitive active response device adapted to make known to the medical practitioner and/or patient when the dressing is saturated with moisture.
  • a suitable moisture sensitive active response device is, for example, cobalt chloride which changes from blue to pink in the presence of moisture.
  • the dressing according to the invention may optionally include further layers, such as a wound-contacting layer.
  • the treatment integer and/or any part of a permeable retaining layer that lies between the wound and the treatment integer should be at least partially in fluidic communication with the location, and thus any wound- facing layer must be at least partially permeable by the substance or microbe, and wound fluid.
  • this layer may optionally take any form generally known in the art.
  • the layer could be a gauze pad having one or more plies, a non- adhesive gel pad, such as a hydrogel pad, or a fluid interactive hydrocolloid layer.
  • the dressing according to the invention may optionally further comprise, e.g. in any wound-facing layer, a conventional component such as an antiseptic agent, an anti-bacterial agent, and/or an emollient.
  • the active response device is preferably included within the dressing according to the invention by attaching it, for example by moulding, welding or bonding to the backing layer.
  • the active response device layer may be interwoven, interlaced or knitted, or bound, sewn, stitched or tied into or onto the backing layer.
  • a method of treatment or prophylaxis which comprises applying a dressing according to the third aspect of the invention to a wound in a human or animal body.
  • Figure 1 is an exploded schematic perspective view of an active response device according to the invention
  • Figure 2 is a schematic cross-sectional view of an island type dressing incorporating the active response device according to the invention which is shown in Figure 1 or alternative active response devices.
  • Figure 3 is a schematic perspective view of the island type dressing shown in Figure 2.
  • Figure 1 shows one embodiment of an active response device according to the invention.
  • the active response device 6 comprises a treatment integer 7 in the form of a planar disc of absorbent chitosan, here impregnated with polyhexamethylene biguanide (PHMB) hydrochloride antimicrobial, over a coterminous sacrificial layer 8 in the form of a planar biopolymer membrane, here a chitosan layer.
  • PHMB polyhexamethylene biguanide
  • 60% deacetylated chitosan is used as it has been determined experimentally that this level of deacetylation gives a material having the required mechanical and biochemical characteristics, namely a material which is strong enough to handle and which will degrade in the presence of lysozyme.
  • the chitosan sacrificial layer 8 is placed in contact with microbially infected wound fluid containing lysozyme, with the treatment integer 7 distal of the wound.
  • the lysozyme in the wound dissolves the chitosan in the sacrificial layer 8, exposing the treatment integer 7 to the leaching action of wound fluid, thereby releasing the antimicrobial to combat infection in the wound. .
  • Figures 2 and 3 show a dressing 9 comprising an active response device 6 according to the invention, which is to be applied to a wound. It is an island wound dressing 9 which comprises a backing layer top sheet 10 of a water- insoluble, gas- and water-impervious material which is also impermeable to the treatment material, and not degradable by lysozyme, here a thin polyurethane layer overlying the active response device 6 according to the invention.
  • the backing layer 10 is provided with an application layer 16 (not shown) of cardboard, that is sufficiently stiff to support the dressing active response device 6 and to give it structural rigidity during application of the dressing 9, but is removed after application of the dressing 9.
  • the active response device 6 comprises a treatment integer 7, here a disc of planar chitosan, here impregnated with polyhexamethylene biguanide (PHMB) hydrochloride antimicrobial, over a coterminous sacrificial layer 8 in the form of a planar biopolymer membrane, here a 60% deacetylated chitosan layer.
  • a conventional wound-facing layer 1 1 here a gauze pad having one or more plies and which is permeable by the substance or microbe that is to be released to the location encloses the active response device 6 on the underside of the backing layer 10, to which the layer 1 1 is adhered.
  • the treatment integer 7 of the active response device 6 releases the antimicrobial under the leaching action of the wound fluid once the lysozyme therein has degraded and/or eroded enough of the chitosan layer 8 to render it permeable to the wound fluid.
  • the dressing 9 may take other forms.
  • the treatment integer 7 of the active response device 6 may comprise a solid particulate of the antimicrobial treatment material with a chitosan sacrificial layer 8 in the form of a continuous coating encapsulating or enclosing each particle.
  • the gauze pad 1 1 then forms a retaining layer for the treatment integer 7 particulate.
  • the spaces between the fibres of the gauze 1 1 form channels leading from the wound to the sacrificial layer 8 on the treatment integer 7 particles.
  • a high-density polypropylene mesh below the treatment integer 7 particulate may act as a retaining layer.

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Abstract

La présente invention concerne un dispositif de réponse active adapté pour détecter et combattre une substance ou un microbe à un emplacement, ledit dispositif de réponse active comprenant : (a) une couche sacrificielle qui est sensible à la dégradation par la substance ou le microbe ; et (b) un traitement intégré qui est adapté pour libération à l'emplacement d'un matériau de traitement qui lutte contre la substance ou le microbe lors du contact avec l'environnement de l'emplacement ; où, en utilisation, au moins une partie de la couche sacrificielle (a) initialement (i) est située entre le traitement intégré (b) et la substance ou le microbe ; et (ii) est imperméable à la substance ou au microbe ; et le traitement intégré (b) est initialement protégé contre la substance ou le microbe par la couche sacrificielle (a) ; un ensemble comprenant deux dispositifs de réponse active ou plus ; un pansement pour une plaie qui comprend une réponse active ; et un procédé de traitement ou prophylaxie utilisant le pansement.
PCT/EP2012/061122 2011-06-14 2012-06-12 Dispositif de traitement WO2012171920A1 (fr)

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GB201109990A GB201109990D0 (en) 2011-06-14 2011-06-14 Treatment device

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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20230285196A1 (en) * 2022-03-10 2023-09-14 Azadeh Arabshahi Bellows Bandage Drug Delivery System

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2002030478A2 (fr) * 2000-10-13 2002-04-18 Cambridge Meditech Limited Ameliorations en detection

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2002030478A2 (fr) * 2000-10-13 2002-04-18 Cambridge Meditech Limited Ameliorations en detection

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20230285196A1 (en) * 2022-03-10 2023-09-14 Azadeh Arabshahi Bellows Bandage Drug Delivery System

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