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
  • 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
  • A61L31/14—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
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07K—PEPTIDES
  • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
  • C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
  • C07K14/46—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
  • C07K14/47—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals
  • C07K14/4701—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals not used
  • C07K14/4723—Cationic antimicrobial peptides, e.g. defensins
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K38/00—Medicinal preparations containing peptides
• • 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
  • A61L2300/25—Peptides having up to 20 amino acids in a defined sequence
• • 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
  • A61L2400/00—Materials characterised by their function or physical properties
  • A61L2400/18—Modification of implant surfaces in order to improve biocompatibility, cell growth, fixation of biomolecules, e.g. plasma treatment

Definitions

• a surface of the device may comprise a polymer, for example a hydrogel, a silicon hydrogel, a polymer or copolymer of 2-hydroxyethylmethacrylate, silicon rubber, polyurethane, polypropylene, polyethylene, polyacrylamide, polytetrafluoroethylene (Teflon), a biodegradable polymer, such as poly-lactide, or combinations thereof
• a polymer for example a hydrogel, a silicon hydrogel, a polymer or copolymer of 2-hydroxyethylmethacrylate, silicon rubber, polyurethane, polypropylene, polyethylene, polyacrylamide, polytetrafluoroethylene (Teflon), a biodegradable polymer, such as poly-lactide, or combinations thereof
• the present disclosure provides a method for encouraging or stimulating tissue adhesion to a surface, the method comprising attaching to the surface, or coating the surface with, a peptide that is antimicrobial and comprises a cell recognition and/or adhesion moiety.
• the surface is the surface of a device, such as a medical device.
• the bacteria may be Gram-negative or Gram-positive bacteria.
• the bacteria are Staphylococcus spp., such as S. aureus, or Pseudomonas spp., such as P. aeruginosa.
• FIG. 1 Representative images of adhesion of human epithelial cells to Cys-Mel-4 coated fluorinated ethylene propylene (FEP).
• FEP fluorinated ethylene propylene
• A unmodified FEP
• B poly(heptylamineamine) surface coating
• C process control
• D surface coated with mammalian cell recognition and/or adhesion motif (amino acid sequence GRGDSPC) (positive control)
• E surface coated with Cys-Mel-4
• F surface coated with negative control peptide.
• Examples 1 to 5 The inventors have found (Examples 1 to 5) that the addition of a cell recognition and/or adhesion moiety to an antimicrobial peptide produces a peptide that is bifunctional, i.e. the addition of the cell recognition and/or adhesion moiety to the antimicrobial peptide retains the antimicrobial activity and facilitates cell recognition and/or adhesion.
• the peptides of the first aspect may be further modified to facilitate attachment of the peptide to a surface, for example, by the introduction of a thiol functional group, such as a thiol-containing residue, into the peptide.
• a thiol functional group such as a thiol-containing residue
• the thiol-containing residue may be cysteine.
• the thiol functional group or residue that comprises a thiol functional group may be introduced into the peptide at any position, and in embodiments of the disclosure is introduced at the C-terminus or at the N-terminus of the peptide. In particular embodiment a cysteine residue is introduced at the N-terminus of the peptide.
• the cell recognition and/or adhesion moiety may be incorporated at one or more positions within the peptide sequence or at the C- tenninus or the N-tenriinus.
• the peptide moiety is located at the C- terrninus of the peptide having antimicrobial activity.
• the peptide moiety is located at the N-terminus of the peptide having antimicrobial activity.
• the peptide moiety is located between the C-terminus and the N-terminus of the peptide having antimicrobial activity.
• Exemplary species include but are not limited to Staphylococcus aureus, methicillin-resistant Staphylococcus aureus (MRSA), Staphylococcus epidermidis, coagulase negative staphylococci, Enterococcus faecalis, Enterococcus faecium including vancomycin-resistant Enterococcus faecium, Streptococcus pneumoniae, Klebsiella pneumoniae, Haemophilus influenzae, Pseudomonas aeruginosa, Escherichia coli, Salmonella enterica, Salmonella typhi, Bacillus cereus, and Listeria monocytogenes.
• MRSA methicillin-resistant Staphylococcus aureus
• Staphylococcus epidermidis Staphylococcus epidermidis
• coagulase negative staphylococci Enterococcus faecalis
• Enterococcus faecium including
• the peptides disclosed herein are attached to a surface, for example the surface of a device, such as a medical device.
• the medical device may be, for example, a contact lens, a corneal only or inlay device, fluid collection bag, sensor, hydrogel bandage, tubing, stent, heart valve, an implant, such as a hearing implant, a knee implant, a hip implant, an implantable electrode, an implantable neuroprosthetic electrode array (such as those manufactured by Cochlear), a catheter (such as an indwelling catheter) or carrier for antibiotic, diagnostic or therapeutic agents.
• HEMA-MMA polymer hydroxyethyl methacrylate- methyl methacrylate
• EDC zero-length crosslinker l-ethyl-3-[3- dimethylaminopropyljcarbodiimide hydrochloride (EDC) was used to crosslink carboxylic acid (COOH) groups on the polymer and amine (NH2) groups of the peptides.
• COOH carboxylic acid
• NH2 amine
• L929 cells were established at low density in 35 mm polystyrene petri dishes. After 24 hours, medium was replaced with fresh medium containing the test solution (25% test solution, 75% fresh medium). Test peptides were dissolved in PBSas. After a further 48 hours, cells were stained with trypan blue, which is excluded from viable cells, and counted by microscopy. Cytotoxicity is indicated by a greater than 30% reduction in viable cell numbers, as compared to non-challenged cultures. Experiments were conducted in accordance with ISO 10993-5, Biological evaluation of medical devices - Part 5: Tests for in vitro cytotoxicity.

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• Health & Medical Sciences (AREA)
• Life Sciences & Earth Sciences (AREA)
• Chemical & Material Sciences (AREA)
• Medicinal Chemistry (AREA)
• General Health & Medical Sciences (AREA)
• Veterinary Medicine (AREA)
• Molecular Biology (AREA)
• Organic Chemistry (AREA)
• Public Health (AREA)
• Animal Behavior & Ethology (AREA)
• Biomedical Technology (AREA)
• Epidemiology (AREA)
• Engineering & Computer Science (AREA)
• Zoology (AREA)
• Oral & Maxillofacial Surgery (AREA)
• Toxicology (AREA)
• Surgery (AREA)
• Gastroenterology & Hepatology (AREA)
• Biochemistry (AREA)
• Biophysics (AREA)
• Genetics & Genomics (AREA)
• Proteomics, Peptides & Aminoacids (AREA)
• Heart & Thoracic Surgery (AREA)
• Dermatology (AREA)
• Vascular Medicine (AREA)
• Transplantation (AREA)
• Communicable Diseases (AREA)
• Oncology (AREA)
• Chemical Kinetics & Catalysis (AREA)
• General Chemical & Material Sciences (AREA)
• Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
• Pharmacology & Pharmacy (AREA)
• Materials For Medical Uses (AREA)
• Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
• Peptides Or Proteins (AREA)

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Cited By (3)

Citations (5)

• 2013
  • 2013-10-11 WO PCT/AU2013/001176 patent/WO2014056039A1/fr not_active Ceased

Patent Citations (5)

Non-Patent Citations (1)

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