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
  • A61L29/00—Materials for catheters, medical tubing, cannulae, or endoscopes or for coating catheters
  • A61L29/14—Materials characterised by their function or physical properties, e.g. lubricating compositions
  • A61L29/16—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
  • A61L29/00—Materials for catheters, medical tubing, cannulae, or endoscopes or for coating catheters
  • A61L29/08—Materials for coatings
  • A61L29/085—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
  • 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
  • A61L2300/416—Anti-neoplastic or anti-proliferative or anti-restenosis or anti-angiogenic agents, e.g. paclitaxel, sirolimus
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
  • A61M25/00—Catheters; Hollow probes
  • A61M25/10—Balloon catheters
  • A61M2025/1043—Balloon catheters with special features or adapted for special applications
  • A61M2025/105—Balloon catheters with special features or adapted for special applications having a balloon suitable for drug delivery, e.g. by using holes for delivery, drug coating or membranes

Definitions

• suitable polyanionic polymers include, without limitation, carboxymethyl cellulose, sodium carboxymethyl cellulose, carboxymethyl cellulose-cysteine, poly(acrylic acid). poly(methacrylic acid), poly(L-aspartic acid), poly(D-aspartic acid), poly(L-aspartic acid) sodium salt, poly(L-glutamic acid), poly(D-glutamic acid), poly(L-glutamic acid) sodium salt, or combinations thereof.
• a method for manufacturing a system for delivering a therapeutic agent to a vessel wall of a subject comprises providing a system comprising an expandable member having a distal end, a proximal end, and a working length therebetween; and disposing a therapeutic formulation to at least a portion of the working length of the expandable member.
• the formulation comprises a therapeutic agent and a polycationic polymer; wherein the polycationic polymer promotes fibrin formation that increases the residence time and transfer of the therapeutic agent into the vessel wall.
• Carboxymethyl cellulose is used in the approved products Nutropin Depot (Genentech) and Bicillin (Wyeth).
• Polyamino acids can have a favorable safety profile but are much more expensive to employ.
• Homopolymers of amino acids that are un-branched are generally regarded as nonimmunogenic.
• Poly(aspartic acid) and poly(glutamic acid) polymers have the requisite polyionic structural properties to be tissue adhesive, and both are commercially available in a range of molecular weights. Additionally, poly(aspartic acid) and poly(glutamic acid) polymers, which can be metabolized, can be used at a molecular weight above the 40K Dalton renal clearance threshold.
• the adhesive agent comprises a polycationic polymer.
• Polycationic polymers promote adhesion of the therapeutic formulation in part via relatively strong electrostatic interactions with the endothelial glycocalyx of the vessel surface, which is negatively charged (see Giantsos KM, et al. Biomaterials 30 (2009) 5885- 5891).
• the adhesive agent can be combined with dopamine to augment its tissue-adhesive properties.
• the dihydroxyphenol or catechol moiety found in dopamine provide adhesion to surfaces by hydrogen bonding and coordination mechanisms. Such moieties are ubiquitous in mussel and marine mollusk adhesive proteins.
• the adhesion additive can promote adhesion of the therapeutic formulation to the vessel wall by the promotion of fibrin and thrombus formation.
• the polycationic polymer can provide such thrombus- and fibrin-promoting effect.
• platelets are negatively charged (see Ong SY, et al.
• Platelets also have a net negative zeta potential, and accordingly are capable of aggregation in response to electrostatic forces.
• Polycationic polymers also encourage fibrin formation, so that the therapeutic formulation can adhere to the vessel wall via fibrin for a prolonged period of time.
• Polyethyeneimine is alcohol soluble rendering formulation with a therapeutic agent, e.g., zotarolimus, straightforward.
• Chitosan is used in a variety of hemostatic agents for medical and military use. Chitosan has strong adhesive effect to tissue, wounds, and blood.
• Poly-N- acetylglucosamine is a polycationic polysaccharide. Poly-N-acetylglucosamine is the main component of the SyvekPatch hemostat approved by the Food and Drug Administration for use in the local management of bleeding wounds, such as vascular site, percutaneous catheters or tubes, and surgical debridement.
• poly-N-acetyl glucosamine can be obtained from a marine microalgae.
• FIGURE 4 illustrates the mechanism of retention of paclitaxel on a vessel wall studied by Paccocath technology.
• Thrombolytic agents which can be defined as agents that help degrade thrombi (clots), can also be used as adjunctive agents, because the action of lysing a clot helps to disperse platelets trapped within the fibrin matrix of a thrombus.
• clots can also be used as adjunctive agents, because the action of lysing a clot helps to disperse platelets trapped within the fibrin matrix of a thrombus.
• thrombolytic agents include, but are not limited to, urokinase or recombinant urokinase, pro- urokinase or recombinant pro-urokinase, tissue plasminogen activator or its recombinant form, and streptokinase.
• the therapeutic formulation of the disclosed subject matter comprises zotarolimus and polyethyeneimine.
• the ratio of zotarolimus:polyethyeneimine is about 1: 1 by weight.
• the therapeutic formulation can further comprise zotarolimus and poly(L-lysine).
• the ratio of zotarolimus:poly(L- lysine) is about 1: 1 by weight.
• Polyionic polymers are highly polar and soluble in water or highly polar solvents, such as dimethysulfoxide (DMSO), Dimethylacetamide (DMAC), and ethanol. Due to their high polarity and hydrogen bonding, polyionic polymers have Tgs above ambient temperature in the dry state. Consequently, a dry coating of polyionic polymers can be brittle and may have poor coating integrity.
• a solution to provide for good coating integrity when dry is to plasticize the therapeutic formulation with an appropriate plasticizer. Suitable plasticizers are low molecular weight, and water soluble species that are essentially non- volatile.
• the therapeutic formulation further includes a solvent.
• the solvents include, for the purpose of illustration and without limitation, acetone, 2-butanone, cyclopentanone, cyclohexanone, diethyl ether, dipropyl ether, diisopropyl ether, methyl acetate, ethyl acetate, propyl acetate, isopropyl acetate, butyl acetate, methanol, ethanol, n-propanol, isopropanol, n-butanol, isobutanol, sec-butanol, tertiary-butanol, toluene, xylene, pentane, hexane, cyclohexane, heptane, dimethylformamide (DMF), dimethylacetamide (DMAC), and combinations thereof.
• DMF dimethylformamide
• DMAC dimethylacetamide
• the non-ionic polymers include, for the purpose of illustration and without limitation, PVP, silk-elastin like polymer, poly(vinyl alcohol), PEG, pluronics (PEO-PPO-PEO), poly(vinyl acetate), poly(ethylene oxide) (PEO), PVP-vinyl acetate (copovidone), polysorbate 80 (Tween 80), and polysorbate 20 (Tween 20), hydroxyl alkyl celluloses, and combinations thereof.
• the balloon is formed of a polyurethane material, such as TECOTHANE® (Thermedics).
• TECOTHANE® is a thermoplastic, aromatic, polyether polyurethane synthesized from methylene disocyanate (MDI), polytetramethylene ether glycol (PTMEG) and 1,4 butanediol chain extender.
• MDI methylene disocyanate
• PTMEG polytetramethylene ether glycol
• 1,4 butanediol chain extender 1,4 butanediol chain extender.
• TECOTHANE® grade 1065D is suitable in certain embodiments, and has a Shore durometer of 65D, an elongation at break of about 300%, and a high tensile strength at yield of about 10,000 psi.
• other suitable grades can be used, including TECOTHANE® 1075D, having a Shore D hardness of 75.
• the balloon is formed from a low tensile set polymer such as a silicone-polyurethane copolymer.
• the silicone-polyurethane is an ether urethane and more specifically an aliphatic ether urethane such as PURSIL AL 575A and PURSIL ALIO, (Polymer Technology Group), and ELAST-EON 3-70A, (Elastomedics), which are silicone polyether urethane copolymers, and more specifically, aliphatic ether urethane cosiloxanes.
• the low tensile set polymer is a diene polymer.
• diene polymers can be used such as but not limited to an isoprene such as an AB and ABA poly(styrene-block-isoprene), a neoprene, an AB and ABA poly(styrene-block- butadiene) such as styrene butadiene styrene (SBS) and styrene butadiene rubber (SBR), and 1,4- polybutadiene.
• the diene polymer is an isoprene including isoprene copolymers and isoprene block copolymers such as poly(styrene-block-isoprene).
• the balloon does not necessarily include a stent, e.g., is free of a stent.
• a stent can be mounted onto the coated balloon and can further promote uptake.
• the stent will not detrimentally affect coating integrity or drug delivery.
• the type of stent that can be used includes, but is not limited to, a bare metal stent, a balloon expandable stent, a self expanding stent, a drug eluting stent, a prohealing stent, and a self- expanding vulnerable plaque implant.
• the balloon can be coated independently of the stent or in conjunction with the stent coating process.
• the stent coating can contain the same or different therapeutic agents from the balloon catheter or expandable member. However, the particular coating on the balloon catheter or expandable member can have distinct release kinetics from the therapeutic coating on the stent.

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• Health & Medical Sciences (AREA)
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• Animal Behavior & Ethology (AREA)
• General Health & Medical Sciences (AREA)
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• Engineering & Computer Science (AREA)
• Chemical & Material Sciences (AREA)
• Biomedical Technology (AREA)
• Medicinal Chemistry (AREA)
• Molecular Biology (AREA)
• Materials For Medical Uses (AREA)
• Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
• Medicinal Preparation (AREA)
• Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

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• 2013
  • 2013-03-15 EP EP13715068.6A patent/EP2968687A1/en not_active Withdrawn
  • 2013-03-15 WO PCT/US2013/032570 patent/WO2014143048A1/en active Application Filing
  • 2013-03-15 JP JP2016500072A patent/JP6147906B2/ja not_active Expired - Fee Related
  • 2013-03-15 CN CN201380074680.5A patent/CN105228664A/zh active Pending
• 2015
  • 2015-10-15 CR CR20150563A patent/CR20150563A/es unknown

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