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
  • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
  • A61L27/28—Materials for coating prostheses
  • A61L27/34—Macromolecular 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
  • 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
  • A61L31/043—Proteins; Polypeptides; Degradation products thereof
  • A61L31/047—Other specific proteins or polypeptides not covered by A61L31/044 - A61L31/046
• • 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
  • 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
  • A61L2300/20—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing organic materials
  • A61L2300/252—Polypeptides, proteins, e.g. glycoproteins, lipoproteins, cytokines
• • 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
  • A61L2430/20—Materials or treatment for tissue regeneration for reconstruction of the heart, e.g. heart valves

Definitions

• the application is generally directed to systems and methods of preparing bioprosthetic tissue, and more specifically to antimicrobial peptide treatment of prosthetic devices and delivery systems.
• Prosthetic valve endocarditis is a serious complication of valve replacement.
• Prosthetic valve endocarditis is defined as an infection occurring in a prosthetic heart valve with overall incidence of 0.32 to 1.2% per patient year and cumulative risk of 5% at 10 years.
• surgery for infectious endocarditis was associated with a mortality of 25%-6O%.
• PVE is defined as early if occurring within 12 months of valve replacement and late if greater than 12 months have elapsed. Most cases are caused by Staphylococcus epidermidis and aureus, followed by Streptococcus. Early PVE is often due to methicillin- resistant Staphylococcus epidermidis, gram-negative bacilli, fungi, and other HACEK group organisms (Haemophilus, Actinobacillus, Cardiobacterium, Eikinella, Kingella), suggesting nosocomial infection.
• the disclosure is generally directed to systems and methods to treat bioprosthetic tissue, polymer-based leaflets, prosthetic heart valves, and/ or delivery devices with antimicrobial peptides and polypeptides for preclinical or clinical use.
• a method is for preparing antimicrobial tissue or polymer.
• the method treats bioprosthetic tissue or polymer with an antimicrobial peptide solution.
• the method also prepares the bioprosthetic tissue or polymer for preclinical or clinical use.
• the antimicrobial peptide solution comprises a lysine- rich peptide, an arginine-rich peptide, a proline-rich peptide, a histidine rich peptide, or a proline rich peptide.
• the antimicrobial peptide solution comprises a peptide that comprises at least one hydrophilic block and at least one hydrophobic block. [0009] In some implementations, the antimicrobial peptide solution comprises a peptide that comprises at least one positively charged block and at least one negatively charged block.
• the treating of the bioprosthetic tissue or polymer comprises spray coating, brush coating, or spin coating the bioprosthetic tissue or polymer with the antimicrobial peptide solution.
• the treating of the bioprosthetic tissue or polymer comprises dipping the bioprosthetic tissue or polymer with the antimicrobial peptide solution.
• the treating of the bioprosthetic tissue or polymer comprises immersing the bioprosthetic tissue or polymer in the antimicrobial peptide solution.
• bioprosthetic tissue is fixed utilizing a biodegradable crosslinker, such as (for example) an enzymatic crosslinker, which can increase biocompatibility of the tissue.
• Enzymatic crosslinkers include transglutaminases (e.g., factor XIII) and oxidoreductases (e.g., tyrosinases, laccases with peroxidases, and lysyl oxidases with amine oxidases).
• transglutaminases e.g., factor XIII
• oxidoreductases e.g., tyrosinases, laccases with peroxidases, and lysyl oxidases with amine oxidases.
• a precipitating reagent is utilized.
• Precipitating reagents include (but are not limited to) methanol, ethanol, propanol, and acetone.
• the appropriate fixation methodology and reagents utilized can vary and are often dependent on the endproduct. For instance, when fixed (or cross-linked) tissues are to be utilized for a clinical application, it may be desired to use a less toxic fixative or a fixative that can be rendered less toxic with a post-fixation procedure.
• AMP treatment of tissue or polymer is performed in a solution.
• the AMP solution comprises glycerol, ethanol, and water.
• an AMP solution is buffered to maintain a pH between and 6.5 and 8.0, and in some instances a pH between about 7.0 and 7.5, which may confer a benefit to stabilize the aqueous environment and the bioprosthetic tissue.
• Polypeptides form long range interactions with pericardium collagen molecules since their chemistries are similar therefore delamination of the coating was never observed.
• buffer salt including (but not limited to) phosphate buffered solution (PBS), potassium chloride (KCL), monobasic potassium phosphate (KH 2 PO 4 ), dibasic potassium phosphate (K2HPO4), sodium chloride (NaCl) including isotonic saline, potassium bromide (KBr), sodium bromide (NaBr), calcium chloride (CaCl 2 ), HEPES, MES, MOPS, HEPPs, HEPBS, and Tris-HCl.
• PBS phosphate buffered solution
• KCL potassium chloride
• KH 2 PO 4 monobasic potassium phosphate
• K2HPO4 dibasic potassium phosphate
• NaCl sodium chloride
• KCL potassium bromide
• NaBr sodium bromide
• CaCl 2 calcium chloride
• HEPES MES
• MOPS HEPPs
• HEPBS Tris-HCl
• prosthetic tissue or polymer-based leaflets are prepared for storage, which may help with long-term preservation.
• Storage can be dry storage or wet storage.
• Wet storage methods include storing the tissue or polymer within a solution, such as (for example) a fixation buffer (e.g., glutaraldehyde buffer) or propylene oxide in water.
• Dry storage methods include treating a tissue or polymer with a solution inclusive of a biocompatible molecule for a period of time, which can allow the components of the solution to equilibrate within the tissue or polymer. The tissue or polymer is then stored free of liquids, except for the components of the aqueous solution equilibrated therein.
• Biocompatible molecules to be included within a solution for dry storage include (but are not limited to) glycerol, propylene glycol, polyethylene glycol, and saccharides.
• Solvents for dry storage include (but are not limited) aqueous based solvents, alcohol-based solvents, any other biocompatible solvent, and any solvent mixture thereof.
• aqueous based solvents include (but are not limited) aqueous based solvents, alcohol-based solvents, any other biocompatible solvent, and any solvent mixture thereof.
• U.S. Patent No. 6,534,004 by Chen et al. U.S. Patent No. 8,007,992 by Tian et al.
• U.S. Patent No. 10,383,978 by Dong et al. the disclosures of which are each incorporated herein by reference for all purposes.
• prosthetic tissue is sterilized, which can be performed using gamma irradiation, gas plasma, aldehydes, ethylene oxide, and/or e-be
• a medical device is any prosthetic device for the purpose of implanting into a recipient.
• Recipients include (but are not limited to) patients, animal models, cadavers, or anthropomorphic phantoms.
• a medical device can be a tissue patch, a medical vessel, a conduit, a closure device, a prosthetic heart valve including (but not limited to) aortic, mitral, tricuspid and pulmonary prosthetic valves, or a delivery system.
• a number of treatments can be performed on bioprosthetic tissue to prepare it for clinical or preclinical use, including (but not limited to) tissue fixation, tissue stabilization, bioburden reduction, AMP treatment, cutting and shaping of tissue, assembly into a medical device, preservation, sterilization, and any set of combinations thereof.
• the heart valve 301 can be a transcatheter heart valve that can be crimped into a confined profile such that it can be used in a transcatheter delivery system to implant the valve.
• heart valve 301 comprises a set of leaflets 303 to perform the valve function, a frame 305 for supporting the leaflets, and an inner cover 307 to ensure proper blood flow through the valve.
• the heart valve can further comprise an outer skirt to mitigate perivalvular leakage and/or protect the frame from the surrounding tissue or protect the surrounding tissue from the frame.
• the valve can further comprise an anchor or other means for securing the valve at the site of implantation.
• Valvular prosthetics can be assembled with AMP treated bioprosthetic tissue or polymer-based leaflets. Any methods for assembly of a prosthetic valve can be utilized.
• AMP treated bioprosthetic tissue or polymer can be shaped into a leaflet via cutting, laser ablation, or any method to formulate a leaflet 401 having have an extended cusp edge 403 and an attachment edge 405 (Fig. 4A).
• the attachment edge can be utilized to attach leaflets together into a leaflet assembly 410 (Fig. 4B) and/or attach the leaflets to an inner wall of a valvular conduit (e.g., inner cover).
• the assembled leaflets, along with the inner wall of the conduit provided a means for unidirectional blood flow. When the valve is closed, the cusp edges come together and form a seal, preventing retrograde blood flow.
• Assembled transcatheter heart valve prosthetics can be utilized with a delivery system to deliver a heart valve to the site of implantation.
• An exemplary delivery system is provided in Fig. 5.
• Delivery system 501 is adapted to deliver a prosthetic heart valve 503, which is secured to the system.
• Delivery system 501 includes a steerable flex catheter 505 for guiding the distal end of the delivery system and an inner catheter 507 for assisting with extraction and installation of the prosthetic heart valve.
• Inner catheter 507 can be a balloon catheter for expanding the prosthetic heart valve at the site of implantation.
• prosthetic heart valve 503 is in a crimped state to reduce the profile of the prosthetic such that it can traverse through the vasculature of the recipient.
• a nose piece 509 can be provided at the proximal end of delivery system 501, which can have a tapered contour to better traverse through the vasculature and facilitate advancement of the delivery system.
• Delivery system 501 can further include a handle 511 and shaft extending from the handle and in connection with flex catheter 505 and inner catheter 507.
• Handle 511 can include a side arm 513 having an internal passage for fluidic communication with one or more internal lumens, which can provide fluidic connection to expand a balloon or provide other capabilities for valve installation.
• Handle 511 can also include a rotatable member 515 or other means for advancing flex catheter 505 and inner catheter 507.
• AMPs especially components that come into contact or enter within the recipient. Accordingly, various components can be spray coated and/or dipped with AMPs and then assembled into the prosthetic. Components that can be treated can include any component of the prosthetic or delivery system.
• the frame of the valve is treated with AMPs.
• the inner wall conduit e.g., inner cover
• the outer skirt is treated with AMPs.
• an anchor is treated with AMPs.
• components for securing the various components together are treated with AMPs, such as sutures which can be used to attach leaflets, a cover and/or a skirt to one another and/or to the frame of the valve.
• AMP treatment is performed directly before, concurrently with, or immediately after sterilization as part of the sterilization process.
• particular components of a delivery system are treated with AMPs to provide particular benefits. For instance, components that would come in contact with the vasculature (e.g, nose cone, flex catheter, inner catheter, etc.) are treated with AMPs.
• a balloon for expanding a heart valve prosthetic or other tubular prosthetic is treated with AMPs.
• the balloon When a balloon is coated with AMPs, the balloon can be used as a means to treat the interior luminal walls of a tubular prosthetic (e.g., heart valve). To do so, when the balloon is expanded and pressed upon the luminal walls of tubular prosthetic, the AMPs can be transferred onto the walls. This procedure can be done during or after installation of the tubular prosthetic.
• a tubular prosthetic e.g., heart valve
• Process 600 can begin by obtaining (601) a prosthetic or delivery system.
• the prosthetic or delivery system is fully assembled.
• the prosthetic or the delivery system is partially assembled.
• the prosthetic can be a medical vessel, a conduit, a closure device, or a prosthetic heart valve including (but not limited to) aortic, mitral, tricuspid and pulmonary prosthetic valves.
• the delivery system can be a system for delivering a prosthetic to the implantation site within the recipient.
• Process 600 also treats (603) the prosthetic or delivery system (or a component thereof) with AMPs.
• the prosthetic or the delivery system can be spray coated, dipped, immersed, and/or perfused utilizing an AMP solution. Any appropriate treatment can be utilized.
• the prosthetic or the delivery system is spray coated with AMPs.
• the prosthetic or the delivery system is dipped in an AMP solution.
• the prosthetic or the delivery system is immersed in an AMP solution.
• the prosthetic or delivery system is perfused with an AMP solution.
• AMP treatment of the prosthetic or the delivery system is performed in an aqueous solution.
• an aqueous solution is buffered to maintain a pH below about 8.5, and in some instances a pH between about 7.5 and 8.5, which may confer a benefit to stabilize the aqueous environment and the bioprosthetic tissue.
• Process 600 also prepares 605 the prosthetic or the delivery system for clinical or preclinical use. The exact preparation depends on the clinical or preclinical application. In some instances, the prosthetic or the delivery system is used in treatment of patient. In some instances, the prosthetic or the delivery system used in preclinical applications, such as (for example) training procedures on cadavers, animal models, or anthropomorphic phantoms.
• a number of measures can be taken to prepare the prosthetic or the delivery system for clinical or preclinical use.
• the prosthetic or the delivery system is prepared for storage, which may help with long-term preservation.
• Storage can be dry storage or wet storage.
• Wet storage methods include storing the prosthetic or the delivery system within a solution, such as (for example) a fixation buffer (e.g., glutaraldehyde buffer) or propylene oxide in water.
• Dry storage methods include treating the prosthetic or the delivery system with a solution inclusive of a biocompatible molecule for a period of time, which can allow the components of the solution to equilibrate within the prosthetic or the delivery system.
• Biocompatible molecules to be included within a solution for dry storage include (but are not limited to) glycerol, propylene glycol, polyethylene glycol, and saccharides.
• Solvents for dry storage include (but are not limited) aqueous based solvents, alcohol-based solvents, any other biocompatible solvent, and any solvent mixture thereof. For more description of dry storage methods, see U.S. Patent No. 6,534,004 by Chen et al., U.S. Patent No. 8,007,992 by Tian et al., and U.S.
• the prosthetic or the delivery system is sterilized, which can be performed using gamma irradiation, gas plasma, aldehydes, ethylene oxide, and/or e-beam. After preparation, the prosthetic or the delivery system can be stored within a container, which can be hermetically sealed or otherwise kept sterile.
• AMP treatment and preparation of a prosthetic or a delivery system are described above, one of ordinary skill in the art can appreciate that various steps of the process can be performed in different orders and that certain steps may be optional according to some aspects of the description. As such, it should be clear that the various steps of the process could be used as appropriate to the requirements of specific applications. Furthermore, any of a variety of processes for AMP treatment and preparation of a prosthetic or a delivery system appropriate to the requirements of a given application can be utilized in accordance with various aspects of the description.
• prosthetic valves or delivery systems are disclosed herein, and any combination of these options can be made unless specifically excluded.
• any of the methods disclosed can be used with any type of valve, and/or any delivery system, even if a specific combination is not explicitly described.
• the different constructions and features of prosthetics and delivery systems can be mixed and matched, such as by combining any feature even if not explicitly disclosed.
• individual components of the disclosed systems can be combined unless mutually exclusive or physically impossible.

Landscapes

• Health & Medical Sciences (AREA)
• Life Sciences & Earth Sciences (AREA)
• General Health & Medical Sciences (AREA)
• Chemical & Material Sciences (AREA)
• Veterinary Medicine (AREA)
• Medicinal Chemistry (AREA)
• Public Health (AREA)
• Epidemiology (AREA)
• Animal Behavior & Ethology (AREA)
• Transplantation (AREA)
• Oral & Maxillofacial Surgery (AREA)
• Dermatology (AREA)
• Heart & Thoracic Surgery (AREA)
• Surgery (AREA)
• Vascular Medicine (AREA)
• Engineering & Computer Science (AREA)
• Biomedical Technology (AREA)
• Molecular Biology (AREA)
• Materials For Medical Uses (AREA)
• Prostheses (AREA)

Applications Claiming Priority (2)

Publications (1)

Family

ID=89164459

Family Applications (1)

Country Status (3)

Family Cites Families (12)

• 2023
  • 2023-11-07 EP EP23821452.2A patent/EP4626496A1/de active Pending
  • 2023-11-07 CN CN202380083113.XA patent/CN120322258A/zh active Pending
  • 2023-11-07 WO PCT/US2023/078983 patent/WO2024118297A1/en not_active Ceased

Also Published As

Similar Documents

Legal Events