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WO1985002190A1 - Materiau polymere bacteriostatique ou fongostatique - Google Patents

Materiau polymere bacteriostatique ou fongostatique Download PDF

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Publication number
WO1985002190A1
WO1985002190A1 PCT/US1984/001825 US8401825W WO8502190A1 WO 1985002190 A1 WO1985002190 A1 WO 1985002190A1 US 8401825 W US8401825 W US 8401825W WO 8502190 A1 WO8502190 A1 WO 8502190A1
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WO
WIPO (PCT)
Prior art keywords
polymer material
active hydrogen
hydrogen atoms
weight
polymer
Prior art date
Application number
PCT/US1984/001825
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English (en)
Inventor
Maurice Hiles
Original Assignee
Maurice Hiles
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 Maurice Hiles filed Critical Maurice Hiles
Publication of WO1985002190A1 publication Critical patent/WO1985002190A1/fr

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    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
    • C08G18/00—Polymeric products of isocyanates or isothiocyanates
    • C08G18/06—Polymeric products of isocyanates or isothiocyanates with compounds having active hydrogen
    • C08G18/28—Polymeric products of isocyanates or isothiocyanates with compounds having active hydrogen characterised by the compounds used containing active hydrogen
    • C08G18/65—Low-molecular-weight compounds having active hydrogen with high-molecular-weight compounds having active hydrogen
    • C08G18/6505—Low-molecular-weight compounds having active hydrogen with high-molecular-weight compounds having active hydrogen the low-molecular compounds being compounds of group C08G18/32 or polyamines of C08G18/38
    • C08G18/6523—Compounds of group C08G18/3225 or C08G18/3271 or polyamines of C08G18/38
    • C08G18/6535—Compounds of group C08G18/3271
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L15/00—Chemical aspects of, or use of materials for, bandages, dressings or absorbent pads
    • A61L15/16—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons
    • A61L15/22—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons containing macromolecular materials
    • A61L15/26—Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds; Derivatives thereof
    • 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
    • A61L26/00—Chemical aspects of, or use of materials for, wound dressings or bandages in liquid, gel or powder form
    • A61L26/0009—Chemical aspects of, or use of materials for, wound dressings or bandages in liquid, gel or powder form containing macromolecular materials
    • A61L26/0019—Chemical aspects of, or use of materials for, wound dressings or bandages in liquid, gel or powder form containing macromolecular materials obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
    • 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
    • A61L26/00—Chemical aspects of, or use of materials for, wound dressings or bandages in liquid, gel or powder form
    • A61L26/0061—Use of materials characterised by their function or physical properties
    • A61L26/0066—Medicaments; Biocides
    • 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
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/14—Macromolecular materials
    • A61L27/18—Macromolecular materials obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
    • 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
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A61L27/54—Biologically active materials, e.g. therapeutic substances
    • 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
    • A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
    • A61L31/04—Macromolecular materials
    • A61L31/06—Macromolecular materials obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
    • 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
    • A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
    • A61L31/14—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A61L31/16—Biologically active materials, e.g. therapeutic substances
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
    • C08G18/00—Polymeric products of isocyanates or isothiocyanates
    • C08G18/06—Polymeric products of isocyanates or isothiocyanates with compounds having active hydrogen
    • C08G18/28—Polymeric products of isocyanates or isothiocyanates with compounds having active hydrogen characterised by the compounds used containing active hydrogen
    • C08G18/30—Low-molecular-weight compounds
    • C08G18/32—Polyhydroxy compounds; Polyamines; Hydroxyamines
    • C08G18/3203—Polyhydroxy compounds
    • C08G18/3218—Polyhydroxy compounds containing cyclic groups having at least one oxygen atom in the ring
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
    • C08G18/00—Polymeric products of isocyanates or isothiocyanates
    • C08G18/06—Polymeric products of isocyanates or isothiocyanates with compounds having active hydrogen
    • C08G18/28—Polymeric products of isocyanates or isothiocyanates with compounds having active hydrogen characterised by the compounds used containing active hydrogen
    • C08G18/30—Low-molecular-weight compounds
    • C08G18/38—Low-molecular-weight compounds having heteroatoms other than oxygen
    • C08G18/3819—Low-molecular-weight compounds having heteroatoms other than oxygen having nitrogen
    • C08G18/3821—Carboxylic acids; Esters thereof with monohydroxyl compounds
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
    • C08G18/00—Polymeric products of isocyanates or isothiocyanates
    • C08G18/06—Polymeric products of isocyanates or isothiocyanates with compounds having active hydrogen
    • C08G18/28—Polymeric products of isocyanates or isothiocyanates with compounds having active hydrogen characterised by the compounds used containing active hydrogen
    • C08G18/65—Low-molecular-weight compounds having active hydrogen with high-molecular-weight compounds having active hydrogen
    • 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
    • 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
    • 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
    • A61L2300/408—Virucides, spermicides

Definitions

  • Th is appl i cation is a continuation- in-part of appl ication Serial No . 550 , 192 fi l ed November 9 , 1983.
  • This invention relates to polymer materials and more particularly, but not exclusively, to preformed polymeric materials which may be used as an interface between damaged outer human or other animal tissue, such as epidermal or epithelial tissue, (herein-after termed "a wound") and its external environment.
  • a wound epidermal or epithelial tissue
  • This invention also relates to controlled microrelease compositions comprising the polymer materials and an active substance, for example a medication system; for bacteristatic and/or fungistatic treatment; to processes for preparing such polymeric materials and such controlled release compositions; and to methods of utilizing them, especially jji vivo.
  • an active substance for example a medication system
  • bacteristatic and/or fungistatic treatment to processes for preparing such polymeric materials and such controlled release compositions; and to methods of utilizing them, especially jji vivo.
  • such an interface should protect the wound from physical trauma; it should prevent agents of infection, such as airborne fungi, bacteria and viruses from gaining access to the wound; it should be transparent to permit visual inspection of the wound; it should prevent maceration of the scab and healing tissue by controlling the moisture of the wound; it should be adequately permeable to gases and vapors; and, as appropriate, it should maintain medication in contact, with the wound.
  • OMPI frequent change to provide observation of healing process and/or to apply medication. This causes patient discomfort, particularly where wound exudate has dried and consolidated the dressing and wound. Moreover, they do not exclude agents of infection.
  • polymer materials have already been suggested for use as a wound dressing, but these have generally been natural and semi -synthetic products such as collagen, gelatin and starch products. These materials are not normally transparent.
  • proteinaceous materials can be allergenic; and furthermore, they do not control agents of infection, indeed, they may provide a nutrient source. Also, since rejection Is often the subject of natural substitutes, it may be that synthetic substition may reduce such rejection tendencies.
  • polyurethane sheet such as for example a B. F. Goodrich polyether polyurethane sold under the Trade Name "Estane,” which
  • -ifiTE OMPI can be up to three thousandths of an inch (75 microns) in thickness, but is commonly less than 45 microns, e.g. about 30 microns.
  • the film is coated on one surface with a continuous or discontinuous layer of suitable adhesive to approximately the same thickness.
  • a continuous or discontinuous layer of suitable adhesive By continuous the patentee means that the adhesive covers the whole surface without any gaps or blank spaces; by discontinuous he means that there is a microporous adhesive, or a pattern of lines or dots of adhesive, the pattern covering the whole surface uniformly, but of course leaving occasional gaps between units of adhesive. Both of these expedients are well known in the coating art, but continuous adhesive is preferred by Seymour to plug any small pinholes in the sheet.
  • the Seymour material consisted of an adhesive-coated sheet material which was liquid-impervious, but had a high moisture-vapour permeability, whereby it was suitable as a wound or burn dressing, or surgical drape or like wound-covering material, wherein the adhesive coating had disseminated throughout its mass an amount of an antibacterial material sufficient to kill bacteria in the wound and surrounding covered skin area.
  • various types of known materials can be used, e.g.:
  • metal salts or like compounds with antibacterial metal ions, e.g. copper, mercury or silver, and optionally with additional nonmetallic ions of antibacterial properties;
  • antibiotics e.g. neomycin, soframycin, bacitracin, polymycin
  • antibacterials such as chlorhexidine and its salts
  • quaternary ammonium compounds e.g. cetrimide, do iphen bromide, polymeric quaternaries
  • the present invention provides polymer materials suitable, inter alia, for use as wound dressings and which are in addition bacteristatic or fungistatic,
  • -W& OMPI preferably bacteriocidal or fungicidal; while still being compatible with healthly tissue.
  • the present invention provides a formed polymer material which is bacteristatic or fungistatic, and which is the reaction product of:
  • a polyisocyanate in amounts less than that stoichiometrically equivalent to the active hydrogen atom content of (a) and (b).
  • the polymer is at least partially chemically cross-linked, preferably through urethane linkages.
  • the precursor may be selected from a wide variety of materials provided only that (i) it has at least two active hydrogen atoms with which to react with the polyisocyanate and thereby become incorporated in the polymeric material of the invention, and that (ii) it imparts elastomeric properties to the formed polymeric material of the invention.
  • suitable precursor polymers include by way of illustration, and not by way of limitation, hydroxy
  • -and/or carboxy- terminated polydiene rubbers such as, for example, SBR and copolymerized interdependent matrix polymers
  • a preferred class of precursor polymers includes diols and triols, with diols being particularly preferred.
  • Diols useful in accordance with the present invention include for example, polyalkylene ether glycols such as polybutylene glycol and/or polypropylene glycol, with the latter being especially preferred.
  • the molecular weight of the precursor polymer is from about 450 to about 3,000 or more, preferably from about 1,500 to 2,500; most commonly about 2,000.
  • the precursor polymer component may be a mixture of suitable polymers.
  • component (b) The essential feature of the chelating agent (component b) is that it can enter into the polymerization reaction conditions while still retaining its ability to act as a chelating agent.
  • component (b) is a chelating agent which has three, and preferably at least four, active hydrogen atoms.
  • Component (b) may also comprise a mixture of suitable chelating agents.
  • one of the active hydrogen atoms of the chelating agent can react with a polyisocyanate, having more than two isocyanate groups, to provide a pendant moiety with two remaining active hydrogen atoms in a configuration such that they can more effectively chelate.
  • two of the active hydrogen atoms may react with a polyisocyanate, having at least two isocyanate groups to provide a backbone moiety with at least two remaining active hydrogen atoms, in a configuration such that they can more effectively chelate.
  • active hydrogen or "active hydrogen atom” shall be understood to mean a pendant hydrogen atom which will react with an isocyanate to produce a urethane moiety
  • suitable active hydrogen atom-containing groups include organic acid groups, typically carboxylic acid groups; primary, secondary and tertiary alcohol groups; and primary and secondary amine and amide groups. At least one such group will desirably be present.
  • Other suitable chelating groups include carboxyl groups, carboxylic acid ester groups, and tertiary amine and amide groups. At least one such group may also be present.
  • chelating agents containing only active hydrogen atom-containing chelating groups mention may be made of sugars and sugar alcohols such as sorbitol and mannitol, iminodiacetic acid (HOOC CH.,) £ NH (“IDAA”) and its corresponding alcohol. It is particularly preferred, however, that the chelating agent comprises both (i) one or more active hydrogen atom-containing chelating groups, especially carboxylic acid and alcohol groups, and (ii) also one or more chelating groups which do not contain active hydrogen atoms, especially tertiary amine and amide groups.
  • a preferred class of chelating agents includes, those having at least four active hydrogen atom-containing groups and at least two chelating groups which do not contain active hydrogen atoms; for example, tetraethylene pentamine heptacetic acid (TPHA).
  • TPHA tetraethylene pentamine heptacetic acid
  • a particularly preferred subclass comprises compounds of the formula: X 1 R 1 R 2 X 2
  • X,, X ⁇ , X, and X. may be the same or different, each represents a substituted or unsubstituted active hydrogen atom-containing group, preferably a primary, secondary or tertiary alcohol or carboxylic acid group;
  • R,, R 2 , R, amd R. may be the same or different and each represents a substituted or unsubstituted C, to C. alkylene or alkylidene group, preferably a methylene, ethyl ene, or isopropylene group, with the proviso that R, amd R. and/or R_ and R-, may, together with the nitrogen atom to which they are bonded, form a 5 to 8 membered heterocyclic ring;
  • n is an integer from 1 to 5 , preferably 2 or 3; and
  • R ⁇ and R 6 may be the same or different, and each represents a hydrogen atom or a substituted or unsubtituted C, to C.. alkyl group, preferably a hydrogen atom, with the proviso that R-. and R, may, together with the carbon atoms to which they are bonded, form a 5 to 8 membered carboxylic ring.
  • n is greater than 1
  • the several R ⁇ may be the same or different and/or the several R 6 may be the same or different; and/ or (ii) two R 5 and/ or two R, may, together with the carbon atoms to which they are bonded, form a 5 - 8 membered carboxylic system.
  • Ethylene diamine derivatives are especially preferred. Specific examples include ethylenediamine tetracetic acid (EDTA) and its corresponding alcohols, bis-B- hydroxyethylene ethylenediamine diacetic acid and tetrakis-B- hydroxyethylene ethylenediamine;
  • CDTA 2-diaminocyclohexane-N,N,NJ"N -tetracetic acid
  • CDTA 2-diaminocyclohexane-N,N,NJ"N -tetracetic acid
  • Tetrakis-B-hydroxyethylene ethylenediamine and tetrakis-hydroxym thyl ne ethylene diamine are particularly preferred.
  • Component (c), where present, may be one or more members selected from the variety of metal-containing compounds known to catalyze urethane formations by the reaction between isocyanate group-containing compounds and active hydrogen atom-containing compounds, Suitable metals include cadmium, calcium, cobalt, copper, gold, lead, magnesium, manganese, mercury, nickel, silver, tin, titanium, zinc, and zirconium with calcium and mercury, especially mercury, being preferred.
  • the metal may be present as a simple salt (eg.
  • the amount of component (c), where present, is small; typically from about 0.001 to about 0.2% or less preferably from 0.0025 to 0.1%, especially from 0.005 to 0.05%, by weight based on the weight of the reaction mixture.
  • component (c) need not be present.
  • certain bases especially tertiary amine-containing compounds, can catalyze the urethane formation reaction; and may be used instead.
  • catalysts include ethylene diamine, triethylenediamine (sold under the trade name "DABCO") and triethanoldiamine.
  • a particularly preferred class of such catalysts are those chelating agents which have at least one tertiary amine group ; these compounds are autocatalytic in the presence of an isocyanate.
  • One or more other metals may be introduced into the polymer material to provide bacteristatic and/or fungistatic efficiency. These may be added to the reaction mixture, and may also function as a catalyst to the urethane reaction, or may be subsequently added to the formed polymer material.
  • the polyisocyanate is preferably a diisocyanate.
  • Aromatic diisocyanates are preferred with bis-( -isocyanatophenyl) methane being particularly preferred.
  • the polyisocyanate should preferably be present in amounts less than that stoichiometrically equivalent to the active hydrogen atom content of components (a) and (b). This will ensure that the active hydrogen atom-containing groups required for chelation are preserved.
  • Fillers such as chalk or talc
  • plasticizers such as adipate, phosphate and phthalate esters, for example dioctyl phthalate
  • filler may be omitted so that the resulting dressing may be transparent to enable medical inspection without removal.
  • the present invention also provides a process for the preparation of a polymer material as aforesaid, which process comprises:
  • the weight ratio of precursor polymer to chelating agent is preferably from about 1:1 to about 4:1.
  • the weight ratio of active hydrogen atom-containing components, and plasticizer to polyisocyanate is preferably from about 5:1 to about 11:1.
  • a wound dressing for application to post-operative, accidental (such as burns) or pathological (such as diabetes or hemorrhoids) tissue damage, which comprises a polymer material as aforesaid.
  • the polymer material is preferably formed, in any conventional manner, such as, for example, a sheet, typically less than 1/8", for example from .01 to .1" in thickness.
  • a gauze for example, a nylon gauze onto which the reaction mixture is cast, moulded or calendered.
  • the metal is generally added to the polyol mixture at a relatively low level, often as low as about 0.001%, in the form of a soluble salt, and more preferably, in the form of a soluble organo salt.
  • a soluble salt for example, phenyl mercuric acetate.
  • the metal can also function as a urethane catalyst, its form remaining unchanged throughout the reaction.
  • This invention further provides a method of treating human or other living tissue with a polymer material as aforesaid, which method comprises applying to a locus in the human or other living tissue a therapeutically effective amount of the polymer material.
  • the locus may comprise a wound as aforesaid or a tumor. In the latter case the application may even involve implantation of the therapeutically effective amount of the polymer material.
  • This invention still further provides an endoprosthesis, for example an osseous or cartiligenous material substitute or a vascular graft which may readily be treated to impart anticoagulant activity, comprising a polymer material as aforesaid.
  • an endoprosthesis for example an osseous or cartiligenous material substitute or a vascular graft which may readily be treated to impart anticoagulant activity, comprising a polymer material as aforesaid.
  • This invention provides surgical instrumentation comprising a polymer material as aforesaid.
  • the surgical instrument may be completely or in part cast from the polymer or coated therewith.
  • the polymer material of the invention is also very suitable for plasmaferesis or asphaferesis.
  • EXAMPLE 1 1 part of tetrahydroxym thyl ethylene diamine, 2 parts of a polypropylene glycol of number average molecular weight 2,000 and 0.005 parts of phenyl mercury acetate (as a catalyst) were thoroughly mixed in a reactor for 3 hours at 160°F at a pressure of 20 inches Hg. The water content was maintained at less than 0.05%. The mixture was then cooled to room temperature while maintaining the partial vacuum. 0.6 part of bis-(4-isocyanato henyl) methane
  • Example 1 was repeated with inclusion of 0.6 parts of dioctyl phthatlate as plasticizer, in the mixture.
  • EXAMPLE 3 S_. aureus bacteria were streaked onto bovine blood agar in a Petri dish. This culture was then incubated at 37°C at atmospheric pressure for 24 hours. Then a 1 mm cube of the polymer material of Example 1 was placed in the center of the dish and the incubation was continued. The area of inhibition was observed after 24 hours (day 1) whereupon the cube was removed, washed with phosphate buffer and placed onto a freshly incubated Petri dish culture; and the process was repeated to give the following results:
  • EXAMPLE 4 100 macrophage cells taken from the peritoneum of an anaesthetized Bab C mouse were counted onto, as control, a clean glass plate. A like number were counted onto a 500 film of the polymer material of Example 1. Both samples were then incubated at 37°C at atmospheric pressure. A further count was made after 4 hours. The average spread, a measure of macrophage activation, on the control was 2% while that on the film was 36%. Incubation was continued and a further count was made 4 hours later. No further spread was observed, indicating that macrophage activation was essentially complete within 4 hours.
  • the activated macrophages were returned to the periotoneum of a Bab C mouse in which tumor growth had been induced by earlier introduction of tumor culture.
  • the macrophages became phagocysistic and all tumors were apparently terminated.
  • the present invention is particularly useful in taking advantage of calcium.
  • calcium Apart from being by far the major component of bone structure, calcium also contributes to many other important physiological functions. There are two which are particularly pertinent in this instance.
  • calcium is a stabilizing component in the nucleus of a macrophage such that, if the level is increased or decreased, the micro-organism becomes phagocystically activated.
  • coagulation is generally regarded as essentially beneficial and, in the case of hemophillia, critical, there are circumstances where retardation, but not elimination, of the process could be advantageous. For instance, additional supplies of blood transporting immune response organisms could be helpful in dealing with excessive infection at a wound site.
  • the present invention provides a means to take advantage of all of these.
  • Calcium as a soluble salt, such as gluconate or levulinate, is readily accepted by the polymer and a very loose bonded chelation occurs.
  • a soluble salt such as gluconate or levulinate
  • mice were injected with 1.5ral of a 10% proteose peptone solution 4 days prior to harvest and sacrificed by CO asphyxiation. Then 4.0ml of Alsever's solution was injected and the abdomen massaged. The peritoneum was then incised, the exudate drained, and the supernatant was separated by centrifuge. Macrophages were counted and divided equally into three identical nutrient solutions:
  • HDPE high density polyethylene
  • ameboid macrophages secrete enzymes one of which is Interleuken 1. This enzyme is a trigger for fibroblast activation and therefore, and deposition of collagen and interferon protein..
  • the normal response time for what may be the vital micro-organisms, is dramatically decreased in the presence of the polymer of Example 1. For example:
  • endothelial cells When endothelial cells are introduced to the polymer of Example 1, they adhere and they survive. It is not yet clear under what conditions they divide without additional encouragement. However, if the polymer of Example 1 is micro-coated with fiber-nectin, the cells not only proliferate, but apparently encourage the activity of fibroblasts.
  • OMPI A practical example is illustrated by the treatment of a juvenile-onset diabetic, who was sufffering from chronic mellitus ulceration of the tissue adjacent to the lateral malleolus. The lesion had been treated for five yeas without improvement and below the knee ("BK") amputation was imminent. The ulcer site was covered with dressing 2.5" x 2.5" x 0.05", formed from the polymer of Example 1.
  • the present invention is thus specifically of particular advantage for use in wound dressing; burn management; control of bacterial, fungal, viral, spiroteche and parasitic infections; as an anti-coagulant (Ca-) in vascular grafts; as a coagulant (Ca+) in hemophillia; as a filter component for aspheresis; as a local immuno stimulant; and for anti-tumor activity.
  • control of calcium at the wound site is particularly advantageous and was not heretofore possible.

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Epidemiology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Medicinal Chemistry (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Engineering & Computer Science (AREA)
  • Materials Engineering (AREA)
  • Organic Chemistry (AREA)
  • Polymers & Plastics (AREA)
  • Molecular Biology (AREA)
  • Transplantation (AREA)
  • Biomedical Technology (AREA)
  • Dermatology (AREA)
  • Oral & Maxillofacial Surgery (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Surgery (AREA)
  • Vascular Medicine (AREA)
  • Hematology (AREA)
  • Materials For Medical Uses (AREA)
  • Addition Polymer Or Copolymer, Post-Treatments, Or Chemical Modifications (AREA)
  • Polymers With Sulfur, Phosphorus Or Metals In The Main Chain (AREA)

Abstract

Matériau polymère formé possédant des propriétés bactériostatiques ou fongostatiques, qui est le produit de réaction de: (a) un polymère précurseur possédant au moins deux atomes d'hydrogène actifs capables de conférer au matériau polymère des propriétés élastomères; (b) un agent de chélation possédant au moins un atome d'hydrogène actif; (c) de 0 à environ 0,2% en poids, basé sur le poids du mélange de réaction, d'un catalyseur de formation d'uréthane contenant du métal; et (d) un polyisocyanate en quantités inférieures à la quantité stoechiométriquement équivalente à la teneur en atomes d'hydrogène actifs de (a) et (b).
PCT/US1984/001825 1983-11-09 1984-11-09 Materiau polymere bacteriostatique ou fongostatique WO1985002190A1 (fr)

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
US55019283A 1983-11-09 1983-11-09
US550,192 1983-11-09
US66828784A 1984-11-05 1984-11-05
US668,287 1984-11-05

Publications (1)

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EP (1) EP0160700A1 (fr)
AU (1) AU3674084A (fr)
WO (1) WO1985002190A1 (fr)

Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE3826962A1 (de) * 1988-08-09 1990-02-15 Harry Prof Dr Rosin Arzneimittel zur oralen verabreichung mit einem gehalt an nichtresorbierbaren metallkomplexbildnern
EP0482467A2 (fr) * 1990-10-15 1992-04-29 Nisshinbo Industries, Inc. Adhésif chirurgical
DE19704158A1 (de) * 1997-02-04 1998-08-06 Fischer Artur Werke Gmbh Polyurethanzusammensetzung mit verbesserter langzeitresistenz gegen Mikroorganismenbefall
US6716895B1 (en) 1999-12-15 2004-04-06 C.R. Bard, Inc. Polymer compositions containing colloids of silver salts
US8034454B2 (en) * 1999-12-15 2011-10-11 C.R. Bard, Inc. Antimicrobial compositions containing colloids of oligodynamic metals

Citations (11)

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Publication number Priority date Publication date Assignee Title
US2953533A (en) * 1958-04-04 1960-09-20 Allied Chem Highly cross-linked non flammable polyurethane foams and preparation of same
US3112281A (en) * 1957-09-17 1963-11-26 Wyandotte Chemicals Corp Polyurethane foams and process for preparing same
US3136731A (en) * 1961-03-09 1964-06-09 Bayer Ag Method of preparing polyurethane with a delayed action catalyst
US3255253A (en) * 1962-07-30 1966-06-07 Union Carbide Corp Amine-containing polyols
US3799898A (en) * 1970-01-05 1974-03-26 Scott Paper Co Stable hydrophilic polyurethane foams prepared by using a surfactant soluble in the hydrophilic polyol reactant
US3822238A (en) * 1972-08-02 1974-07-02 Princeton Polymer Lab Hydrophilic polyurethane polymers
US3975350A (en) * 1972-08-02 1976-08-17 Princeton Polymer Laboratories, Incorporated Hydrophilic or hydrogel carrier systems such as coatings, body implants and other articles
US4173689A (en) * 1976-02-03 1979-11-06 University Of Utah Synthetic polymer prosthesis material
USRE31389E (en) * 1976-11-12 1983-09-20 Caschem, Inc. Non-wicking polyurethane casting systems
US4424305A (en) * 1980-11-12 1984-01-03 Tyndale Plains-Hunter, Ltd. Surgical implants formed of polyurethane diacrylate compositions
US4433128A (en) * 1981-11-27 1984-02-21 Akzo Nv Embedding mass based upon fast-reacting polyurethane casting resin

Patent Citations (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3112281A (en) * 1957-09-17 1963-11-26 Wyandotte Chemicals Corp Polyurethane foams and process for preparing same
US2953533A (en) * 1958-04-04 1960-09-20 Allied Chem Highly cross-linked non flammable polyurethane foams and preparation of same
US3136731A (en) * 1961-03-09 1964-06-09 Bayer Ag Method of preparing polyurethane with a delayed action catalyst
US3255253A (en) * 1962-07-30 1966-06-07 Union Carbide Corp Amine-containing polyols
US3799898A (en) * 1970-01-05 1974-03-26 Scott Paper Co Stable hydrophilic polyurethane foams prepared by using a surfactant soluble in the hydrophilic polyol reactant
US3822238A (en) * 1972-08-02 1974-07-02 Princeton Polymer Lab Hydrophilic polyurethane polymers
US3975350A (en) * 1972-08-02 1976-08-17 Princeton Polymer Laboratories, Incorporated Hydrophilic or hydrogel carrier systems such as coatings, body implants and other articles
US4173689A (en) * 1976-02-03 1979-11-06 University Of Utah Synthetic polymer prosthesis material
USRE31389E (en) * 1976-11-12 1983-09-20 Caschem, Inc. Non-wicking polyurethane casting systems
US4424305A (en) * 1980-11-12 1984-01-03 Tyndale Plains-Hunter, Ltd. Surgical implants formed of polyurethane diacrylate compositions
US4433128A (en) * 1981-11-27 1984-02-21 Akzo Nv Embedding mass based upon fast-reacting polyurethane casting resin

Cited By (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE3826962A1 (de) * 1988-08-09 1990-02-15 Harry Prof Dr Rosin Arzneimittel zur oralen verabreichung mit einem gehalt an nichtresorbierbaren metallkomplexbildnern
EP0482467A2 (fr) * 1990-10-15 1992-04-29 Nisshinbo Industries, Inc. Adhésif chirurgical
EP0482467A3 (en) * 1990-10-15 1993-03-03 Nisshinbo Industries, Inc. Surgical adhesive
DE19704158A1 (de) * 1997-02-04 1998-08-06 Fischer Artur Werke Gmbh Polyurethanzusammensetzung mit verbesserter langzeitresistenz gegen Mikroorganismenbefall
US6716895B1 (en) 1999-12-15 2004-04-06 C.R. Bard, Inc. Polymer compositions containing colloids of silver salts
US8034454B2 (en) * 1999-12-15 2011-10-11 C.R. Bard, Inc. Antimicrobial compositions containing colloids of oligodynamic metals

Also Published As

Publication number Publication date
AU3674084A (en) 1985-06-03
EP0160700A1 (fr) 1985-11-13

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