WO2014133543A1 - Valvule prothétique en deux parties - Google Patents

Valvule prothétique en deux parties Download PDF

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Publication number
WO2014133543A1
WO2014133543A1 PCT/US2013/028611 US2013028611W WO2014133543A1 WO 2014133543 A1 WO2014133543 A1 WO 2014133543A1 US 2013028611 W US2013028611 W US 2013028611W WO 2014133543 A1 WO2014133543 A1 WO 2014133543A1
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WO
WIPO (PCT)
Prior art keywords
valve
growth factor
tissue
extracellular matrix
piece
Prior art date
Application number
PCT/US2013/028611
Other languages
English (en)
Inventor
Robert G. Matheny
Zachary REINHARDT
Original Assignee
Cormatrix Cardiovascular, 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 Cormatrix Cardiovascular, Inc. filed Critical Cormatrix Cardiovascular, Inc.
Priority to AU2013379748A priority Critical patent/AU2013379748A1/en
Priority to EP13861485.4A priority patent/EP2809264A4/fr
Priority to PCT/US2013/028611 priority patent/WO2014133543A1/fr
Priority to JP2015560150A priority patent/JP2016512989A/ja
Publication of WO2014133543A1 publication Critical patent/WO2014133543A1/fr
Priority to HK14112553.8A priority patent/HK1198904A1/xx

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Classifications

    • 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
    • A61F2/04—Hollow or tubular parts of organs, e.g. bladders, tracheae, bronchi or bile ducts
    • A61F2/06—Blood vessels
    • 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
    • A61F2/24—Heart valves ; Vascular valves, e.g. venous valves; Heart implants, e.g. passive devices for improving the function of the native valve or the heart muscle; Transmyocardial revascularisation [TMR] devices; Valves implantable in the body
    • A61F2/2412—Heart valves ; Vascular valves, e.g. venous valves; Heart implants, e.g. passive devices for improving the function of the native valve or the heart muscle; Transmyocardial revascularisation [TMR] devices; Valves implantable in the body with soft flexible valve members, e.g. tissue valves shaped like natural valves
    • 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
    • A61F2/24—Heart valves ; Vascular valves, e.g. venous valves; Heart implants, e.g. passive devices for improving the function of the native valve or the heart muscle; Transmyocardial revascularisation [TMR] devices; Valves implantable in the body
    • A61F2/2475—Venous valves
    • 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
    • A61L27/36—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix
    • A61L27/3604—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix characterised by the human or animal origin of the biological material, e.g. hair, fascia, fish scales, silk, shellac, pericardium, pleura, renal tissue, amniotic membrane, parenchymal tissue, fetal tissue, muscle tissue, fat tissue, enamel
    • A61L27/362—Skin, e.g. dermal papillae
    • 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
    • A61L27/36—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix
    • A61L27/3604—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix characterised by the human or animal origin of the biological material, e.g. hair, fascia, fish scales, silk, shellac, pericardium, pleura, renal tissue, amniotic membrane, parenchymal tissue, fetal tissue, muscle tissue, fat tissue, enamel
    • A61L27/3625—Vascular tissue, e.g. heart valves
    • 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
    • A61L27/36—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix
    • A61L27/3604—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix characterised by the human or animal origin of the biological material, e.g. hair, fascia, fish scales, silk, shellac, pericardium, pleura, renal tissue, amniotic membrane, parenchymal tissue, fetal tissue, muscle tissue, fat tissue, enamel
    • A61L27/3629—Intestinal tissue, e.g. small intestinal submucosa
    • 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
    • A61L27/36—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix
    • A61L27/3604—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix characterised by the human or animal origin of the biological material, e.g. hair, fascia, fish scales, silk, shellac, pericardium, pleura, renal tissue, amniotic membrane, parenchymal tissue, fetal tissue, muscle tissue, fat tissue, enamel
    • A61L27/3633—Extracellular matrix [ECM]
    • 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
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/06—Antiarrhythmics
    • 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
    • A61F2250/00—Special features of prostheses classified in groups A61F2/00 - A61F2/26 or A61F2/82 or A61F9/00 or A61F11/00 or subgroups thereof
    • A61F2250/0058—Additional features; Implant or prostheses properties not otherwise provided for
    • A61F2250/006—Additional features; Implant or prostheses properties not otherwise provided for modular
    • A61F2250/0063—Nested prosthetic parts
    • 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 present invention generally relates to prosthetic valves for replacing defective cardiovascular valves. More particularly, the present invention relates to two-piece prosthetic valves for replacing defective aortic, pulmonary, mitral, tricuspid and/or peripheral venous valves.
  • the human heart has four valves that control blood flow circulating through the human body.
  • the mitral valve located between the left atrium and the left ventricle
  • the aortic valve located between the left ventricle and the aorta. Both of these valves direct oxygenated blood from the lungs into the aorta for distribution through the body.
  • the peripheral venous system also includes a number of valves that prevent retrograde blood flow. By preventing retrograde blood flow, the valves found throughout the venous system assist the flow of blood through the veins and returning to the heart.
  • the mitral valve has two leaflets and the tricuspid valve has at least two, preferably three leaflets.
  • the aortic and pulmonary valves have normally at least two, preferably three leaflets, also often referred to as "cusps" because of their half-moon like appearance.
  • Venous valves are usually of the bicuspid type, with each cusp or leaflet forming a reservoir for blood, which, under pressure, forces the free edges of the cusps together to permit mostly antegrade blood flow to the heart.
  • venous blood flow is against gravity while a person is standing, incompetent or destroyed venous valves can cause significant medical problems in the legs, ankles, and feet.
  • Valve diseases are typically classified into two major categories; stenosis and insufficiency. In the case of a stenosis, the native valve does not open properly, whereby insufficiency represents the opposite effect showing deficient closing properties.
  • Insufficiency of the inlet (atrioventricular) tricuspid valve to the right ventricle of the heart results in regurgitation of blood back into the right atrium, which, serving to receive blood flow returning in the veins from the entire body, then results in turn in suffusion and swelling (edema) of all the organs, most notably in the abdomen and extremities, insufficient forward conduction of blood flow from the right ventricle into the lungs causing compromise of pulmonary function, and ultimately pump failure of the right heart.
  • right heart failure a condition that leads to incapacity and possibly to death if progressive and uncorrected.
  • This condition can affect the deep veins of the body , commonly the lower extremities or pelvis, or the superficial veins of the lower extremities in particular, leading to progressive expansion of the veins and further valvular incompetence, a condition known as varicose veins.
  • Heart valve dysfunctions typically include reparation of the diseased heart valve with preservation of the patient's own valve or replacement of the valve with a mechanical or bioprosthetic valve (i.e. "tissue” valve), i.e. a prosthetic valve.
  • tissue i.e. a mechanical or bioprosthetic valve
  • aortic heart valve it is frequently necessary to introduce a heart valve replacement.
  • a major drawback associated with most one-piece prosthetic valves is that the valves are typically sized and configured for replacement of a defined valve, i.e. aortic, pulmonary, mitral, tricuspid or peripheral venous valve.
  • a sizable number of one-piece prosthetic valves must thus be produced to accommodate replacement of diseased or defective aortic, pulmonary, mitral, tricuspid or peripheral venous valves.
  • bioprosthetic valves also requires a great deal of skill and concentration given the delicate nature of the native cardiovascular tissue and the spatial constraints of the surgical field. It is also critical to achieve a secure and reliable attachment of the valve to host cardiovascular tissue.
  • the tissue valve includes a sewing ring that can be employed to suture the ends of the valve to the annulus of the cardiovascular vessel.
  • the present invention is directed to two-piece prosthetic valves having first and second members, a first end of the first member being sized and configured to receive a second end of the second member therein, the second end of the second member being secured to the first member at at least one commissure connection point to form at least one leaflet therein.
  • the second end of the second member is secured to the first member at two commissure connection points to form two leaflets therein.
  • the second end of the second member is secured to the first member at three commissure connection points to form three leaflets therein.
  • the first and second valve members comprise an extracellular matrix (ECM) material.
  • ECM extracellular matrix
  • the ECM material can be derived from a variety of mammalian tissue sources, including, without limitation, small intestine submucosa (SIS), urinary bladder submucosa (UBS), stomach submucosa (SS), central nervous system tissue, epithelium of mesodermal origin, i.e.
  • mesothelial tissue dermal extracellular matrix, subcutaneous extracellular matrix,
  • the ECM material can also comprise collagen from mammalian sources.
  • the ECM material can also be derived from basement membrane of mammalian tissue/organs, including, without limitation, urinary basement membrane (UBM), liver basement membrane (LBM), and amnion, chorion, allograft pericardium, allograft acellular dermis, amniotic membrane, Wharton's jelly, and combinations thereof.
  • UBM urinary basement membrane
  • LBM liver basement membrane
  • amnion amnion
  • chorion allograft pericardium
  • allograft acellular dermis amniotic membrane
  • Wharton's jelly and combinations thereof.
  • Additional sources of mammalian basement membrane include, without limitation, spleen, lymph nodes, salivary glands, prostate, pancreas and other secreting glands.
  • the ECM material can also be derived from other sources, including, without limitation, collagen from plant sources and synthesized extracellular matrices, i.e. cell cultures.
  • the first and/or second valve members include at least one pharmacological agent, i.e. an agent that is capable of producing a desired biological effect in vivo, e.g., stimulation or suppression of cell division, stimulation or suppression of apoptosis, stimulation or suppression of an immune response, anti-bacterial activity, etc.
  • pharmacological agent i.e. an agent that is capable of producing a desired biological effect in vivo, e.g., stimulation or suppression of cell division, stimulation or suppression of apoptosis, stimulation or suppression of an immune response, anti-bacterial activity, etc.
  • the pharmacological agent comprises an anti-inflammatory agent.
  • the pharmacological agent comprises a statin, i.e. a HMG-CoA reductase inhibitor.
  • the two-piece prosthetic valves include at least one anchoring mechanism.
  • the anchoring mechanism comprises at least one reinforcing ring or band that is positioned and secured at a desired position on or in the valve.
  • the anchoring mechanism comprises at least two reinforcing rings that are positioned and secured at desired positions, e.g. proximal and distal ends, on or in the valve.
  • the anchoring mechanisms are designed and configured to position the two-piece valves proximate the wall of a vessel (i.e. host tissue thereof), and maintain contact therewith, for a predetermined temporary support time period.
  • the support time period is within the process of tissue regeneration.
  • the two-piece prosthetic valves of the invention provide numerous advantages compared to prior art prosthetic valves. Among the advantages are the following:
  • cardiovascular vessels including aortic, pulmonary, mitral, tricuspid and/or peripheral venous vessels.
  • FIGURE 1 is a perspective view of one embodiment of first and second pre- assembled valve members, in accordance with the invention.
  • FIGURE 2 is a side plan, sectional view of an assembled two-piece prosthetic valve, in accordance with the invention.
  • FIGURE 3 is a perspective view of the two-piece prosthetic valve shown in FIGURE 2, showing one embodiment of commissure connection points, in accordance with the invention
  • FIGURE 4 is a front (or end) plan view of one embodiment of a two-piece prosthetic valve having three leaflets formed therein, in accordance with the invention
  • FIGURE 5 is a front plan view of another embodiment of a two-piece prosthetic valve having one leaflet formed therein, in accordance with the invention.
  • FIGURE 6 is a front plan view of another embodiment of a two-piece prosthetic valve having two leaflets formed therein, in accordance with the invention.
  • anchoring mechanism and “anchor”, as used herein in connection with some embodiments of the two-piece anchored valves, mean a temporary structure that is configured and employed to "temporarily” position the valve proximate vessel tissue.
  • the anchoring mechanisms are designed and configured to temporarily position tissue valves proximate a recipient's cardiovascular tissue for a predetermined period of time, which, in some embodiments, is preferably within the process of new tissue regeneration.
  • extracellular matrix and “ECM material” are used interchangeably herein, and mean and include a collagen-rich substance that is found in between cells in mammalian tissue, and any material processed therefrom, e.g. decellularized ECM.
  • the ECM material can be derived from a variety of mammalian tissue sources, including, without limitation, small intestine submucosa (SIS), urinary bladder submucosa (UBS), stomach submucosa (SS), central nervous system tissue, epithelium of mesodermal origin, i.e. mesothelial tissue, dermal extracellular matrix, subcutaneous extracellular matrix, gastrointestinal extracellular matrix, i.e.
  • SIS small intestine submucosa
  • UBS urinary bladder submucosa
  • SS stomach submucosa
  • central nervous system tissue epithelium of mesodermal origin, i.e. mesothelial tissue, dermal extracellular matrix, subcutaneous extracellular matrix, gastrointestinal
  • the ECM material can also comprise collagen from mammalian sources.
  • UBS urinary bladder submucosa
  • SIS small intestine submucosa
  • SS stomach submucosa
  • the ECM material can also be derived from basement membrane of mammalian tissue/organs, including, without limitation, urinary basement membrane (UBM), liver basement membrane (LBM), and amnion, chorion, allograft pericardium, allograft acellular dermis, amniotic membrane, Wharton's jelly, and combinations thereof.
  • UBM urinary basement membrane
  • LBM liver basement membrane
  • amnion amnion
  • chorion allograft pericardium
  • allograft acellular dermis amniotic membrane
  • Wharton's jelly and combinations thereof.
  • Additional sources of mammalian basement membrane include, without limitation, spleen, lymph nodes, salivary glands, prostate, pancreas and other secreting glands.
  • the ECM material can also be derived from other sources, including, without limitation, collagen from plant sources and synthesized extracellular matrices, i.e. cell cultures.
  • angiogenesis means a physiologic process involving the growth of new blood vessels from pre-existing blood vessels.
  • neovascularization means and includes the formation of functional vascular networks that can be perfused by blood or blood components.
  • Neovascularization includes angiogenesis, budding angiogenesis, intussuceptive angiogenesis, sprouting angiogenesis, therapeutic angiogenesis and vasculo genesis.
  • pharmacological agent means and include an agent, drug, compound, composition of matter or mixture thereof, including its formulation, which provides some therapeutic, often beneficial, effect.
  • mice such as mice, rats and guinea pigs; fish; reptiles; zoo and wild animals; and the like.
  • pharmacological agent thus mean and include, without limitation, antibiotics, anti-arrhythmic agents, anti-viral agents, analgesics, steroidal anti-inflammatories, non-steroidal antiinflammatories, anti-neoplastics, anti-spasmodics, modulators of cell-extracellular matrix interactions, proteins, hormones, growth factors, matrix metalloproteinases (MMPS), enzymes and enzyme inhibitors, anticoagulants and/or antithrombic agents, DNA, RNA, modified DNA and RNA, NSAIDs, inhibitors of DNA, RNA or protein synthesis,
  • antibiotics antibiotics, anti-arrhythmic agents, anti-viral agents, analgesics, steroidal anti-inflammatories, non-steroidal antiinflammatories, anti-neoplastics, anti-spasmodics, modulators of cell-extracellular matrix interactions, proteins, hormones, growth factors, matrix metalloproteinases (MMPS), enzymes and enzyme inhibitors, anticoagulants and/or antithrom
  • polypeptides oligonucleotides, polynucleotides, nucleoproteins, compounds modulating cell migration, compounds modulating proliferation and growth of tissue, and vasodilating agents.
  • the terms "pharmacological agent”, “active agent”, “drug” and “active agent formulation” thus include, without limitation, atropine, tropicamide, dexamethasone, dexamethasone phosphate, betamethasone, betamethasone phosphate, prednisolone, triamcinolone, triamcinolone acetonide, fluocinolone acetonide, anecortave acetate, budesonide, cyclosporine, FK-506, rapamycin, ruboxistaurin, midostaurin, flurbiprofen, suprofen, ketoprofen, diclofenac, ketorolac, nepafenac, lidocaine, neomycin, polymyxin b, bacitracin, gramicidin, gentamicin, oyxtetracycline, ciprofloxacin, ofloxacin, tobramycin, amikacin, vanco
  • the terms “pharmacological agent”, “active agent”, “drug” and “active agent formulation” can further include, without limitation, the following growth factors: platelet derived growth factor (PDGF), epidermal growth factor (EGF), transforming growth factor alpha (TGF-alpha), transforming growth factor beta (TGF-beta), fibroblast growth factor - 2 (FGF-2), basic fibroblast growth factor (bFGF), vascular epithelial growth factor (VEGF), hepatocyte growth factor (HGF), insulin-like growth factor (IGF), nerve growth factor (NGF), platlet derived growth factor (PDGF), tumor necrosis factor alpha (TNA-alpha), and placental growth factor (PLGF).
  • PDGF platelet derived growth factor
  • EGF epidermal growth factor
  • TGF-alpha transforming growth factor alpha
  • TGF-beta transforming growth factor beta
  • FGF-2 fibroblast growth factor-2
  • basic fibroblast growth factor bFGF
  • VEGF vascular epitheli
  • the terms "pharmacological agent' * , "active agent”, “drug” and “active agent formulation” further mean and include the following Class I - Class V antian-hythmic agents: (Class la) quinidine, procainamide and disopyramide; (Class lb) lidocaine, phenytoin and mexiletine; (Class Ic) flecainide, propafenone and moricizine; (Class II) propranolol, esmolol, timolol, metoprolol and atenolol; (Class III) amiodarone, sotalol, ibutilide and dofetilide; (Class IV) verapamil and diltiazem) and (Class V) adenosine and digoxin.
  • Class la quinidine, procainamide and disopyramide
  • Class lb lidocaine, phenytoin and mexiletine
  • Class Ic flecainide, prop
  • composition further mean and include, without limitation, the following antiobiotics:
  • trimethoprim-sulfamethoxazole and vancomycin are trimethoprim-sulfamethoxazole and vancomycin.
  • pharmacological agent further include, without limitation, the following steroids: andranes (e.g., testosterone), cholestanes, cholic acids, corticosteroids (e.g., dexamethasone), estraenes (e.g., estradiol) and pregnanes (e.g., progesterone).
  • steroids e.g., testosterone
  • cholestanes e.g., cholestanes
  • cholic acids e.g., corticosteroids (e.g., dexamethasone)
  • corticosteroids e.g., dexamethasone
  • estraenes e.g., estradiol
  • pregnanes e.g., progesterone
  • the terns "pharmacological agent”, “active agent”, “drug” and “active agent formulation” can further include one or more classes of narcotic analgesics, including, without limitation, morphine, codeine, heroin, hydromorphone, levorphanol, meperidine, methadone, oxycodone, propoxyphene, fentanyl, methadone, naloxone, buprenorphine, butorphanol, nalbuphine and pentazocine.
  • narcotic analgesics including, without limitation, morphine, codeine, heroin, hydromorphone, levorphanol, meperidine, methadone, oxycodone, propoxyphene, fentanyl, methadone, naloxone, buprenorphine, butorphanol, nalbuphine and pentazocine.
  • the terms "pharmacological agent”, “active agent”, “drug” and “active agent formulation” can further include one or more classes of topical or local anesthetics, including, without limitation, esters, such as benzocaine, chloroprocaine, cocaine, cyclomethycaine, dimethocaine/larocaine, piperocaine, propoxycaine, procaine/novacaine, proparacaine, and tetracaine/amethocaine.
  • esters such as benzocaine, chloroprocaine, cocaine, cyclomethycaine, dimethocaine/larocaine, piperocaine, propoxycaine, procaine/novacaine, proparacaine, and tetracaine/amethocaine.
  • Local anesthetics can also include, without limitation, amides, such as articaine, bupivacaine, cinchocaine/dibucaine, etidocaine, levobupivacame, lidocaine/lignocaine, mepivacaine, prilocaine, ropivacaine, and trimecaine. Local anesthetics can further include combinations of the above from either amides or esters.
  • cytotoxic anti-neoplastic agents or chemotherapy agents including, without limitation, alkylating agents, cisplatin, carboplatin, oxaliplatin, mechlorethamine, cyclophosphamide, chlorambucil, and ifosfamide.
  • Chemotherapy agents can also include, without limitation, antimetabolites, such as purine analogues, pyrimidine analogues and antifolates, plant alkaloids, such as vincristine, vinblastine, vinorelbine, vindesine, podophyllotoxin, etoposide and teniposide, taxanes, such as paclitaxel and docetaxel, topoisomerase inhibitors, such as irinotecan, topotecan, amsacrine, etoposide, etoposide phosphate and teniposide, cytotoxic antibiotics, such as actinomyocin, bleomycin, plicamycin, mytomycin and anthracyclines, such as doxorubicin, daunorubicin, valrubicin, idarubicin, epirubicin, and antibody treatments, such as abciximab, adamlimumab, alamtuzumab, basilix
  • anti-inflammatory and anti-inflammatory agent are also used interchangeably herein, and mean and include a “pharmacological agent” and/or “active agent formulation”, which, when a therapeutically effective amount is administered to a subject, prevents or treats bodily tissue inflammation i.e. the protective tissue response to injury or destruction of tissues, which serves to destroy, dilute, or wall off both the injurious agent and the injured tissues.
  • Anti-inflammatory agents thus include, without limitation, alclofenac, alclometasone dipropionate, algestone acetonide, alpha amylase, amcinafal, amcinafide, amfenac sodium, amiprilose hydrochloride, anakinra, anirolac, anitrazafen, apazone, balsalazide disodium, bendazac, benoxaprofen, benzydamine hydrochloride, bromelains, broperamole, budesonide, carprofen, cicloprofen, cintazone, cliprofen, clobetasol propionate, clobetasone butyrate, clopirac, cloticasone propionate, cormethasone acetate, cortodoxone, decanoate, deflazacort, delatestryl, depo-testosterone, desonide,
  • stem cells are also used interchangeably herein, and mean and include an organism that has the potential to induce modulating proliferation, and/or growth and/or regeneration of tissue.
  • Stem cells can thus include, without limitation, human embryonic stem cells, fetal cardiomyocytes, myofibroblasts, mesenchymal stem cells, autotransplated expanded cardiomyocytes, adipocytes, totipotent cells, pluripotent cells, blood stem cells, myoblasts, adult stem cells, bone marrow cells, mesenchymal cells, embryonic stem cells, parenchymal cells, epithelial cells, endothelial cells, mesothelial cells, fibroblasts, osteoblasts, chondrocytes, exogenous cells, endogenous cells, stem cells, hematopoietic stem cells, bone-marrow derived progenitor cells, myocardial cells, skeletal cells, fetal cells, undifferentiated cells, multi-potent progenitor cells,
  • the terms “pharmacological agent”, “active agent”, “drug” and “active agent formulation” can further include the following active agents (referred to interchangeably herein as a “protein”, “peptide” and “polypeptide”): collagen (types I-V), proteoglycans, glycosaminoglycans (GAGs), glycoproteins, growth factors, cytokines, cell-surface associated proteins, cell adhesion molecules (CAM), angiogenic growth factors, endothelial ligands, matrikines, cadherins, immuoglobins, fibril collagens, non-fibrallar collagens, basement membrane collagens, multiplexins, small-leucine rich proteoglycans, decorins, biglycans, fibromodulins, keratocans, lumicans, epiphycans, heparin sulfate proteoglycans, perlecans, agrins, testicans, synde
  • active agents referred to interchange
  • active agent formulation means and include an active agent optionally in combination with one or more pharmaceutically acceptable carriers and/or additional inert ingredients.
  • the formulations can be either in solution or in suspension in the earner.
  • composition means and includes a composition comprising a "pharmacological agent” and/or a “pharmacological agent formulation” and/or any additional agent or component identified herein.
  • terapéuticaally effective means that the amount of the "pharmacological composition” and/or “pharmacological agent” and/or “active agent formulation” administered is of sufficient quantity to ameliorate one or more causes, symptoms, or sequelae of a disease or disorder. Such amelioration only requires a reduction or alteration, not necessarily elimination, of the cause, symptom, or sequelae of a disease or disorder.
  • delivery and “administration” are used interchangeably herein, and mean and include providing a “pharmacological composition” or “pharmacological agent” or “active agent formulation” to biological tissue.
  • patient and “subject” are used interchangeably herein, and mean and include warm blooded mammals, humans and primates; avians; domestic household or farm animals, such as cats, dogs, sheep, goats, cattle, horses and pigs; laboratory animals, such as mice, rats and guinea pigs; fish; reptiles; zoo and wild animals; and the like.
  • the two-piece prosthetic valves of the invention can be readily designed and configured and, hence, employed to replace native valves in the body including, without limitation, diseased or defective aortic, pulmonary, mitral, tricuspid and/or peripheral venous valves.
  • the two-piece prosthetic valves include first and second members, a first end of the first member being sized and configured to receive a second end of the second member therein, the second end of the second member being secured to the first member at at least one commissure connection point to form at least one leaflet therein.
  • the second end of the second member is secured to the first member at two commissure connection points to form two leaflets therein.
  • the second end of the second member is secured to the first member at three commissure connection points to form three leaflets therein.
  • the two-piece prosthetic valves also include an anchoring mechanism to position the valves proximate cardiovascular tissue, and maintain contact therewith for a pre-determined anchor support time period.
  • an anchoring mechanism to position the valves proximate cardiovascular tissue, and maintain contact therewith for a pre-determined anchor support time period.
  • Suitable anchoring mechanisms are disclosed in Applicant's Co-pending Application No. 13/782,024, filed March 1 , 2013.
  • the two-piece valve structure can be readily sized and configured to accommodate placement in various cardiovascular vessels, including aortic, pulmonary, mitral, tricuspid and/or peripheral venous vessels.
  • the two-piece prosthetic valves of the invention can also be deployed in various cardiovascular vessels by traditional or minimally invasive means.
  • the first and second valve members and, hence, two- piece valves formed therefrom can comprise various biocompatible materials, including, without limitation, Dacron and mammalian tissue, e.g., bovine tissue.
  • the first and second valve members comprise an extracellular matrix (ECM) material (two-piece valves formed therefrom hereinafter referred to as "two-piece tissue valves").
  • ECM extracellular matrix
  • the ECM material can be derived from various mammalian tissue sources and methods for preparing same, such as disclosed in U.S. Pat. Nos. 7,550,004, 7,244,444, 6,379,710, 6,358,284, 6,206,931 , 5,733,337 and 4,902,508 and U.S. Application No. 12/707,427; which are incorporated by reference herein in their entirety.
  • the mammalian tissue sources include, without limitation, small intestine submucosa (SIS), urinary bladder submucosa (UBS), stomach submucosa (SS), central nervous system tissue, epithelium of mesodermal origin, i.e.
  • the ECM material can also comprise collagen from mammalian sources.
  • UBS urinary bladder submucosa
  • SIS small intestine submucosa
  • SS stomach submucosa
  • the ECM material can also be derived from basement membrane of mammalian tissue/organs, including, without limitation, urinary basement membrane (UBM), liver basement membrane (LBM), and amnion, chorion, allograft pericardium, allograft acellular dermis, amniotic membrane, Wharton's jelly, and combinations thereof.
  • UBM urinary basement membrane
  • LBM liver basement membrane
  • amnion amnion
  • chorion allograft pericardium
  • allograft acellular dermis amniotic membrane
  • Wharton's jelly and combinations thereof.
  • Additional sources of mammalian basement membrane include, without limitation, spleen, lymph nodes, salivary glands, prostate, pancreas and other secreting glands.
  • the ECM material can also be derived from other sources, including, without limitation, collagen from plant sources and synthesized extracellular matrices, i.e. cell cultures.
  • ECM material can comprise, in whole or in part, just the basement membrane (or transitional epithelial layer) with the subadjacent tunica intestinal, the tunica submucosa, tunica muscularis, and tunica serosa.
  • the extracellular matrix component of the ECM material can thus contain any or all of these layers or only the basement membrane portion, excluding the submucosa.
  • the first and/or second valve members and, hence, two-piece tissue valves formed therefrom include at least one pharmacological agent or composition, i.e. an agent that is capable of producing a desired biological effect in vivo, such as stimulation or suppression of cell division, stimulation or suppression of apoptosis, stimulation or suppression of an immune response, anti-bacterial activity, etc.
  • pharmacological agent or composition i.e. an agent that is capable of producing a desired biological effect in vivo, such as stimulation or suppression of cell division, stimulation or suppression of apoptosis, stimulation or suppression of an immune response, anti-bacterial activity, etc.
  • Suitable pharmacological agents and compositions include any of the
  • agents including, without limitation, antibiotics, anti-viral agents, analgesics, steroidal anti-inflammatories, non-steroidal anti-inflammatories, anti-neoplastics, antispasmodics, modulators of cell-extracellular matrix interactions, proteins, hormones, enzymes and enzyme inhibitors, anticoagulants and/or antithrombic agents, DNA, RNA, modified DNA and RNA, NSAIDs, inhibitors of DNA, RNA or protein synthesis, polypeptides, oligonucleotides, polynucleotides, nucleoproteins, compounds modulating cell migration, compounds modulating proliferation and growth of tissue, and vasodilating agents.
  • the pharmacological agent comprises an anti-inflammatory agent.
  • suitable anti-inflammatory agents include, without limitation, alclofenac, alclometasone dipropionate, algestone acetonide, alpha amylase, amcinafal, amcinafide, amfenac sodium, amiprilose hydrochloride, anakinra, anirolac, anitrazafen, apazone, balsalazide disodium, bendazac, benoxaprofen, benzydamine hydrochloride, bromelains, broperamole, budesonide, carprofen, cicloprofen, cintazone, cliprofen, clobetasol propionate, clobetasone butyrate, clopirac, cloticasone propionate, cormethasone acetate, cortodoxone, decanoate, deflazacort, delatestryl, dep
  • halobetasol propionate halopredone acetate, ibufenac, ibuprofen, ibuprofen aluminum, ibuprofen piconol, ilonidap, indomethacin, indomethacin sodium, indoprofen, indoxole, intrazole, isoflupredone acetate, isoxepac, isoxicam, ketoprofen, lofemizole hydrochloride, lomoxicam, loteprednol etabonate, meclotenamate sodium, meclofenamic acid, meclorisone dibutyrate, mefenamic acid, mesalamine, meseclazone, mesterolone, methandrostenolone, methenolone, methenolone acetate, methylprednisolone suleptanate, momiflumate,
  • the pharmacological agent comprises a statin, i.e. a HMG-CoA reductase inhibitor.
  • suitable statins include, without limitation, atorvastatin (Lipitor®), cerivastatin, fluvastatin (Lescol®), lovastatin (Mevacor®, Altocor®, Altoprev®), mevastatin, pitavastatin (Livalo ®, Pitava®), pravastatin (Pravachol®, Selektine®, Lipostat®), rosuvastatin (Crestor®), and simvastatin (Zocor®, Lipex®).
  • actives comprising a combination of a statin and another agent, such as ezetimbe/simvastatin (Vytorin®), are also suitable.
  • statins exhibit numerous beneficial properties that provide several beneficial biochemical actions or activities.
  • the properties and beneficial actions are set forth in Applicant's Co-Pending Application Nos. 13/373,569, filed on September 24, 2012 and 13/782,024, filed on March 1 , 2013; which are incorporated by reference herein in their entirety.
  • the two-piece prosthetic valves can include 10 mg or greater of a statin to achieve a higher concentration of the statin within a desired tissue, or 10 ug or less to achieve a lower concentration of the statin within a desired tissue.
  • the two-piece prosthetic valves also include chitosan or a derivative thereof.
  • chitosan also exhibits numerous beneficial properties that provide several beneficial biochemical actions or activities.
  • the two-piece prosthetic valves include a cell.
  • the cell can comprise, without limitation, a stem cell, such as, for example, a human embryonic stem cell, fetal cell, fetal cardiomyocyte, myofibroblast, mesenchymal stem cell, autotransplanted expanded cardiomyocyte, adipocyte, totipotent cell, pluripotent cell, blood stem cell, myoblast, adult stem cell, bone marrow cell, mesenchymal cell, embryonic stem cell, parenchymal cell, epithelial cell, endothelial cell, mesothelial cell, fibroblast, myofibroblast, osteoblast, chondrocyte, exogenous cell, endogenous cell, stem cell, hematopoetic stem cell, pluripotent stem cell, bone marrow-derived progenitor cell, progenitor cell, myocardial cell, skeletal cell, undifferentiated cell, multi-potent pro
  • a stem cell such as, for example, a human embryonic stem cell
  • the two-piece prosthetic valves include a protein.
  • the protein can comprise, without limitation, a growth factor, collagen, proteoglycan, glycosaminoglycan (GAG) chain, glycoprotein, cytokine, cell-surface associated protein, cell adhesion molecule (CAM), angiogenic growth factor, endothelial ligand, matrikine, matrix metalloprotease, cadherin, immunoglobin, fibril collagen, non-fibrillar collagen, basement membrane collagen, multiplexin, small-leucine rich proteoglycan, decorin, biglycan, fibromodulin, keratocan, lumican, epiphycan, heparan sulfate proteoglycan, perlecan, agrin, testican, syndecan, glypican, serglycin, selectin, lectican, aggrecan, versican, nuerocan, brevican,
  • ACE converting enzyme
  • VEGF vascular epithelial growth factor
  • the two-piece prosthetic valves of the invention further include at least one anchoring mechanism.
  • the anchoring mechanisms can comprise various forms and materials.
  • the anchoring mechanisms comprise reinforcing rings or bands that are positioned and secured at desired positions, e.g. proximal and distal ends, on or in a two-piece valve.
  • the reinforcing rings and bands preferably comprise a biocompatible material, such as a biocompatible metal, e.g., Nitinol ® and stainless steel, and various polymeric materials.
  • the reinforcing rings and bands can also comprise various biodegradable materials, such as magnesium and ECM material.
  • anchoring mechanism and “anchor”, as used in connection with some embodiments of anchored two-piece valves of the invention, including anchored two- piece tissue valves, mean a structure that is configured and employed to temporarily position a two-piece valve of the invention proximate host tissue of a vessel. The function of such an anchoring mechanism is thus to temporarily support and position a two-piece valve of the invention proximate host tissue of a cardiovascular vessel, i.e. vessel wall.
  • the anchoring mechanisms position the anchored two-piece "tissue" valves proximate host tissue of a vessel, and maintain contact therewith for a predetermined temporary anchor support period of time within the process of tissue regeneration.
  • the two-piece prosthetic valve 10 includes first 12 and second 16 members.
  • the first and second members 12, 16 preferable comprise substantially tubular members.
  • the first 12 and second 16 members comprise an extracellular matrix (ECM) material.
  • ECM extracellular matrix
  • the ECM material can be derived from various mammalian tissue sources including, without limitation, small intestinal submucosa, stomach submucosa, large intestinal tissue, urinary bladder submucosa, liver basement membrane, pericardium, epicardium, endocardium, myocardium, lung tissue, kidney tissue, pancreatic tissue, prostate tissue, mesothelial tissue, fetal tissue, a placenta, a ureter, veins, arteries, heart valves with or without their attached vessels, tissue surrounding the roots of developing teeth, and tissue surrounding growing bone.
  • the first 12 and/or second 16 members and, hence, ECM based two-piece tissue valves formed therefrom include at least one
  • Suitable pharmacological agents and compositions include, without limitation, antibiotics, anti-viral agents, analgesics, steroidal antiinflammatories, non-steroidal anti-inflammatories, anti-neoplastics, anti-spasmodics, modulators of cell-extracellular matrix interactions, proteins, hormones, enzymes and enzyme inhibitors, anticoagulants and/or antithrombic agents, DNA, RNA, modified DNA and RNA, NSAIDs, inhibitors of DNA, RNA or protein synthesis, polypeptides, oligonucleotides, polynucleotides, nucleoproteins, compounds modulating cell migration, compounds modulating proliferation and growth of tissue, and vasodilating agents.
  • the pharmacological agent comprises a statin, i.e. a HMG-CoA reductase inhibitor.
  • Suitable statins include, without limitation, atorvastatin (Lipitor®), cerivastatin, fluvastatin (Lescol®), lovastatin (Mevacor®, Altocor®, Altoprev®), mevastatin, pravastatin (Livalo ®, Pitava®), pravastatin (Pravachol®,
  • the pharmacological agent comprises an anti-inflammatory agent.
  • a first end 14 of the first member 12 is sized and configured to receive a second end 18 of the second member 16 therein.
  • the outer diameter of the second member 16 is slightly smaller than the inner diameter of the first member 12.
  • the first 12 and second 16 members can comprise various desired lengths, whereby additional member material can be provided at the second end 15 of the first member 12 and/or first end 17 of the second member 16 to allow a surgeon to control the placement of a two-piece valve on a target vessel, e.g., aorta.
  • the length of the second member end 18 that is disposed within the first member 12, i.e. C determines the height of the commissures or leaflets (or cusps) relative to the annulus.
  • FIG. 2 after the second end 18 of the second member 16 is disposed in the first end 14 of the first member 12, the second member end 18 is secured, i.e. sutured, to the first member 12 at at least one commissure connection point (denoted “20a” in Fig. 5) to form at least one leaflet therein that is configured to selectively prevent undesired regurgitation of blood through the valve structure (denoted "30a").
  • the second member end 18 is secured to the first member 12 at two commissure connection points (denoted “20b” and “20c” in Fig. 6) to form two leaflets therein (denoted “30b” and “30c”).
  • the second member end 18 is secured to the first member 12 at three, preferably, equally spaced positions (denoted “20d”, “20e” and “20f ' in Fig. 4) to commissure connection points to form three leaflets therein (denoted “30d”, “30e” and “30f ').
  • the commissure connection points 20a - 20f can be achieved (or provided) by spot sutures at the connection points.
  • One or more of the commissure connection points 20a - 2 Of, or one or more additional commissure connection points can also be achieved via one or more longitudinal sutures (denoted "22") along the length of the second member end 18 that is disposed within the first member 12.
  • the first member end 14 is also preferably sutured 24 to the second member 16 proximate the second end 18 thereof to provide a sealed connection of the first and second members 12, 16.
  • valve when a two-piece valve of the invention is deployed in a cardiovascular vessel, the valve allows normal blood flow therethrough in the direction denoted by Arrow "BFi" and selectively restricts regurgitation of blood in the direction denoted by Arrow BF?, i.e. the leaflets formed by suturing the second member end 18 to the first member 12 expand and restrict fluid flow therethrough (see Fig. 4).
  • the two-piece valve comprises an ECM based two-piece tissue valve
  • the ECM based two-piece tissue valve will also induce host tissue proliferation, bioremodeling, including neovascularization, e.g., vasculogenesis, angiogenesis, and intussusception, and regeneration of tissue structures with site-specific structural and functional properties.
  • the leaflets 30a - 30f can have various shapes and sizes, such as shown in U.S. Pat. No. 8,257,434 and Co-pending Application No. 13/560,573, which are incorporated by reference herein.
  • each leaflet 30a - 30f i.e. valve structure
  • the shape and length of each leaflet 30a - 30f is, of course, dependent upon the commissure connection points of the second member end 18 and the size, i.e. operative diameter, of the first member 12 member and, hence, valve formed therefrom.
  • the edge length of each leaflet 30a - 30f ranges from approximately 10 mm to approximately 70 mm, more preferably from approximately 15 mm to approximately 60 mm, and most preferably from approximately 25 mm to approximately 45 mm.
  • the ratio between the edge length of each leaflet to the diameter of a target annulus can range from approximately 0.5:1 to approximately 3:1, and more preferably from approximately 1 :1 to approximately 2:1.
  • the disclosed ranges also include all ratios falling between the endpoint ratios.
  • the size or operative diameter and length of the two-piece valves of the invention, including valve 10, described above, can also vary to accommodate placement in various adult and pediatric cardiovascular vessels.
  • the two-piece prosthetic valve 10 further includes at least one anchoring mechanism. In some embodiments, the anchoring
  • mechanisms comprise reinforcing rings or bands that are positioned and secured at desired positions, e.g. proximal and distal ends, on or in a two-piece valve.
  • the anchoring mechanisms are designed and
  • a tubular structure having multiple valves can also be provided by the valve forming method of the invention.
  • Such a structure, i.e. prosthetic multi-valve vessel, is particularly applicable for replacement of defective peripheral venous valves.
  • a single prosthetic multi-valve vessel would also facilitate a simplified delivery and, in some instances, a percutaneous delivery.
  • the prosthetic valves have a pre-determined spacing, preferably, a spacing matching the spacing of the natural venous valves.
  • a prosthetic multi-valve vessel having two prosthetic valves can thus be implanted in a peripheral venous vessel possessing chronic venous insufficiency (CVI), i.e. two valves lacking coaptation, to address the CVI.
  • CVI chronic venous insufficiency
  • the two-piece valves of the invention can thus be readily sized and configured to accommodate placement in various cardiovascular vessels, including aortic, pulmonary, mitral, tricuspid and/or peripheral venous vessels.
  • the present invention provides numerous advantages compared to prior art prosthetic valves. Among the advantages are the following:

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Abstract

L'invention concerne une valvule prothétique en deux parties ayant un premier et un second élément, une première extrémité du premier élément étant dimensionnée et conçue pour recevoir en son sein une seconde extrémité du second élément, la seconde extrémité du second élément étant fixée au premier élément au niveau d'au moins un point de liaison de commissure pour former en son sein au moins un feuillet valvulaire.
PCT/US2013/028611 2013-03-01 2013-03-01 Valvule prothétique en deux parties WO2014133543A1 (fr)

Priority Applications (5)

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AU2013379748A AU2013379748A1 (en) 2013-03-01 2013-03-01 Two-piece prosthetic valve
EP13861485.4A EP2809264A4 (fr) 2013-03-01 2013-03-01 Valvule prothétique en deux parties
PCT/US2013/028611 WO2014133543A1 (fr) 2013-03-01 2013-03-01 Valvule prothétique en deux parties
JP2015560150A JP2016512989A (ja) 2013-03-01 2013-03-01 ツーピース人工弁
HK14112553.8A HK1198904A1 (en) 2013-03-01 2014-12-15 Two-piece prosthetic valve

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AU2013379748A1 (en) 2015-09-17
HK1198904A1 (en) 2015-06-19
EP2809264A4 (fr) 2015-09-09
JP2016512989A (ja) 2016-05-12
EP2809264A1 (fr) 2014-12-10

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