EP3745998A1 - Polymère antimicrobien destiné à être utilisé dans des implants ophtalmiques - Google Patents

Polymère antimicrobien destiné à être utilisé dans des implants ophtalmiques

Info

Publication number
EP3745998A1
EP3745998A1 EP18903224.6A EP18903224A EP3745998A1 EP 3745998 A1 EP3745998 A1 EP 3745998A1 EP 18903224 A EP18903224 A EP 18903224A EP 3745998 A1 EP3745998 A1 EP 3745998A1
Authority
EP
European Patent Office
Prior art keywords
methacrylate
monomer
antimicrobial
monomers
copolymer
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Pending
Application number
EP18903224.6A
Other languages
German (de)
English (en)
Other versions
EP3745998A4 (fr
Inventor
Yichieh Shiuey
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Keramed Inc
Original Assignee
Keramed Inc
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 Keramed Inc filed Critical Keramed Inc
Publication of EP3745998A1 publication Critical patent/EP3745998A1/fr
Publication of EP3745998A4 publication Critical patent/EP3745998A4/fr
Pending legal-status Critical Current

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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
    • 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
    • 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
    • A61F2/00—Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
    • A61F2/02—Prostheses implantable into the body
    • A61F2/14—Eye parts, e.g. lenses or corneal implants; Artificial eyes
    • A61F2/142—Cornea, e.g. artificial corneae, keratoprostheses or corneal implants for repair of defective corneal tissue
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/74—Synthetic polymeric materials
    • A61K31/785—Polymers containing nitrogen
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
    • A61K9/0024—Solid, semi-solid or solidifying implants, which are implanted or injected in body tissue
    • 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
    • A61L27/16—Macromolecular materials obtained 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
    • A61L27/14—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
    • A61L27/14—Macromolecular materials
    • A61L27/26—Mixtures of macromolecular compounds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • 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
    • A61L27/52—Hydrogels or hydrocolloids
    • 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
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08F—MACROMOLECULAR COMPOUNDS OBTAINED BY REACTIONS ONLY INVOLVING CARBON-TO-CARBON UNSATURATED BONDS
    • C08F20/00—Homopolymers and copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and only one being terminated by only one carboxyl radical or a salt, anhydride, ester, amide, imide or nitrile thereof
    • C08F20/02—Monocarboxylic acids having less than ten carbon atoms, Derivatives thereof
    • C08F20/10—Esters
    • C08F20/34—Esters containing nitrogen, e.g. N,N-dimethylaminoethyl (meth)acrylate
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08F—MACROMOLECULAR COMPOUNDS OBTAINED BY REACTIONS ONLY INVOLVING CARBON-TO-CARBON UNSATURATED BONDS
    • C08F220/00—Copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and only one being terminated by only one carboxyl radical or a salt, anhydride ester, amide, imide or nitrile thereof
    • C08F220/02—Monocarboxylic acids having less than ten carbon atoms; Derivatives thereof
    • C08F220/10—Esters
    • G—PHYSICS
    • G02—OPTICS
    • G02B—OPTICAL ELEMENTS, SYSTEMS OR APPARATUS
    • G02B1/00—Optical elements characterised by the material of which they are made; Optical coatings for optical elements
    • G02B1/04—Optical elements characterised by the material of which they are made; Optical coatings for optical elements made of organic materials, e.g. plastics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/20—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing organic materials
    • A61L2300/204—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing organic materials with nitrogen-containing functional groups, e.g. aminoxides, nitriles, guanidines
    • A61L2300/208—Quaternary ammonium compounds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/40—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
    • A61L2300/404—Biocides, antimicrobial agents, antiseptic agents
    • 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
    • A61L2430/00—Materials or treatment for tissue regeneration
    • A61L2430/16—Materials or treatment for tissue regeneration for reconstruction of eye parts, e.g. intraocular lens, cornea

Definitions

  • the present invention relates generally to ophthalmic implant devices and methods for their preparation and use, and more particularly, to antimicrobial polymers, obtained by copolymerizing at least one antimicrobial monomer with at least one other monomer for use in an ophthalmic implant device.
  • Infections are serious complications of ophthalmic implant surgery.
  • ocular implants include intraocular lenses, glaucoma valves, and artificial corneas, which are also known as keratoprostheses.
  • An uncontrolled infection after ophthalmic implant surgery of any of these devices can result in loss of vision or even loss of the eye.
  • Contact lenses are clear lenses that float on the human tear film. They are not physically attached to the eye in any way and direct contact between the contact lens and tissue is known to cause complications including comeal abrasions, infections and comeal scarring.
  • a contact lens’ purpose is to refract light to allow proper focus of light rays onto the retina.
  • an ophthalmic implant is any device; clear, translucent or opaque, that can be embedded inside ocular tissue.
  • An ophthalmic implant must be biocompatible with the ocular tissues in order to function.
  • Another strategy which has been proposed in the past, is to infuse the polymer of the ophthalmic implant with an antibacterial metal ion.
  • silver and copper metal have been proposed as agents to be infused into polymers for use in an ophthalmic implant.
  • free metal ions as an antibacterial agent within polymers has been used widely in commercial plastic goods and in some short-term disposable medical devices such as catheters, metal ions are known to be dangerous in the eye.
  • Argyrosis is the medical term for silver toxicity of the eye. Argyrosis has been reported to result in a slate gray discoloration of the conjunctiva and iris. Argyrosis has also been found to result in cataracts and retinal maculopathy, both of which are vision threatening conditions.
  • Copper toxicity in the eye results in a characteristic green ring around the cornea, which is termed a Kayser-Fleischer ring. Moreover, studies have demonstrated that copper toxicity can induce ocular complications such as intraocular inflammation (uveitis), hemorrhage, vitreous liquefaction, hypotony, iris ischemia and retinal damage. [0011] In addition, free metal ions may also leach out of the polymer over time and therefore, the polymer may lose its antimicrobial properties over time.
  • the invention provides antimicrobial polymers for use in an ophthalmic implant obtained by copolymerizing at least one antimicrobial monomer and at least one monomer selected from an acrylic, silicone, vinyl or collagen monomer.
  • the invention also provides methods for preparing an antimicrobial polymer for use in an ophthalmic implant, by reacting at least one antimicrobial monomer with at least one other monomer selected from an acrylic, silicone, vinyl and collagen monomer to provide the antimicrobial polymer; and using the antimicrobial polymer in the ophthalmic implant.
  • the copolymers of the present invention are antimicrobial, biocompatible, and reversibly deformable and are also clear, translucent or opaque. These characteristics are desirable for the optimal function of ophthalmic implants that are designed for implantation inside ocular tissue through small incisions. Moreover, because the entire co-polymer, not just the surface of the co-polymer, has antimicrobial properties, ophthalmic implants made from these types of co-polymers will not lose their antimicrobial properties even if the surface of the implant becomes eroded over time. This is particularly important for ophthalmic implants that are exposed to the surface of the eye, where blinking will cause erosion of the polymeric material. When the surface of the polymer of the present invention is eroded, the antimicrobial polymer beneath the surface will still kill microbes and thereby decrease the infection risk for the patient.
  • FIG. 1 illustrates an embodiment of the polymerization of an antimicrobial, clear, biocompatible, reversibly deformable polymer.
  • the present disclosure provides antimicrobial polymers for use in ophthalmic implants, which are obtained by copolymerizing at least one antimicrobial monomer with at least one other monomer selected from an acrylic, silicone, vinyl or collagen monomer.
  • the resulting antimicrobial polymer provides an antimicrobial, biocompatible, and reversibly deformable implant, which are also clear, translucent or opaque. These characteristics are desirable for the optimal function of ophthalmic implants that are designed for implantation inside ocular tissues through small incisions.
  • the entire copolymer, not just the surface of the copolymer has antimicrobial properties, ophthalmic implants made from this type of copolymer will not lose their antimicrobial properties even if the surface of the implant becomes eroded over time. This is particularly important for ophthalmic implants which are exposed to the surface of the eye, where blinking will cause erosion of the polymeric material.
  • ophthalmic implants there are many types of ophthalmic implants.
  • One type of such implant is an artificial cornea.
  • the copolymer is contemplated to be antimicrobial, clear, biocompatible and reversibly deformable.
  • ophthalmic implants do not need to be clear to perform their intended function.
  • glaucoma valves, retinal prostheses and intracorneal implants outside of the visual axis do not need to refract light as part of their function and therefore, they may be translucent or opaque.
  • the polymer of the present invention may be translucent or opaque.
  • Various ophthalmic implants and methods thereof, have been fully described in U.S. Patent Nos.
  • Antimicrobial polymers are a class of polymers having antimicrobial activity, or the ability to inhibit the growth of microorganisms such as bacteria, fungi and/or protozoans. These polymers mimic antimicrobial peptides, which are used by the immune systems of living animals to kill various microbes. Antimicrobial polymers are generally nonvolatile and chemically stable, and are used in the areas of medicine as a means to fight infection, in the food industry to prevent bacterial contamination, and in water sanitation to inhibit the growth of microorganisms in drinking water.
  • Antimicrobial polymers kill microorganisms on contact by causing their cells to burst.
  • antimicrobial polymers generally possess a positive charge, and can be readily adsorbed onto the negative surface of the cell wall of a bacteria. Once adsorbed, the antimicrobial polymer then diffuses through the cell wall where it binds to and disrupts the cell membrane. While adsorption is best achieved by cationic antimicrobial polymers, small molecule antimicrobial agents excel at diffusion due to their low molecular weight. The disruption of the cell membrane and subsequent leakage of cytoplasmic constituents leads to the death of the bacteria.
  • FIG. 1 illustrates an embodiment of the polymerization of an antimicrobial, clear, biocompatible, reversibly deformable polymer.
  • the antimicrobial polymers are obtained by copolymerizing at least one antimicrobial monomer with at least one monomer selected from an acrylic, silicone, vinyl or collagen monomer. After polymerization, the resulting polymeric network includes the immobilized antimicrobial polymer spaced throughout the network.
  • the antibacterial monomer is selected from quaternary ammonium salt based monomers.
  • a non-limiting example of a quaternary ammonium salt based monomer is l-[l2-(methacryloyloxy)dodecyl]pyridinium bromide (MDPB):
  • MDPB has been used as an antimicrobial monomer to reduce the risk of dental caries when copolymerized with dental adhesives and dental resins.
  • the least one antimicrobial monomer is a quaternary ammonium salt based monomer such as methacryloxylethyl cetyl dimethyl ammonium chloride (DMAE-CB).
  • DMAE-CB methacryloxylethyl cetyl dimethyl ammonium chloride
  • the least one antimicrobial monomer is a quaternary ammonium salt based monomer such as 2-methacryloxyethyl dodecyl methyl ammonium bromide (MAE-DB):
  • the least one antimicrobial monomer is a quaternary ammonium salt based monomer such as 2-methacryloxyethyl hexadecyl methyl ammonium bromide (MAE-HB):
  • the least one antimicrobial monomer is a quaternary ammonium salt based monomer such as bis(2-methacryloxyethyl) dimethyl ammonium bromide (IDMA-l):
  • the at least one antimicrobial monomer may differ based on the alkyl chain length.
  • these include but are not limited to dimethylamino propyl methacrylate (DMAPM), dimethylamino hexyl methacrylate (DMAHM), dimethylamino heptyl methacrylate (DMAHPM), dimethylamino octyl methacrylate (DMAOM), dimethylamino nonyl methacrylate (DMANM), dimethylamino decyl methacrylate (DMADM), dimethylamino undecyl methacrylate (DMAIIDM), dimethylamino dodeeyl methacrylate (DMADDM), dimethylamino tridecyl methacrylate (DMATDM), dimethylamino tetradecyl methacrylate (DMATTDM), dimethylamino pentadecyl methacrylate (DMAPDM), dimethylamino hexyl methacrylate (
  • the antimicrobial monomer may have a primary, secondary or tertiary amino group.
  • antibacterial monomers include but are not limited to ortho-, meta-, and/or para-dimethylaminomethyl styrene, N[2- dimethylamino)ethyl] acrylamide, N-(2-aminoethyl)acrylamide, n-butylacrylamide, and diallyl-dimethyl ammonium salts.
  • the antimicrobial monomer may be covalently linked to an antimicrobial peptide.
  • antimicrobial peptides include but are not limited to: b- sheet peptides stabilized by two to four disulfide bridges (e.g., human a- and defensins, plectasin or protegrins); a-helical peptides (e.g., LL-37, cecropins or magainins); extended structures rich in glycine, proline, tryptophan, arginine or histidine (e.g., indolicidin); and loop peptides with one or disulfide bridge (e.g., bacteriocins).
  • disulfide bridges e.g., human a- and defensins, plectasin or protegrins
  • a-helical peptides e.g., LL-37, cecropins or magainins
  • the at least one other monomer is selected from an acrylic, silicone, vinyl, or collagen monomer. These monomers can undergo polymerization with the at least one antimicrobial monomer described above to provide the antimicrobial polymers for use in ophthalmic implants.
  • the ophthalmic implant may be formed from a single blank or block of material typically a polymeric hydrogel of a type commonly employed in forming intraocular lenses (IOL'S), such as a copolymer of hydroxyethyl methacrylate and methylmethacraylate, or a hydrophobic acrylic material.
  • IOL'S intraocular lenses
  • the polymeric hydrogel material could also have both hydrophobic and hydrophilic properties, such as a copolymer of hydroxyethyl methacrylate and methylmethacraylate that has undergone plasma surface treatment.
  • the ophthalmic implant could be molded, machined, or laser cut from a collagen-based hydrogel.
  • the at least one other monomer is selected a hydrophobic acrylic monomer.
  • hydrophobic acrylic monomers include but are not limited to: [0034] monomers of phenylethyl acrylate, phenylethyl methacrylate and butanediol diacrylate, which form a copolymer of phenylethyl acrylate and phenylethyl methacrylate, cross linked with butanediol diacrylate ( AcrySof ' IOL) available from Alcon, A Novartis Division, 6201 South Freeway, Fort Worth, TX 76134-2001;
  • the at least one other monomer is selected a hydrophilic acrylic monomer.
  • hydrophilic acrylic monomers include but are not limited to:
  • the at least one other monomer is biocompatible with the cornea, the eye and the body. Suitable monomers include but are not limited to one or more monomers selected from collagen, urethanes, (2-hydroxyethylmethacrylate), vinylpyrolidone, glycerolmethacrylate, vinyl alcohol, ethylene glycol, methacrylic acid, silicones, acrylics, fluorocarbons, and monomers with phosphocholine.
  • the at least one other monomer comprises a hydrogel.
  • the material comprises methacrylic acid and hydroxyethyl methacrylate (PHBMA/MAA).
  • the at least one other monomer is a material comprising a reversibly deformable acrylic monomer, such as those used for intraocular lenses.
  • suitable monomers include but are not limited to hydroxyethyl methacrylate and methyl methacrylate.
  • the monomers provide a deformable polymer that is hydrophilic in nature in order to allow smooth wetting of the optical surface of the implant. Wetability is an important characteristic of an ophthalmic implant to allow the tear film to act as a good optical interface.
  • the ophthalmic implant may be manufactured from monomers that promote epithelialization on the surface of the implant.
  • monomers include collagen and N— isopropylacrylamide, collagen and l-ethyl3.3'(dimethyl- aminopropyll-carbodiimide as well as collagen and N-hydroxysuccinimide (EDC/NHS).
  • the polymer may additionally contain extracellular matrix proteins such as fibronectin, laminin, substance P, insulin-like growth factor- 1, or peptide sequences such as fibronectin adhesion-- promoting or peptide (FAP).
  • the at least one other monomer is an acrylic monomer.
  • an acrylic monomer include but are not limited to methyl acrylate (MA) and methyl methacrylate (MMA).
  • PMA poly(methacrylate)
  • PMMA poly(methyl methacrylate)
  • MA and MMA are irritants
  • polymers of MA and MMA are biocompatible, resistant to long exposure to temperatures, and the chemistry and cell action of human tissues.
  • Acrylic monomers can undergo polymerization with the at least one antimicrobial monomer described above to provide the antimicrobial polymers for use in ophthalmic implants.
  • the at least one other monomer is a silicone.
  • Silicones have formula: R2S1O, where R is an organic group such as methyl, ethyl, or phenyl. Silicones can undergo polymerization to form polysiloxanes, which include a repeating inorganic silicon- oxygen backbone chain (— Si-O-Si-O-Si-O— ) with the organic side group R attached to the tetravalent silicon atom.
  • polysiloxanes can be synthesized with a wide variety of properties and compositions. They can vary in consistency from liquid to gel to rubber to hard plastic.
  • siloxane is the linear polydimethylsiloxane (PDMS), a silicone oil.
  • PDMS linear polydimethylsiloxane
  • Silicone monomers can also undergo polymerization with the at least one antimicrobial monomer described above to provide the antimicrobial polymers for use in ophthalmic implants.
  • the at least one other monomer is a vinyl monomer.
  • the at least one other monomer is a collagen monomer.
  • a single collagen molecule, tropocollagen, is used to make up larger collagen aggregates, such as fibrils. Fibrils are made up of three polypeptide strands, each of which has the confirmation of a left- handed helix.
  • collagen monomers may be linked to one or more acrylate or vinyl monomers using various linkers.
  • Collagen monomers can also undergo polymerization with the at least one antimicrobial monomer described above to provide the antimicrobial polymers for use in ophthalmic implants.
  • the ophthalmic implant may include collagen and N- isopropylacrylamide, collagen and l-ethyl-3,3'(dimethylaminopropyl)-carbodiimide as well as collagen and N-hydroxysuccimmide (EDC/NHS).

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Transplantation (AREA)
  • Epidemiology (AREA)
  • Oral & Maxillofacial Surgery (AREA)
  • Dermatology (AREA)
  • Engineering & Computer Science (AREA)
  • Biomedical Technology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Molecular Biology (AREA)
  • Polymers & Plastics (AREA)
  • Organic Chemistry (AREA)
  • Physics & Mathematics (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Ophthalmology & Optometry (AREA)
  • Cardiology (AREA)
  • Vascular Medicine (AREA)
  • Neurosurgery (AREA)
  • Dispersion Chemistry (AREA)
  • Optics & Photonics (AREA)
  • General Physics & Mathematics (AREA)
  • Materials For Medical Uses (AREA)
  • Addition Polymer Or Copolymer, Post-Treatments, Or Chemical Modifications (AREA)
  • Prostheses (AREA)
  • Eyeglasses (AREA)

Abstract

La présente invention concerne un polymère antimicrobien destiné à être utilisé dans un implant ophtalmique qui comprend au moins un monomère antimicrobien ; et au moins un autre monomère choisi parmi un monomère acrylique, de silicone, de vinyle et de collagène.
EP18903224.6A 2018-01-31 2018-01-31 Polymère antimicrobien destiné à être utilisé dans des implants ophtalmiques Pending EP3745998A4 (fr)

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
PCT/US2018/016257 WO2019152023A1 (fr) 2018-01-31 2018-01-31 Polymère antimicrobien destiné à être utilisé dans des implants ophtalmiques

Publications (2)

Publication Number Publication Date
EP3745998A1 true EP3745998A1 (fr) 2020-12-09
EP3745998A4 EP3745998A4 (fr) 2021-09-01

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Family Applications (2)

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EP18903224.6A Pending EP3745998A4 (fr) 2018-01-31 2018-01-31 Polymère antimicrobien destiné à être utilisé dans des implants ophtalmiques
EP19780818.1A Active EP3850018B1 (fr) 2018-01-31 2019-02-14 Lentilles de contact antimicrobiennes

Family Applications After (1)

Application Number Title Priority Date Filing Date
EP19780818.1A Active EP3850018B1 (fr) 2018-01-31 2019-02-14 Lentilles de contact antimicrobiennes

Country Status (5)

Country Link
US (1) US20210077249A1 (fr)
EP (2) EP3745998A4 (fr)
JP (2) JP7560865B2 (fr)
CN (2) CN111670020A (fr)
WO (2) WO2019152023A1 (fr)

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US4218554A (en) * 1978-10-11 1980-08-19 Foley William M Jr Process for preparing hydrogel contact lenses containing quaternary ammonium salts
AU546039B2 (en) * 1982-05-08 1985-08-08 Menicon Co., Ltd Oxygen permeable hard contact lens
JP3357094B2 (ja) * 1991-10-18 2002-12-16 株式会社クラレ 抗菌性重合性組成物、それより得られるポリマーおよび用品
EP0537774B1 (fr) * 1991-10-18 1998-01-07 Kuraray Co., Ltd. Composition antimicrobienne polymérisable, le polymère et article fabriqué à partir de ce polymère
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WO2019152023A1 (fr) 2019-08-08
CN111670020A (zh) 2020-09-15
EP3850018A4 (fr) 2021-11-17
JP7560865B2 (ja) 2024-10-03
JP2021513107A (ja) 2021-05-20
JP7408153B2 (ja) 2024-01-05
EP3850018A1 (fr) 2021-07-21
WO2019194903A1 (fr) 2019-10-10
EP3745998A4 (fr) 2021-09-01
EP3850018C0 (fr) 2023-08-23
US20210077249A1 (en) 2021-03-18
CN111836839A (zh) 2020-10-27
EP3850018B1 (fr) 2023-08-23

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