US20050143678A1 - Confinement of kidney-stone fragments during lithotripsy - Google Patents

Confinement of kidney-stone fragments during lithotripsy Download PDF

Info

Publication number
US20050143678A1
US20050143678A1 US10963410 US96341004A US2005143678A1 US 20050143678 A1 US20050143678 A1 US 20050143678A1 US 10963410 US10963410 US 10963410 US 96341004 A US96341004 A US 96341004A US 2005143678 A1 US2005143678 A1 US 2005143678A1
Authority
US
Grant status
Application
Patent type
Prior art keywords
method
inverse thermosensitive
thermosensitive polymer
lumen
kidney
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Abandoned
Application number
US10963410
Inventor
Alexander Schwarz
W. McDougal
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
General Hospital Corp
Genzyme Corp
Original Assignee
Pluromed 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

Links

Images

Classifications

    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B17/00Surgical instruments, devices or methods, e.g. tourniquets
    • A61B17/12Surgical instruments, devices or methods, e.g. tourniquets for ligaturing or otherwise compressing tubular parts of the body, e.g. blood vessels, umbilical cord
    • A61B17/12022Occluding by internal devices, e.g. balloons or releasable wires
    • A61B17/12027Type of occlusion
    • A61B17/1204Type of occlusion temporary occlusion
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B17/00Surgical instruments, devices or methods, e.g. tourniquets
    • A61B17/12Surgical instruments, devices or methods, e.g. tourniquets for ligaturing or otherwise compressing tubular parts of the body, e.g. blood vessels, umbilical cord
    • A61B17/12022Occluding by internal devices, e.g. balloons or releasable wires
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B17/00Surgical instruments, devices or methods, e.g. tourniquets
    • A61B17/12Surgical instruments, devices or methods, e.g. tourniquets for ligaturing or otherwise compressing tubular parts of the body, e.g. blood vessels, umbilical cord
    • A61B17/12022Occluding by internal devices, e.g. balloons or releasable wires
    • A61B17/12027Type of occlusion
    • A61B17/1204Type of occlusion temporary occlusion
    • A61B17/12045Type of occlusion temporary occlusion double occlusion, e.g. during anastomosis
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B17/00Surgical instruments, devices or methods, e.g. tourniquets
    • A61B17/12Surgical instruments, devices or methods, e.g. tourniquets for ligaturing or otherwise compressing tubular parts of the body, e.g. blood vessels, umbilical cord
    • A61B17/12022Occluding by internal devices, e.g. balloons or releasable wires
    • A61B17/12099Occluding by internal devices, e.g. balloons or releasable wires characterised by the location of the occluder
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B17/00Surgical instruments, devices or methods, e.g. tourniquets
    • A61B17/12Surgical instruments, devices or methods, e.g. tourniquets for ligaturing or otherwise compressing tubular parts of the body, e.g. blood vessels, umbilical cord
    • A61B17/12022Occluding by internal devices, e.g. balloons or releasable wires
    • A61B17/12131Occluding by internal devices, e.g. balloons or releasable wires characterised by the type of occluding device
    • A61B17/12181Occluding by internal devices, e.g. balloons or releasable wires characterised by the type of occluding device formed by fluidized, gelatinous or cellular remodelable materials, e.g. embolic liquids, foams or extracellular matrices
    • A61B17/12186Occluding by internal devices, e.g. balloons or releasable wires characterised by the type of occluding device formed by fluidized, gelatinous or cellular remodelable materials, e.g. embolic liquids, foams or extracellular matrices liquid materials adapted to be injected
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B17/00Surgical instruments, devices or methods, e.g. tourniquets
    • A61B17/22Implements for squeezing-off ulcers or the like on the inside of inner organs of the body; Implements for scraping-out cavities of body organs, e.g. bones; Calculus removers; Calculus smashing apparatus; Apparatus for removing obstructions in blood vessels, not otherwise provided for
    • A61B17/22004Implements for squeezing-off ulcers or the like on the inside of inner organs of the body; Implements for scraping-out cavities of body organs, e.g. bones; Calculus removers; Calculus smashing apparatus; Apparatus for removing obstructions in blood vessels, not otherwise provided for using mechanical vibrations, e.g. ultrasonic shock waves
    • A61B17/22012Implements for squeezing-off ulcers or the like on the inside of inner organs of the body; Implements for scraping-out cavities of body organs, e.g. bones; Calculus removers; Calculus smashing apparatus; Apparatus for removing obstructions in blood vessels, not otherwise provided for using mechanical vibrations, e.g. ultrasonic shock waves in direct contact with, or very close to, the obstruction or concrement
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B17/00Surgical instruments, devices or methods, e.g. tourniquets
    • A61B17/22Implements for squeezing-off ulcers or the like on the inside of inner organs of the body; Implements for scraping-out cavities of body organs, e.g. bones; Calculus removers; Calculus smashing apparatus; Apparatus for removing obstructions in blood vessels, not otherwise provided for
    • A61B17/22004Implements for squeezing-off ulcers or the like on the inside of inner organs of the body; Implements for scraping-out cavities of body organs, e.g. bones; Calculus removers; Calculus smashing apparatus; Apparatus for removing obstructions in blood vessels, not otherwise provided for using mechanical vibrations, e.g. ultrasonic shock waves
    • A61B17/22012Implements for squeezing-off ulcers or the like on the inside of inner organs of the body; Implements for scraping-out cavities of body organs, e.g. bones; Calculus removers; Calculus smashing apparatus; Apparatus for removing obstructions in blood vessels, not otherwise provided for using mechanical vibrations, e.g. ultrasonic shock waves in direct contact with, or very close to, the obstruction or concrement
    • A61B17/2202Implements for squeezing-off ulcers or the like on the inside of inner organs of the body; Implements for scraping-out cavities of body organs, e.g. bones; Calculus removers; Calculus smashing apparatus; Apparatus for removing obstructions in blood vessels, not otherwise provided for using mechanical vibrations, e.g. ultrasonic shock waves in direct contact with, or very close to, the obstruction or concrement the ultrasound transducer being inside patient's body at the distal end of the catheter
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B17/00Surgical instruments, devices or methods, e.g. tourniquets
    • A61B17/22Implements for squeezing-off ulcers or the like on the inside of inner organs of the body; Implements for scraping-out cavities of body organs, e.g. bones; Calculus removers; Calculus smashing apparatus; Apparatus for removing obstructions in blood vessels, not otherwise provided for
    • A61B17/22004Implements for squeezing-off ulcers or the like on the inside of inner organs of the body; Implements for scraping-out cavities of body organs, e.g. bones; Calculus removers; Calculus smashing apparatus; Apparatus for removing obstructions in blood vessels, not otherwise provided for using mechanical vibrations, e.g. ultrasonic shock waves
    • A61B17/22012Implements for squeezing-off ulcers or the like on the inside of inner organs of the body; Implements for scraping-out cavities of body organs, e.g. bones; Calculus removers; Calculus smashing apparatus; Apparatus for removing obstructions in blood vessels, not otherwise provided for using mechanical vibrations, e.g. ultrasonic shock waves in direct contact with, or very close to, the obstruction or concrement
    • A61B17/22022Implements for squeezing-off ulcers or the like on the inside of inner organs of the body; Implements for scraping-out cavities of body organs, e.g. bones; Calculus removers; Calculus smashing apparatus; Apparatus for removing obstructions in blood vessels, not otherwise provided for using mechanical vibrations, e.g. ultrasonic shock waves in direct contact with, or very close to, the obstruction or concrement using electric discharge
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B17/00Surgical instruments, devices or methods, e.g. tourniquets
    • A61B17/22Implements for squeezing-off ulcers or the like on the inside of inner organs of the body; Implements for scraping-out cavities of body organs, e.g. bones; Calculus removers; Calculus smashing apparatus; Apparatus for removing obstructions in blood vessels, not otherwise provided for
    • A61B17/225Implements for squeezing-off ulcers or the like on the inside of inner organs of the body; Implements for scraping-out cavities of body organs, e.g. bones; Calculus removers; Calculus smashing apparatus; Apparatus for removing obstructions in blood vessels, not otherwise provided for for extracorporeal shock wave lithotripsy [ESWL], e.g. by using ultrasonic waves
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B18/00Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body
    • A61B18/18Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body by applying electromagnetic radiation, e.g. microwaves
    • A61B18/20Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body by applying electromagnetic radiation, e.g. microwaves using laser
    • A61B18/22Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body by applying electromagnetic radiation, e.g. microwaves using laser the beam being directed along or through a flexible conduit, e.g. an optical fibre; Couplings or hand-pieces therefor
    • A61B18/26Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body by applying electromagnetic radiation, e.g. microwaves using laser the beam being directed along or through a flexible conduit, e.g. an optical fibre; Couplings or hand-pieces therefor for producing a shock wave, e.g. laser lithotripsy
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61HPHYSICAL THERAPY APPARATUS, e.g. DEVICES FOR LOCATING OR STIMULATING REFLEX POINTS IN THE BODY; ARTIFICIAL RESPIRATION; MASSAGE; BATHING DEVICES FOR SPECIAL THERAPEUTIC OR HYGIENIC PURPOSES OR SPECIFIC PARTS OF THE BODY
    • A61H23/00Percussion or vibration massage, e.g. using supersonic vibration; Suction-vibration massage; Massage with moving diaphragms
    • A61H23/008Percussion or vibration massage, e.g. using supersonic vibration; Suction-vibration massage; Massage with moving diaphragms using shock waves
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B17/00Surgical instruments, devices or methods, e.g. tourniquets
    • A61B17/12Surgical instruments, devices or methods, e.g. tourniquets for ligaturing or otherwise compressing tubular parts of the body, e.g. blood vessels, umbilical cord
    • A61B17/12022Occluding by internal devices, e.g. balloons or releasable wires
    • A61B2017/12127Double occlusion, e.g. for creating blood-free anastomosis site
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B17/00Surgical instruments, devices or methods, e.g. tourniquets
    • A61B17/22Implements for squeezing-off ulcers or the like on the inside of inner organs of the body; Implements for scraping-out cavities of body organs, e.g. bones; Calculus removers; Calculus smashing apparatus; Apparatus for removing obstructions in blood vessels, not otherwise provided for
    • A61B17/22004Implements for squeezing-off ulcers or the like on the inside of inner organs of the body; Implements for scraping-out cavities of body organs, e.g. bones; Calculus removers; Calculus smashing apparatus; Apparatus for removing obstructions in blood vessels, not otherwise provided for using mechanical vibrations, e.g. ultrasonic shock waves
    • A61B17/22012Implements for squeezing-off ulcers or the like on the inside of inner organs of the body; Implements for scraping-out cavities of body organs, e.g. bones; Calculus removers; Calculus smashing apparatus; Apparatus for removing obstructions in blood vessels, not otherwise provided for using mechanical vibrations, e.g. ultrasonic shock waves in direct contact with, or very close to, the obstruction or concrement
    • A61B17/2202Implements for squeezing-off ulcers or the like on the inside of inner organs of the body; Implements for scraping-out cavities of body organs, e.g. bones; Calculus removers; Calculus smashing apparatus; Apparatus for removing obstructions in blood vessels, not otherwise provided for using mechanical vibrations, e.g. ultrasonic shock waves in direct contact with, or very close to, the obstruction or concrement the ultrasound transducer being inside patient's body at the distal end of the catheter
    • A61B2017/22021Implements for squeezing-off ulcers or the like on the inside of inner organs of the body; Implements for scraping-out cavities of body organs, e.g. bones; Calculus removers; Calculus smashing apparatus; Apparatus for removing obstructions in blood vessels, not otherwise provided for using mechanical vibrations, e.g. ultrasonic shock waves in direct contact with, or very close to, the obstruction or concrement the ultrasound transducer being inside patient's body at the distal end of the catheter electric leads passing through the catheter
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B17/00Surgical instruments, devices or methods, e.g. tourniquets
    • A61B17/22Implements for squeezing-off ulcers or the like on the inside of inner organs of the body; Implements for scraping-out cavities of body organs, e.g. bones; Calculus removers; Calculus smashing apparatus; Apparatus for removing obstructions in blood vessels, not otherwise provided for
    • A61B17/22004Implements for squeezing-off ulcers or the like on the inside of inner organs of the body; Implements for scraping-out cavities of body organs, e.g. bones; Calculus removers; Calculus smashing apparatus; Apparatus for removing obstructions in blood vessels, not otherwise provided for using mechanical vibrations, e.g. ultrasonic shock waves
    • A61B17/22012Implements for squeezing-off ulcers or the like on the inside of inner organs of the body; Implements for scraping-out cavities of body organs, e.g. bones; Calculus removers; Calculus smashing apparatus; Apparatus for removing obstructions in blood vessels, not otherwise provided for using mechanical vibrations, e.g. ultrasonic shock waves in direct contact with, or very close to, the obstruction or concrement
    • A61B2017/22025Implements for squeezing-off ulcers or the like on the inside of inner organs of the body; Implements for scraping-out cavities of body organs, e.g. bones; Calculus removers; Calculus smashing apparatus; Apparatus for removing obstructions in blood vessels, not otherwise provided for using mechanical vibrations, e.g. ultrasonic shock waves in direct contact with, or very close to, the obstruction or concrement applying a shock wave
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B17/00Surgical instruments, devices or methods, e.g. tourniquets
    • A61B17/22Implements for squeezing-off ulcers or the like on the inside of inner organs of the body; Implements for scraping-out cavities of body organs, e.g. bones; Calculus removers; Calculus smashing apparatus; Apparatus for removing obstructions in blood vessels, not otherwise provided for
    • A61B2017/22051Implements for squeezing-off ulcers or the like on the inside of inner organs of the body; Implements for scraping-out cavities of body organs, e.g. bones; Calculus removers; Calculus smashing apparatus; Apparatus for removing obstructions in blood vessels, not otherwise provided for with an inflatable part, e.g. balloon, for positioning, blocking, or immobilisation
    • A61B2017/22054Implements for squeezing-off ulcers or the like on the inside of inner organs of the body; Implements for scraping-out cavities of body organs, e.g. bones; Calculus removers; Calculus smashing apparatus; Apparatus for removing obstructions in blood vessels, not otherwise provided for with an inflatable part, e.g. balloon, for positioning, blocking, or immobilisation with two balloons
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B17/00Surgical instruments, devices or methods, e.g. tourniquets
    • A61B17/22Implements for squeezing-off ulcers or the like on the inside of inner organs of the body; Implements for scraping-out cavities of body organs, e.g. bones; Calculus removers; Calculus smashing apparatus; Apparatus for removing obstructions in blood vessels, not otherwise provided for
    • A61B2017/22051Implements for squeezing-off ulcers or the like on the inside of inner organs of the body; Implements for scraping-out cavities of body organs, e.g. bones; Calculus removers; Calculus smashing apparatus; Apparatus for removing obstructions in blood vessels, not otherwise provided for with an inflatable part, e.g. balloon, for positioning, blocking, or immobilisation
    • A61B2017/22065Functions of balloons
    • A61B2017/22067Blocking; Occlusion
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B17/00Surgical instruments, devices or methods, e.g. tourniquets
    • A61B17/22Implements for squeezing-off ulcers or the like on the inside of inner organs of the body; Implements for scraping-out cavities of body organs, e.g. bones; Calculus removers; Calculus smashing apparatus; Apparatus for removing obstructions in blood vessels, not otherwise provided for
    • A61B2017/22082Implements for squeezing-off ulcers or the like on the inside of inner organs of the body; Implements for scraping-out cavities of body organs, e.g. bones; Calculus removers; Calculus smashing apparatus; Apparatus for removing obstructions in blood vessels, not otherwise provided for after introduction of a substance
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61FFILTERS 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
    • A61F2/00Filters 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
    • A61F2/01Filters implantable into blood vessels
    • A61F2/013Distal protection devices, i.e. devices placed distally in combination with another endovascular procedure, e.g. angioplasty or stending

Abstract

The present invention improves significantly the success rate of lithotripsy and reduces the risk of tissue damage, by injecting temporary plugs in front and behind a concretion (for extracorporeal lithotripsy) or behind a concretion (for intracorporeal lithotripsy). One aspect of the present invention relates to injecting an inverse thermosensitive polymer solution into a lumen, thereby preventing the migration of a concretion, or its fragments, upon extracorporeal or intracorporeal lithotripsy.

Description

    RELATED APPLICATIONS
  • This application claims the benefit of priority to U.S. Provisional Patent Application Ser. No. 60/510,505, filed Oct. 14, 2003; the specification of which is hereby incorporated in its entirety by reference.
  • BACKGROUND
  • The prevalence of urolithiasis, or kidney stone disease, is increasing with an aging population. A recent German epidemiology study showed an increase in the prevalence of kidney stones in the general German population from about 0.5% in 1971 to about 1.5% in 2000. (Hesse A. et al. European Urology 2003, 44, 709-713). Urolithiasis is also a significant health problem in the United States. It is estimated that between 5-10% of the general population will develop a urinary concretion during their lifetime. (Pak, C. T. Diseases of the Kidney, 5th Edition; Boston; Little, Brown & Co.; 1993; pp. 729-743). The peak onset of urolithiasis is typically between 20 and 30 years of age, and males are effected more often then females.
  • Since being introduced in the 1980s, minimally invasive procedures such as lithotripsy, as well as ureteroscopy, have become the preferred methods for treatment in a majority of cases of concretions in the ureter, and have a potential for application to concretions that develop in other parts of the body such as the pancreas and the gallbladder. Lithotripsy is a medical procedure that uses energy in various forms such as acoustic shock waves, pneumatic pulsation, electrical hydraulic shock waves, or laser beams to break up biological concretions such as urinary calculi (e.g., kidney stones). The force of the energy, when applied either extracorporeally or intracorporeally, usually in focused and continuous or successive bursts, comminutes a kidney stone into smaller fragments that may be extracted from the body or allowed to pass through urination. Applications to other concretions formed in the body, such as pancreatic, salivary and biliary stones as well as the vascular system, are currently underway in several research laboratories across the United States and Europe.
  • As mentioned above, the introduction of extracorporeal shockwave lithotripsy (ESWL) in 1980 changed the management of renal and ureteral calculous disease from a surgical to a noninvasive procedure. ESWL is a procedure in which renal and ureteral calculi are broken up into smaller fragments by shock waves. These small fragments then can pass spontaneously. All shock wave generators are based on the geometrical principle of an ellipse. Shock waves are created at the first focal point of an ellipsoid (‘F1’), within the half ellipse, and are directed towards the second focal point (‘F2’), within the patient. The focal zone is the area at F2 where the shock wave is concentrated. The focal zone of the original Dornier HM3 exceeded 2 cm; most new electromagnetic generators have focal zones that average only 6 mm. The energy in these shock waves breaks a larger stone into smaller stones. This noninvasive approach allows patients to be rendered stone-free without surgical intervention or endoscopic procedures.
  • However there are several complications which can result from standard ESWL. Clinical experience demonstrates that a typical fragmentation rate of about 85%, and a stone-free rate of about 65-70%, is achievable with ESWL. A major problem with the procedure is that when kidney stones are fragmented the energy is sufficient to widely distribute them throughout the ureter and kidney. Further, fragments might become undetectable (e.g., too small to be imaged by fluoroscopy) but still too big to be easily passed. In addition, after the stones fragment, the shock wave treatment still focuses on the focal point F2, and the redistribution of the stones could move them outside the range of the treatment. Therefore, during the procedure it would be highly beneficial to confine the kidney stone and the resulting fragments into a narrow space within the focal point of F2. An improvement in this approach, which is described herein, would be to place a plug behind and in front of the stone, thereby confining the stone to a particular space. After the procedure the plugs could be removed and the smaller stones allowed to pass.
  • A different approach to the treatment of kidney stones is intracorporeal lithotripsy. A common approach employs laser energy at 2100 nm, generated by a holmium:YAG laser. A coumarin dye laser may also be used. The laser produces a vaporization bubble at the tip of the fiber optic and the energy is transferred to the stone and leads to fragmentation. However, proximal ureteral stone migration during laser lithotripsy accounts for a high percentage of ureteroscopic failures. In addition there is an electro-hydraulic technique, which utilizes electric discharge, ignited between two electrodes disposed within the probe and producing shock wave, expanding towards the concretion through liquid phase, which surrounds the concretion. Various mechanical anti-migration backstops have been developed and involve the placement of these devices behind the kidney stone, with respect to the laser or shock wave, and subsequent extraction of the smaller stones post fragmentation. A simpler approach, described herein, would be to introduce a temporary plug behind the stone, preventing the stone and its fragments from migrating further up the urethra or kidney. This approach would require a plug that was easily removable after the fragmentation.
  • It is an object of the invention to facilitate lithotripsy. The invention generally includes the use of a material (inverse thermosensitive polymers) that exists in liquid form and is transformed into a gel inside the body of a patient. The inverse thermosensitive polymers of the invention generally includes the use of a material that exists in liquid form at temperatures below about body temperature and as a gel at temperatures about at and above body temperature. The temperature at which the transition from liquid to gel occurs is referred to as the inverse thermosensitive polymer, and it can be a small temperature range as opposed to a specific temperature.
  • SUMMARY OF THE INVENTION
  • One aspect of the present invention relates to a method of lithotripsy comprising the steps of: injecting a first composition, comprising an inverse thermosensitive polymer, into a lumen of a mammal, at a first distance from a concretion, wherein said first composition does not contact said concretion; optionally injecting a second composition, comprising an inverse thermosensitive polymer, into said lumen, at a second distance from said concretion, wherein said second composition is placed on the approximately opposite side of said concretion relative to said first composition, wherein said second composition does not contact said concretion; and directing energy to said concretion causing the fragmentation of said concretion into a plurality of fragments.
  • In certain embodiments, the present invention relates to the aforementioned method, wherein said inverse thermosensitive polymer is a block copolymer, random copolymer, graft polymer, or branched copolymer.
  • In certain embodiments, the present invention relates to the aforementioned method, wherein said inverse thermosensitive polymer is a block polymer or a branched copolymer.
  • In certain embodiments, the present invention relates to the aforementioned method, wherein said inverse thermosensitive polymer is an optionally purified poloxamer or poloxamine.
  • In certain embodiments, the present invention relates to the aforementioned method, wherein said inverse thermosensitive polymer is optionally purified and selected from the group consisting of poloxamine 1107, poloxamine 1307, poloxamer 338 and poloxamer 407.
  • In certain embodiments, the present invention relates to the aforementioned method, wherein said inverse thermosensitive polymer is an optionally purified poloxamer 407.
  • In certain embodiments, the present invention relates to the aforementioned method, wherein said inverse thermosensitive polymer solution has a transition temperature of between about 10° C. and 40° C.
  • In certain embodiments, the present invention relates to the aforementioned method, wherein said inverse thermosensitive polymer solution has a transition temperature of between about 15° C. and 30° C.
  • In certain embodiments, the present invention relates to the aforementioned method, wherein said inverse thermosensitive polymer solution has a transition temperature of about 25° C.
  • In certain embodiments, the present invention relates to the aforementioned method, wherein said first distance is between about 1 cm and about 5 cm.
  • In certain embodiments, the present invention relates to the aforementioned method, wherein said first distance is between about 2 cm and about 4 cm.
  • In certain embodiments, the present invention relates to the aforementioned method, wherein said first distance is about 3 cm.
  • In certain embodiments, the present invention relates to the aforementioned method, wherein said second distance is between about 1 cm and about 5 cm.
  • In certain embodiments, the present invention relates to the aforementioned method, wherein said second distance is between about 2 cm and about 4 cm.
  • In certain embodiments, the present invention relates to the aforementioned method, wherein said second distance is about 3 cm.
  • In certain embodiments, the present invention relates to the aforementioned method, wherein said composition is injected into said lumen through a percutaneous access device.
  • In certain embodiments, the present invention relates to the aforementioned method, wherein said composition is injected into said lumen through a catheter or a syringe.
  • In certain embodiments, the present invention relates to the aforementioned method, wherein the catheter is a dual lumen catheter or a triple lumen catheter.
  • In certain embodiments, the present invention relates to the aforementioned method, wherein said energy is an acoustic shock wave, a pneumatic pulsation, an electrical hydraulic shock wave, or a laser beam.
  • In certain embodiments, the present invention relates to the aforementioned method, wherein said lumen is, or is part of, a kidney, a gall bladder, a ureter, a urinary bladder, a pancreas, a salivary gland, a small intestine or a large intestine.
  • In certain embodiments, the present invention relates to the aforementioned method, wherein said lumen is, or is part of, the ureter or kidney.
  • In certain embodiments, the present invention relates to the aforementioned method, wherein said concretion is a kidney stone, pancreatic stone, salivary stone, or biliary stone.
  • In certain embodiments, the present invention relates to the aforementioned method, wherein said concretion is a kidney stone.
  • In certain embodiments, the present invention relates to the aforementioned method, wherein said mammal is a human.
  • In certain embodiments, the present invention relates to the aforementioned method, wherein said composition comprises about 5% to about 30% of said inverse thermosensitive polymer.
  • In certain embodiments, the present invention relates to the aforementioned method, wherein said composition comprises about 10% to about 25% said inverse thermosensitive polymer.
  • In certain embodiments, the present invention relates to the aforementioned method, wherein said composition comprising an inverse thermosensitive polymer further comprises a contrast-enhancing agent.
  • In certain embodiments, the present invention relates to the aforementioned method, wherein said contrast-enhancing agent is selected from the group consisting of radiopaque materials, paramagnetic materials, heavy atoms, transition metals, lanthanides, actinides, dyes, and radionuclide-containing materials.
  • In certain embodiments, the present invention relates to the aforementioned method, wherein the inverse thermosensitive polymer has a polydispersity index from about 1.5 to 1.0.
  • In certain embodiments, the present invention relates to the aforementioned method, wherein the inverse thermosensitive polymer has a polydispersity index from about 1.2 to 1.0.
  • In certain embodiments, the present invention relates to the aforementioned method, wherein the inverse thermosensitive polymer has a polydispersity index from about 1.1 to 1.0.
  • In certain embodiments, the present invention relates to the aforementioned method, wherein said inverse thermosensitive polymer is an optionally purified poloxamer or poloxamine; and said inverse thermosensitive polymer solution has a transition temperature of between about 10° C. and 40° C.
  • In certain embodiments, the present invention relates to the aforementioned method, wherein said inverse thermosensitive polymer is an optionally purified poloxamer or poloxamine; and said inverse thermosensitive polymer solution has a transition temperature of between about 15° C. and 30° C.
  • In certain embodiments, the present invention relates to the aforementioned method, wherein said inverse thermosensitive polymer is an optionally purified poloxamer or poloxamine; and said inverse thermosensitive polymer solution has a transition temperature of about 25° C.
  • In certain embodiments, the present invention relates to the aforementioned method, wherein said energy is an acoustic shock wave, a pneumatic pulsation, an electrical hydraulic shock wave, or a laser beam; and said lumen is, or is part of, a kidney, a gall bladder, a ureter, a urinary bladder, a pancreas, a salivary gland, a small intestine or a large intestine.
  • In certain embodiments, the present invention relates to the aforementioned method, wherein said inverse thermosensitive polymer is optionally purified and selected from the group consisting of poloxamine 1107, poloxamine 1307, poloxamer 338 and poloxamer 407; and said lumen is, or is part of, a kidney, a gall bladder, a ureter, a urinary bladder, a pancreas, a salivary gland, a small intestine or a large intestine.
  • In certain embodiments, the present invention relates to the aforementioned method, wherein said inverse thermosensitive polymer is optionally purified poloxamer 407; and said lumen is, or is part of, the ureter or kidney.
  • In certain embodiments, the present invention relates to the aforementioned method, wherein said inverse thermosensitive polymer is optionally purified and selected from the group consisting of poloxamine 1107, poloxamine 1307, poloxamer 338 and poloxamer 407; wherein said energy is an acoustic shock wave, a pneumatic pulsation, an electrical hydraulic shock wave, or a laser beam; and said lumen is, or is part of, a kidney, a gall bladder, a ureter, a urinary bladder, a pancreas, a salivary gland, a small intestine or a large intestine.
  • In certain embodiments, the present invention relates to the aforementioned method, wherein said inverse thermosensitive polymer is an optionally purified poloxamer or poloxamine; said inverse thermosensitive polymer solution has a transition temperature of between about 10° C. and 40° C.; said energy is an acoustic shock wave, a pneumatic pulsation, an electrical hydraulic shock wave, or a laser beam; and said lumen is, or is part of, a kidney, a gall bladder, a ureter, a urinary bladder, a pancreas, a salivary gland, a small intestine or a large intestine.
  • In certain embodiments, the present invention relates to the aforementioned method, wherein said inverse thermosensitive polymer is an optionally purified poloxamer or poloxamine; wherein said inverse thermosensitive polymer solution has a transition temperature of between about 15° C. and 30° C.; said energy is an acoustic shock wave, a pneumatic pulsation, an electrical hydraulic shock wave, or a laser beam; and said lumen is, or is part of, a kidney, a gall bladder, a ureter, a urinary bladder, a pancreas, a salivary gland, a small intestine or a large intestine.
  • In certain embodiments, the present invention relates to the aforementioned method, wherein said inverse thermosensitive polymer is an optionally purified poloxamer or poloxamine; said inverse thermosensitive polymer solution has a transition temperature of about 25° C.; said energy is an acoustic shock wave, a pneumatic pulsation, an electrical hydraulic shock wave, or a laser beam; and said lumen is, or is part of, a kidney, a gall bladder, a ureter, a urinary bladder, a pancreas, a salivary gland, a small intestine or a large intestine.
  • In certain embodiments, the present invention relates to the aforementioned method, wherein said inverse thermosensitive polymer is an optionally purified poloxamer or poloxamine; said inverse thermosensitive polymer solution has a transition temperature of between about 10° C. and 40° C.; said energy is an electrical hydraulic shock wave; and said lumen is, or is part of, the ureter or kidney.
  • BRIEF DESCRIPTION OF FIGURES
  • FIG. 1 depicts the deployment of a catheter into a lumen containing a concretion.
  • FIG. 2 depicts the deployment of a thermosensitive polymer composition and the formation of a plug behind the concretion.
  • FIG. 3 depicts the position of the gel (plug) and concretion before lithotripsy.
  • FIG. 4 depicts the deployment of a lithotripsy probe for intracorporeal lithotripsy.
  • FIG. 5 depicts the result of fragmentation of the concretion, wherein the concretion fragments are prevented from widely distributing through out the kidney.
  • FIG. 6 depicts the dissolution of the gel (plug) via the injection of a saline solution into the gel via a catheter.
  • FIG. 7 depicts the ureter after the dissolution of the gel (plug), with small concretion fragments which can easily be passed.
  • DETAILED DESCRIPTION OF THE INVENTION
  • Overview
  • The present invention improves significantly the success rate of lithotripsy and reduces the risk of tissue damage, by injecting temporary plugs in front and behind a concretion (external shock wave lithotripsy) or behind a concretion (intracorporeal lithotripsy). The present invention mitigates the risk of damage to surrounding body tissue when performing lithotripsy to removing organic material (e.g., biological concretions such as urinary, biliary, and pancreatic stones) which may obstruct or otherwise be present within the body's anatomical lumens. One aspect of the present invention relates to injecting an inverse thermosensitive polymer solution into a lumen, thereby preventing the migration of a concretion, or its fragments, during extracorporeal or intracorporeal lithotripsy. In one embodiment, the invention prevents the upward migration of concretion fragments generated during a fragmentation procedure. The invention also enables repeated or continuous application of energy to a concretion, and its resulting fragments, or other biological and non-biological/foreign material, while minimizing trauma to the surrounding tissue. The present invention improves significantly the success rate of lithotripsy, reduces the risk of tissue damage, and decreases the procedure time.
  • Definitions
  • For convenience, certain terms employed in the specification, exemplification, and appended claims are collected here.
  • The articles “a” and “an” are used herein to refer to one or to more than one (i.e., to at least one) of the grammatical object of the article. By way of example, “an element” means one element or more than one element.
  • The terms “reversibly gelling” and “inverse thermosensitive” refer to the property of a polymer wherein gelation takes place upon an increase in temperature, rather than a decrease in temperature.
  • The term “transition temperature” refers to the temperature or temperature range at which gelation of an inverse thermosensitive polymer occurs.
  • The term “contrast-enhancing” refers to materials capable of being monitored during injection into a mammalian subject by methods for monitoring and detecting such materials, for example by radiography or fluoroscopy. An example of a contrast-enhancing agent is a radiopaque material. Contrast-enhancing agents including radiopaque materials may be either water soluble or water insoluble. Examples of water soluble radiopaque materials include metrizamide, iopamidol, iothalamate sodium, iodomide sodium, and meglumine. Examples of water insoluble radiopaque materials include metals and metal oxides such as gold, titanium, silver, stainless steel, oxides thereof, aluminum oxide, zirconium oxide, etc.
  • As used herein, the term “polymer” means a molecule, formed by the chemical union of two or more oligomer units. The chemical units are normally linked together by covalent linkages. The two or more combining units in a polymer can be all the same, in which case the polymer is referred to as a homopolymer. They can be also be different and, thus, the polymer will be a combination of the different units. These polymers are referred to as copolymers.
  • The term “biocompatible”, as used herein, refers to having the property of being biologically compatible by not producing a toxic, injurious, or immunological response in living tissue.
  • The term “poloxamer” denotes a symmetrical block copolymer, consisting of a core of PPG polyoxyethylated to both its terminal hydroxyl groups, i.e. conforming to the interchangeable generic formula (PEG)X-(PPG)Y-(PEG)X and (PEO)X-(PPO)Y-(PEO)X. Each poloxamer name ends with an arbitrary code number, which is related to the average numerical values of the respective monomer units denoted by X and Y.
  • The term “poloxamine” denotes a polyalkoxylated symmetrical block copolymer of ethylene diamine conforming to the general type [(PEG)X-(PPG)Y]2-NCH2CH2N-[(PPG)Y-(PEG)X]2. Each Poloxamine name is followed by an arbitrary code number, which is related to the average numerical values of the respective monomer units denoted by X and Y.
  • The term “inverse thermosensitive polymer” as u sed herein refers to a polymer that is soluble in water at ambient temperature, but at least partially phase-separates out of water at physiological temperature. Inverse thermosensitive polymers include poloxamer 407, poloxamer 188, Pluronic® F127, Pluronic® F68, poly(N-isopropylacrylamide), poly(methyl vinyl ether), poly(N-vinylcaprolactam); and certain poly(organophosphazenes). See Bull. Korean Chem. Soc. 2002, 23, 549-554.
  • The phrase “polydispersity index” refers to the ratio of the “weight average molecular weight” to the “number average molecular weight” for a particular polymer; it reflects the distribution of individual molecular weights in a polymer sample.
  • The phrase “weight average molecular weight” refers to a particular measure of the molecular weight of a polymer. The weight average molecular weight is calculated as follows: determine the molecular weight of a number of polymer molecules; add the squares of these weights; and then divide by the total weight of the molecules.
  • The phrase “number average molecular weight” refers to a particular measure of the molecular weight of a polymer. The number average molecular weight is the common average of the molecular weights of the individual polymer molecules. It is determined by measuring the molecular weight of n polymer molecules, summing the weights, and dividing by n.
  • The term “concretion” denotes a mass or nodule of solid matter formed by growing together, by congelation, condensation, coagulation, induration, etc. Common synonyms, for example, are stones, clots, tones, lumps or calculi. Often, biologically, a concretion is a hard lump of mineral salts found in a hollow organ or duct of the body. In one embodiment, concretion refers to stone-like objects found within a body organ (e.g., the kidneys).
  • The term “lumen” denotes the space enclosed by a tube-like structure or hollow organ, such as inside an artery, a vein, a kidney, a gall bladder, a ureter, a urinary bladder, a pancreas, a salivary gland, a small intestine or a large intestine (i.e., an opening, space, or cavity in a biological system).
  • Concretions
  • Concretions can develop in certain parts of the body, such as in the kidneys, pancreas, ureter and gallbladder. It is not uncommon for biological concretions to be referred to as calculi or stones, especially when they are composed of mineral salts. For example, concretions formed in the biliary system are called gallstones. Those that form in the bladder are as also known as vesical calculi or bladder stones, and cystoliths. Calculi occurring in the kidney are often called kidney stones. Calculi can also occur in the ureter and are usually the result of the passage of one originating in the kidney. Calculi of the urinary bladder; also known as vesical calculi or bladder stones, and cystoliths. It is also possible to observe the presence of calculi in a salivary ducts or glands.
  • There are four main types of calculi observed biologically. The majority of calculi, about 75%, are calcium-containing, composed of calcium oxalate, sometimes mixed with calcium phosphate. Another 15% are composed of magnesium ammonium phosphate; these calculi are often referred to as “triple stones” or struvite stones. The bulk of the remaining stones are made up of uric acid or cystine. When these calculi are too large to pass spontaneously, medical intervention is often needed.
  • Lithotripsy
  • Larger biological concretions often need to be shattered because their size prohibits non-surgical removal from the body. This procedure is known as lithotripsy. Shattering a concretion (by, for example, light, chemical, or physical energy) will disperse the resulting fragments from the original location of the concretion. It is important to remove all the fragments, as fragments that are not removed from the body can form the nuclei for the formation of new concretions. This process is made difficult by the fact that often the shattering process can cause fragments to move into inaccessible or unknown areas of the body thus preventing or interfering with the capture and removal of the fragments.
  • It is common to refer to lithotripsy with respect to where the energy is generated. Extracorporeal lithotripsy is where the energy needed is generated outside the body; intracorporeal lithotripsy is where the energy needed is generated inside the body; both methods are discussed in more detail below.
  • Extracorporeal Lithotripsy
  • In one embodiment, energy transferred to fragment a concretion may emanate from outside the patient's body, from a lithotriptor for example, and travel through the patient's body until reaching the concretion targeted for fragmentation in a process called extracorporeal shock wave lithotripsy (ESWL). ESWL is a method of stone fragmentation commonly used to treat kidney stone disease. Various lithotriptors and methods exist for generating high-intensity, focused shock waves for the fragmentation of objects, such as kidney stones, inside a human being and confined in a body liquid. A lithotriptor generating a spark gap discharge in water has been used to generate a shock wave within an ellipsoidal reflector, which couples and focuses the shock wave to fragment kidney stones inside the patient's body. Lithotriptors also exist that use a coil and a mating radiator, in the form of a spherical segment, to produce magnetically induced self-converging shock waves that can be directed at a stone within the patient's body. A lithotriptor also exists that features piezoelectric elements arranged in mosaic form on a spheroidal cap have also been used to produce focused high-intensity shock waves at the geometric center of the cap, where the concretion must be placed.
  • The treatment of concretion ailments by means of an extracorporeal lithotripsy apparatus requires some means, such an ultrasound locating system, for correctly positioning the lithotripsy apparatus and the patient relative to each other so that the concretion, such as a kidney stone, is located in the focus of the shock waves. The focused shock waves are then coupled into the body of the patient, and act on the concretion to disintegrate it into fragments, which can be naturally eliminated.
  • As mentioned above, a locating system is also needed to identifying the position of the concretion within the patient, such as an x-ray system or an ultrasound system. A visual display is provided by the locating system which includes a mark identifying the concretion and an indicator for the position of the focus. Devices of this type are utilized, for example, for disintegrating kidney stones in situ in the human body, and have the advantage of avoiding invasion of the body using instruments.
  • Intracorporeal Lithotripsy
  • Intracorporeal lithotripsy utilizes a probe advanced with the aim of endoscope and positioned in proximity to the concretion. The energy, required for fragmentation is transferred through the probe to the concretion and the treatment process is visualized during fragmentation. The mode of energy transfer may be different and accordingly the intracorporeal lithotripsy techniques are divided into following groups: ultrasonic, laser, electro-hydraulic and mechanic/ballistic impact.
  • The last group comprises, for example, detonating an explosive near the concretion and causing the shock wave generated by the explosion to act directly upon the concretion and crush it into pieces. An example of such technique is disclosed in U.S. Pat. No. 4,605,003, referring to a lithotriptor comprising an inner tube inserted within an outer slender tube and provided with an explosive layer or a gas-generating layer. By the blasting of the explosive layer or the gas-generating layer, the outer slender tube or the inner tube is caused to collide with the stone and crush it.
  • An example of mechanical impact technique can be found in U.S. Pat. No. 5,448,363 in which is disclosed an endoscopic lithotriptor provided with a hammer element to periodically strike the concretion. The hammer element is pneumatically driven by a linear jet of air causing it to swing through an arc about a pivot to impact an anvil. There are known also many other patents, disclosing lithotriptors, which operation is based on mechanic/ballistic principle, e.g. U.S. Pat. No. 5,722,980 and U.S. Pat. No. 6,261,298.
  • An example of laser technique is described in U.S. Pat. No. 4,308,905, concerning multi-purpose lithotriptor, equipped with laser light-conducting fibers, through which the energy required for crushing the concretion is conducted.
  • Ultrasonic technique is relatively popular and because of its safety and usefulness is widely accepted. According to this principle ultrasound probe emits high-frequency ultrasonic energy that has a disruption effect upon direct exposure to the concretion. Direct contact of the probe tip and stone is essential for effectiveness of ultrasonic lithotripsy. This technique is implemented in many lithotriptors, e.g. as described in U.S. Pat. No. 6,149,656.
  • In addition there is electro-hydraulic technique, which utilizes electric discharge, ignited between two electrodes disposed within the probe and producing shock wave, expanding towards the concretion through liquid phase, which surrounds the concretion. In the literature electro-hydraulic lithotripsy is defined as the oldest form of “power” lithotripsy. The electro-hydraulic lithotriptor releases high-energy impulse discharges from an electrode at the tip of a flexible probe, which is placed next to the stone. It is considered a highly effective means of bladder stone shattering and has become an accepted practice for this use. Since the shock waves generated during electro-hydraulic lithotripsy treatment are of sufficient force the probe must not be used 5 mm or closer to soft tissues otherwise severe damage will result. Since the discharge takes place within liquid phase the concretion is destroyed by virtue of combination of energy of the shock wave, caused by the discharge, hydraulic pressure of the surrounding liquid and collision of fragments in the liquid flow.
  • Problems with Conventional Lithotripsy
  • It can be easily appreciated that in lithotripsy the energy is transferred indirectly to the concretion via a liquid medium. Therefore the amount of energy required for fragmentation must be sufficient to overcome the strength of the concretion, to cause its fragmentation, after the energy has been delivered through the working liquid. For a concretion encased in a polymer matrix, even more additional energy will be needed. Unfortunately, release of such high levels of energy by producing shock waves might be harmful to the adjacent tissues and therefore potentially dangerous for the patient.
  • Another problem of almost all lithotriptors that are intended for destroying concretions by bringing mechanical energy of impact or shock wave is the fact that the stone is usually “displaced” with each pulse of energy, leaving the previous place and being “thrown” to another one. This renders the operation complicate and may cause mechanical damage to the surrounding tissue. The instant invention solves both of these problems.
  • Methods of the Invention
  • The present invention improves significantly the success rate of lithotripsy and reduces the risk of tissue damage, by injecting temporary plugs in front and behind a concretion (external shock wave lithotripsy) or behind a concretion (intracorporeal lithotripsy) prior to the fragmentation of the concretion. The plugs in both applications consist of an aqueous solution of inverse thermosensitive polymers. These polymer solutions are liquid below body temperature and gel at about body temperature. The polymer solution starts externally of the body and thus at a temperature below body temperature. The polymer solution may be further chilled to prolong the time the gel stays in the liquid form. A preferred temperature is about 10° C. below the gelation temperature of the polymer solution.
  • Introduction/Removal of the Plug
  • The polymer solution can be introduced through a catheter behind and in front of the concretion for extracorporeal shockwave lithotripsy approach, and just behind the concretion for the intracorporeal lithotripsy approach. In one embodiment, a catheter can be used to dispense one or more fluids other than or in addition to the inverse thermosensitive polymer. The catheter also can be a dilatation catheter with the ability also to dispense one or more fluids other than or in addition to the polymer. In one embodiment, the catheter is 3-10 French in size, and more preferably 3-6 French.
  • In another embodiment the catheter may be a triple lumen catheter with one lumen for the delivery of the polymer solution behind the kidney stone, one lumen for the delivery of the polymer solution in front of the kidney stone and one lumen for the delivery of other fluids like contrast agent solution, saline or for the delivery of a solution to dissolved the gel after the procedure.
  • In another embodiment, the syringe or other mechanism used to inject the inverse thermosensitive polymer in liquid form into the body can be, for example, a 1-100 cc syringe such as a syringe with volume of 1-50 cc or with a volume of 1-5 cc. Pressure applied to the syringe can be applied by hand or by an automated syringe pusher.
  • The gelation of reverse thermosensitive polymers is dependent on the temperature and the concentration of the polymer. Therefore, after the fragmentation procedure, the gel can be removed by instilling a fluid around the gel, which leads to dissolution of the gel. The fluid may be chilled to help in the dissolution with a preferred temperature of about 10° C. below the gelation temperature. The fluid can be instilled through a catheter or syringe percutaneously.
  • Inverse Thermosensitive Polymers
  • In general, the inverse thermosensitive polymers used in the methods of the invention, which become a gel at or about body temperature, can be injected into the patient's-body in a liquid form. The injected material once reaching body temperature undergoes a transition from a liquid to a gel. The inverse thermosensitive polymers used in connection with the methods of the invention may comprise a block copolymer with inverse thermal gelation properties. The block copolymer can further comprise a polyoxyethylene-polyoxypropylene block copolymer such as a biodegradable, biocompatible copolymer of polyethylene oxide and polypropylene oxide. Also, the inverse thermosensitive polymer can include a therapeutic agent such as an anti-angiogenic agent.
  • The molecular weight of the inverse thermosensitive polymer is preferably between 1,000 and 50,000, more preferably between 5,000 and 35,000. Preferably the polymer is in an aqueous solution. For example, typical aqueous solutions contain about 5% to about 30% polymer, preferably about 10% to about 25%. The molecular weight of a suitable inverse thermosensitive polymer (such as a poloxamer or poloxamine) may be, for example, between 5,000 and 25,000, and more particularly between 7,000 and 20,000.
  • The pH of the inverse thermosensitive polymer formulation administered to the mammal is, generally, about 6.0 to about 7.8, which are suitable pH levels for injection into the mammalian body. The pH level may be adjusted by any suitable acid or base, such as hydrochloric acid or sodium hydroxide.
  • Suitable inverse thermosensitive polymers include polyoxyethylene-polyoxypropylene (PEO-PPO) block copolymers. Two examples are Pluronic® F127 and F108, which are PEO-PPO block copolymers with molecular weights of 12,600 and 14,600, respectively. Each of these compounds is available from BASF of Mount Olive, N.J. Pluronic® F108 at 12-25% concentration in phosphate buffered saline (PBS) is an example of a suitable inverse thermosensitive polymeric material. Pluronic® acid F127 at 12-25% concentration in PBS is another example of a suitable material. Low concentrations of dye (such as crystal violet), hormones, therapeutic agents, fillers, and antibiotics can be added to the inverse thermosensitive polymer. In general, other biocompatible, biodegradable PEO-PPO block copolymers that exist as a gel at body temperature and a liquid at below body temperature may also be used according to the present invention.
  • Notably, Pluronic® polymers have unique surfactant abilities and extremely low toxicity and immunogenic responses. These products have low acute oral and dermal toxicity and low potential for causing irritation or sensitization, and the general chronic and sub-chronic toxicity is low. In fact, Pluronic® polymers are among a small number of surfactants that have been approved by the FDA for direct use in medical applications and as food additives (BASF (1990) Pluronic® & Tetronic® Surfactants, BASF Co., Mount Olive, N.J.). Recently, several Pluronic® polymers have been found to enhance the therapeutic effect of drugs, and the gene transfer efficiency mediated by adenovirus. (March K L, Madison J E, Trapnell B C. “Pharmacokinetics of adenoviral vector-mediated gene delivery to vascular smooth muscle cells: modulation by poloxamer 407 and implication for cardiovascular gene therapy” Hum Gene Therapy 1995, 6, 41-53).
  • The average molecular weights of the poloxamers range from about 1,000 to greater than 16,000 daltons. Because the poloxamers are products of a sequential series of reactions, the molecular weights of the individual poloxamer molecules form a statistical distribution about the average molecular weight. In addition, commercially available poloxamers contain substantial amounts of poly(oxyethylene) homopolymer and poly(oxyethylene)/poly(oxypropylene diblock polymers. The relative amounts of these byproducts increase as the molecular weights of the component blocks of the poloxamer increase. Depending upon the manufacturer, these byproducts may constitute from about 15 to about 50% of the total mass of the polymer.
  • The inverse thermosensitive polymers may be purified using a process for the fractionation of water-soluble polymers, comprising the steps of dissolving a known amount of the polymer in water, adding a soluble extraction salt to the polymer solution, maintaining the solution at a constant optimal temperature for a period of time adequate for two distinct phases to appear, and separating physically the phases. Additionally, the phase containing the polymer fraction of the preferred molecular weight may be diluted to the original volume with water, extraction salt may be added to achieve the original concentration, and the separation process repeated as needed until a polymer having a narrower molecular weight distribution than the starting material and optimal physical characteristics can be recovered.
  • In certain embodiments, a purified poloxamer or poloxamine has a polydispersity index from about 1.5 to about 1.0. In certain embodiments, a purified poloxamer or poloxamine has a polydispersity index from about 1.2 to about 1.0. In certain embodiments, a purified poloxamer or poloxamine has a polydispersity index from about 1.1 to about 1.0.
  • The aforementioned process consists of forming an aqueous two-phase system composed of the polymer and an appropriate salt in water. In such a system, a soluble salt can be added to a single phase polymer-water system to induce phase separation to yield a high salt, low polymer bottom phase, and a low salt, high polymer upper phase. Lower molecular weight polymers partition preferentially into the high salt, low polymer phase. Polymers that can be fractionated using this process include polyethers, glycols such as poly(ethylene glycol) and poly(ethylene oxide)s, polyoxyalkylene block copolymers such as poloxamers, poloxamines, and polyoxypropylene/polyoxybutylene copolymers, and other polyols, such as polyvinyl alcohol. The average molecular weight of these polymers may range from about 800 to greater than 100,000 daltons. See U.S. Pat. No. 6,761,824. The aforementioned purification process inherently exploits the differences in size and polarity, and therefore solubility, among the poloxamer molecules, the poly(oxyethylene) homopolymer and the poly(oxyethylene)/poly(oxypropylene) diblock byproducts. The polar fraction of the poloxamer, which generally includes the lower molecular weight fraction and the byproducts, is removed allowing the higher molecular weight fraction of poloxamer to be recovered. The larger molecular weight poloxamer recovered by this method has physical characteristics substantially different from the starting material or commercially available poloxamer including a higher average molecular weight, lower polydispersity and a higher viscosity in aqueous solution.
  • Other purification methods may be used to achieve the desired outcome. For example, WO 92/16484 discloses the use of gel permeation chromatography to isolate a fraction of poloxamer 188 that exhibits beneficial biological effects, without causing potentially deleterious side effects. The copolymer thus obtained had a polydispersity index of 1.07 or less, and was substantially saturated. The potentially harmful side effects were shown to be associated with the low molecular weight, unsaturated portion of the polymer, while the medically beneficial effects resided in the uniform higher molecular weight material. Other similarly improved copolymers were obtained by purifying either the polyoxypropylene center block during synthesis of the copolymer, or the copolymer product itself (e.g., U.S. Pat. No. 5,523,492 and U.S. Pat. No. 5,696,298).
  • Further, a supercritical fluid extraction technique has been used to fractionate a polyoxyalkylene block copolymer as disclosed in U.S. Pat. No. 5,567,859. A purified fraction was obtained, which was composed of a fairly uniform polyoxyalkylene block copolymer having a polydispersity of less than 1.17. According to this method, the lower molecular weight fraction was removed in a stream of carbon dioxide maintained at a pressure of 2200 pounds per square inch (psi) and a temperature of 40° C.
  • Additionally, U.S. Pat. No. 5,800,711 discloses a process for the fractionation of polyoxyalkylene block copolymers by the batchwise removal of low molecular weight species using a salt extraction and liquid phase separation technique. Poloxamer 407 and poloxamer 188 were fractionated by this method. In each case, a copolymer fraction was obtained which had a higher average molecular weight and a lower polydispersity index as compared to the starting material. However, the changes in polydispersity index were modest and analysis by gel permeation chromatography indicated that some low-molecular-weight material remained. The viscosity of aqueous solutions of the fractionated polymers was significantly greater than the viscosity of the commercially available polymers at temperatures between 10° C. and 37° C., an important property for some medical and drug delivery applications. Nevertheless, some of the low molecular weight contaminants of these polymers are thought to cause deleterious side effects when used inside the body, making it especially important that they be removed in the fractionation process. As a consequence, polyoxyalkylene block copolymers fractionated by this process are not appropriate for all medical uses.
  • In a preferred embodiment, the polymers used are block polymers such as polyoxyethylene-polyoxypropylene (PEO-PPO) block polymers of the general structure A-B, (A-B)n, A-B-A (e.g., Pluronic®), or (A-B-A)n with A being the PEO part and B being the PPO part and n being greater than 1. In another preferred embodiment, the polymers used are branched polymers of polyoxyethylene-polyoxypropylene (PEO-PPO) like tetra-functional poloxamines (e.g., Tetronic®).
  • EXEMPLIFICATION Example 1 Gelation Temperature of Selected Pluronic® and Tetronic® Polymer Solutions
  • The polymer was weighed into a plastic tube. To achieve the required concentration the weight was multiplied by 4, for 25 weight percent (w %), and by 5, for 20 weight percent (w %), and the required final weight was achieved by adding saline. The solutions were placed in the fridge at 4° C. and usually were ready the next morning. Gelation points were measures in a Brookfield viscometer and the point at which viscosity exceeded the range of the plate/cone (>102,000 cP) was called the gelation temperature.
    TABLE 1
    Gelation Temperature of Selected Inverse Thermosensitive Polymer
    Solutions in Saline
    polymer concentration temperature
    Tetronic 1107 25 w %   27° C.
    Tetronic 1107 20 w %   34° C.
    Purified Tetronic 1107 25 w %   22° C.
    Purified Tetronic 1107 20 w % 32.5° C.
    Tetronic 1307 25 w % 24.5° C.
    Tetronic 1307 20 w %   31° C.
    Purified Tetronic 1307 25 w %   20° C.
    Purified Tetronic 1307 20 w %   26° C.
    Pluronic F108 25 w %   26° C.
    Pluronic F108 20 w %   60° C.
    Purified Pluronic F108 25 w %   19° C.
    Purified Pluronic F108 20 w %   26° C.
  • Example 2 Gelation Temperature of Selected Pluronic® and Tetronic® Polymer Solutions with Iodinated Contrast Agent
  • Purified polymers were weighed into 50 mL centrifuge tubes and a 1:1 mixture of saline and 100% Omnipaque 300 were added until a specific weight percentage was reached. Gelation points were measured in a Brookfield viscometer and the point at which the viscosity exceeded the range of the plate/cone (>102,000 cP) was called the gelation point. All solutions were further heated to 37° C. to ascertain that the material still exceeded the viscosity range and remained a gel. All gels passed.
    TABLE 2
    Gelation Temperature of Purified Inverse Thermosensitive Polymer
    Solutions containing 50 w % Omnipaque 300
    polymer concentration temperature
    Purified Tetronic 1107 20 w %   24° C.
    Purified Tetronic 1307 21 w % 26.5° C.
    Purified Pluronic F108 18 w % 21.5° C.
    Purified Pluronic F127 18 w %   18° C.
  • Example 3 Plastic Tube Experiments
  • A plastic tube with an inner diameter of 0.9 cm was used as a mimic of a ureter. The tube was partially filled with saline and the kidney stone placed into the middle of the tube. A ureteroscope was placed inside the tube close to the stone and cold polymer solutions were injected behind the stone. The stone was fragmented using either electro-hydraulic lithotripsy or laser lithotripsy. Various inverse thermosensitive polymer solutions such as purified Pluronic F108 (poloxamer 338), Pluronic F127 (poloxamer 407) and Tetronic 1307, were tested in this set-up in concentrations ranging from 15 to 25 w %. In all cases, the stone could be fragmented into smaller particles and the gel captures all fragments. The lower polymer concentrations (15 w %) resulted in rather soft gels, while the higher polymer concentrations (25 w %) were difficult to deploy due to the increased viscosity of the polymer solution and early onset of gelation.
  • Example 4 Pig Ureter Experiments
  • Pig ureters (approximately 25 cm in length) were fixed to a tray and the tray submerged in a water bath heated to 37° C. A sheath was inserted into the ureter and a small (approximately 5 mm) Plaster of Paris kidney stone mimic was advanced into the ureter through the sheath using a stone basket. A 3F catheter was advanced through the working channel of the ureteroscope approximately 3 cm behind the stone and 1.5 mL of a 20 w % purified Pluronic F127 (poloxamer 407) solution was injected. The poloxamer gel was colored blue with methylene blue. Irrigation of the ureter was accomplished with room temperature saline at a flow rate of approximately 5 mL/minute. Very little dilution of the gel was observed during the 20 minutes of irrigation as the gelation temperature of the gel is about 15° C. Dissolution was easily accomplished by injection into the gel with either room temperature saline or cold water. The cold water required less volume to dissolve the gel than the room temperature saline (20 mL vs. 35 mL).
  • Example 5 In Vivo Experiments
  • Independently two adult female pigs were anesthetized. In each a lower midline incision was made, the left ureter isolated, a ureterotomy performed adjacent to the bladder and a guide wire was advanced up the ureter to the kidney. A stone was then pushed up the ureter to approximately 10 cm proximal to the ureterotomy. A rigid ureteroscope (Stortz) was passed up the ureter, the stone visualized, a 3 French catheter passed through the ureteroscope beyond the stone, a cooled 20 w % solution of purified poloxamer 407 injected, the catheter removed and the electro hydraulic probe passed to the stone through the ureteroscope. The stone was successfully fragmented with no fragments progressing proximally. The ureter was surgically removed, and pathological examination revealed a reactive epithelium consistent with manipulation by the ureteroscope. The animals were euthanized. In sum, in both experiments, the stones were successfully fragmented without any discernable untoward effects to the ureters.
  • Incorporation by Reference
  • All of the U.S. patents and U.S. patent application publications cited herein are hereby incorporated by reference.
  • Equivalents
  • Those skilled in the art will recognize, or be able to ascertain using no more than routine experimentation, many equivalents to the specific embodiments of the invention described herein. Such equivalents are intended to be encompassed by the following claims.

Claims (42)

  1. 1. A method of lithotripsy comprising the steps of:
    injecting a first composition, comprising an inverse thermosensitive polymer, into a lumen of a mammal, at a first distance from a concretion, wherein said first composition does not contact said concretion;
    optionally injecting a second composition, comprising an inverse thermosensitive polymer, into said lumen, at a second distance from said concretion, wherein said second composition is placed on the approximately opposite side of said concretion relative to said first composition, wherein said second composition does not contact said concretion; and
    directing energy to said concretion causing the fragmentation of said concretion into a plurality of fragments.
  2. 2. The method of claim 1, wherein said inverse thermosensitive polymer is a block copolymer, random copolymer, graft polymer, or branched copolymer.
  3. 3. The method of claim 1, wherein said inverse thermosensitive polymer is a block polymer or a branched copolymer.
  4. 4. The method of claim 1, wherein said inverse thermosensitive polymer is an optionally purified poloxamer or poloxamine.
  5. 5. The method of claim 1, wherein said inverse thermosensitive polymer is optionally purified and selected from the group consisting of poloxamine 1107, poloxamine 1307, poloxamer 338 and poloxamer 407.
  6. 6. The method of claim 1, wherein said inverse thermosensitive polymer is an optionally purified poloxamer 407.
  7. 7. The method of claim 1, wherein said inverse thermosensitive polymer solution has a transition temperature of between about 10° C. and 40° C.
  8. 8. The method of claim 1, wherein said inverse thermosensitive polymer solution has a transition temperature of between about 15° C. and 30° C.
  9. 9. The method of claim 1, wherein said inverse thermosensitive polymer solution has a transition temperature of about 25° C.
  10. 10. The method of claim 1, wherein said first distance is between about 1 cm and about 5 cm.
  11. 11. The method of claim 1, wherein said first distance is between about 2 cm and about 4 cm.
  12. 12. The method of claim 1, wherein said first distance is about 3 cm.
  13. 13. The method of claim 1, wherein said second distance is between about 1 cm and about 5 cm.
  14. 14. The method of claim 1, wherein said second distance is between about 2 cm and about 4 cm.
  15. 15. The method of claim 1, wherein said second distance is about 3 cm.
  16. 16. The method of claim 1, wherein said composition is injected into said lumen through a percutaneous access device.
  17. 17. The method of claim 1, wherein said composition is injected into said lumen through a catheter or a syringe.
  18. 18. The method of claim 17, wherein the catheter is a dual lumen catheter or a triple lumen catheter.
  19. 19. The method of claim 1, wherein said energy is an acoustic shock wave, a pneumatic pulsation, an electrical hydraulic shock wave, or a laser beam.
  20. 20. The method of claim 1, wherein said lumen is, or is part of, a kidney, a gall bladder, a ureter, a urinary bladder, a pancreas, a salivary gland, a small intestine or a large intestine.
  21. 21. The method of claim 1, wherein said lumen is, or is part of, the ureter or kidney.
  22. 22. The method of claim 1, wherein said concretion is a kidney stone, pancreatic stone, salivary stone, or biliary stone.
  23. 23. The method of claim 1, wherein said concretion is a kidney stone.
  24. 24. The method of claim 1, wherein said mammal is a human.
  25. 25. The method of claim 1, wherein said composition comprises about 5% to about 30% of said inverse thermosensitive polymer.
  26. 26. The method of claim 1, wherein said composition comprises about 10% to about 25% said inverse thermosensitive polymer.
  27. 27. The method of claim 1, wherein said composition comprising an inverse thermosensitive polymer further comprises a contrast-enhancing agent.
  28. 28. The method of claim 27, wherein said contrast-enhancing agent is selected from the group consisting of radiopaque materials, paramagnetic materials, heavy atoms, transition metals, lanthanides, actinides, dyes, and radionuclide-containing materials.
  29. 29. The method of claim 1, wherein the inverse thermosensitive polymer has a polydispersity index from about 1.5 to 1.0.
  30. 30. The method of claim 1, wherein the inverse thermosensitive polymer has a polydispersity index from about 1.2 to 1.0.
  31. 31. The method of claim 1, wherein the inverse thermosensitive polymer has a polydispersity index from about 1.1 to 1.0.
  32. 32. The method of claim 1, wherein said inverse thermosensitive polymer is an optionally purified poloxamer or poloxamine; and said inverse thermosensitive polymer solution has a transition temperature of between about 10° C. and 40° C.
  33. 33. The method of claim 1, wherein said inverse thermosensitive polymer is an optionally purified poloxamer or poloxamine; and said inverse thermosensitive polymer solution has a transition temperature of between about 15° C. and 30° C.
  34. 34. The method of claim 1, wherein said inverse thermosensitive polymer is an optionally purified poloxamer or poloxamine; and said inverse thermosensitive polymer solution has a transition temperature of about 25° C.
  35. 35. The method of claim 1, wherein said energy is an acoustic shock wave, a pneumatic pulsation, an electrical hydraulic shock wave, or a laser beam; and said lumen is, or is part of, a kidney, a gall bladder, a ureter, a urinary bladder, a pancreas, a salivary gland, a small intestine or a large intestine.
  36. 36. The method of claim 1, wherein said inverse thermosensitive polymer is optionally purified and selected from the group consisting of poloxamine 1107, poloxamine 1307, poloxamer 338 and poloxamer 407; and said lumen is, or is part of, a kidney, a gall bladder, a ureter, a urinary bladder, a pancreas, a salivary gland, a small intestine or a large intestine.
  37. 37. The method of claim 1, wherein said inverse thermosensitive polymer is optionally purified poloxamer 407; and said lumen is, or is part of, the ureter or kidney.
  38. 38. The method of claim 1, wherein said inverse thermosensitive polymer is optionally purified and selected from the group consisting of poloxamine 1107, poloxamine 1307, poloxamer 338 and poloxamer 407; wherein said energy is an acoustic shock wave, a pneumatic pulsation, an electrical hydraulic shock wave, or a laser beam; and said lumen is, or is part of, a kidney, a gall bladder, a ureter, a urinary bladder, a pancreas, a salivary gland, a small intestine or a large intestine.
  39. 39. The method of claim 1, wherein said inverse thermosensitive polymer is an optionally purified poloxamer or poloxamine; said inverse thermosensitive polymer solution has a transition temperature of between about 10° C. and 40° C.; said energy is an acoustic shock wave, a pneumatic pulsation, an electrical hydraulic shock wave, or a laser beam; and said lumen is, or is part of, a kidney, a gall bladder, a ureter, a urinary bladder, a pancreas, a salivary gland, a small intestine or a large intestine.
  40. 40. The method of claim 1, wherein said inverse thermosensitive polymer is an optionally purified poloxamer or poloxamine; wherein said inverse thermosensitive polymer solution has a transition temperature of between about 15° C. and 30° C.; said energy is an acoustic shock wave, a pneumatic pulsation, an electrical hydraulic shock wave, or a laser beam; and said lumen is, or is part of, a kidney, a gall bladder, a ureter, a urinary bladder, a pancreas, a salivary gland, a small intestine or a large intestine.
  41. 41. The method of claim 1, wherein said inverse thermosensitive polymer is an optionally purified poloxamer or poloxamine; said inverse thermosensitive polymer solution has a transition temperature of about 25° C.; said energy is an acoustic shock wave, a pneumatic pulsation, an electrical hydraulic shock wave, or a laser beam; and said lumen is, or is part of, a kidney, a gall bladder, a ureter, a urinary bladder, a pancreas, a salivary gland, a small intestine or a large intestine.
  42. 42. The method of claim 1, wherein said inverse thermosensitive polymer is an optionally purified poloxamer or poloxamine; said inverse thermosensitive polymer solution has a transition temperature of between about 10° C. and 40° C.; said energy is an electrical hydraulic shock wave; and said lumen is, or is part of, the ureter or kidney.
US10963410 2003-10-14 2004-10-12 Confinement of kidney-stone fragments during lithotripsy Abandoned US20050143678A1 (en)

Priority Applications (2)

Application Number Priority Date Filing Date Title
US51050503 true 2003-10-14 2003-10-14
US10963410 US20050143678A1 (en) 2003-10-14 2004-10-12 Confinement of kidney-stone fragments during lithotripsy

Applications Claiming Priority (5)

Application Number Priority Date Filing Date Title
US10963410 US20050143678A1 (en) 2003-10-14 2004-10-12 Confinement of kidney-stone fragments during lithotripsy
US12946478 US8409218B2 (en) 2003-10-14 2010-11-15 Confinement of kidney stone fragments during lithotripsy
US13779415 US8998928B2 (en) 2003-10-14 2013-02-27 Confinement of kidney stone fragments during lithotripsy
US14631608 US20160015393A1 (en) 2003-10-14 2015-02-25 Confinement of kidney stone fragments during lithotripsy
US15149885 US20170086849A1 (en) 2003-10-14 2016-05-09 Confinement Of Kidney Stone Fragments During Lithotripsy

Related Child Applications (1)

Application Number Title Priority Date Filing Date
US12946478 Continuation US8409218B2 (en) 2003-10-14 2010-11-15 Confinement of kidney stone fragments during lithotripsy

Publications (1)

Publication Number Publication Date
US20050143678A1 true true US20050143678A1 (en) 2005-06-30

Family

ID=34465137

Family Applications (5)

Application Number Title Priority Date Filing Date
US10963410 Abandoned US20050143678A1 (en) 2003-10-14 2004-10-12 Confinement of kidney-stone fragments during lithotripsy
US12946478 Active US8409218B2 (en) 2003-10-14 2010-11-15 Confinement of kidney stone fragments during lithotripsy
US13779415 Active US8998928B2 (en) 2003-10-14 2013-02-27 Confinement of kidney stone fragments during lithotripsy
US14631608 Abandoned US20160015393A1 (en) 2003-10-14 2015-02-25 Confinement of kidney stone fragments during lithotripsy
US15149885 Abandoned US20170086849A1 (en) 2003-10-14 2016-05-09 Confinement Of Kidney Stone Fragments During Lithotripsy

Family Applications After (4)

Application Number Title Priority Date Filing Date
US12946478 Active US8409218B2 (en) 2003-10-14 2010-11-15 Confinement of kidney stone fragments during lithotripsy
US13779415 Active US8998928B2 (en) 2003-10-14 2013-02-27 Confinement of kidney stone fragments during lithotripsy
US14631608 Abandoned US20160015393A1 (en) 2003-10-14 2015-02-25 Confinement of kidney stone fragments during lithotripsy
US15149885 Abandoned US20170086849A1 (en) 2003-10-14 2016-05-09 Confinement Of Kidney Stone Fragments During Lithotripsy

Country Status (4)

Country Link
US (5) US20050143678A1 (en)
EP (1) EP1682014A4 (en)
JP (1) JP4898447B2 (en)
WO (1) WO2005037062A3 (en)

Cited By (29)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20060020269A1 (en) * 2004-07-20 2006-01-26 Eric Cheng Device to aid in stone removal and laser lithotripsy
US20060135725A1 (en) * 2004-12-21 2006-06-22 Scimed Life Systems, Inc. New balloon materials
US20070016244A1 (en) * 2005-07-06 2007-01-18 Percutaneous Systems, Inc. Methods and apparatus for deploying ureteral stents
US20070185520A1 (en) * 2006-02-07 2007-08-09 Boston Scientific Scimed, Inc. Detachable medical immobilization device and related methods of use
US20070191768A1 (en) * 2006-02-13 2007-08-16 Fossa Medical, Inc. Methods and Apparatus for Temporarily Occluding Body Lumens
US20080045985A1 (en) * 2006-06-21 2008-02-21 The Board Of Trustees Of The Leland Stanford Junior University Compositions and methods for joining non-conjoined lumens
US20080103481A1 (en) * 2006-09-29 2008-05-01 Pluromed, Inc. Methods for Preventing Retropulsion of Concretions and Fragments During Lithotripsy
US20080177277A1 (en) * 2004-07-07 2008-07-24 Percutaneous Systems, Inc. Methods for removing kidney stones from the ureter
US20090162438A1 (en) * 2007-12-20 2009-06-25 Synvascular, Inc. Compositions and methods for joining non-conjoined lumens
US20090187199A1 (en) * 2006-06-21 2009-07-23 The Board Of Trustees Of The Leland Stanford Junior University Compositions and methods for joining non-conjoined lumens
US20090287238A1 (en) * 2004-07-07 2009-11-19 Percutaneous Systems, Inc. Methods and apparatus for deploying short length ureteral stents
US20100204718A1 (en) * 2009-02-06 2010-08-12 Synvascular, Inc. Compositions and methods for joining non-conjoined lumens
US20130237967A1 (en) * 2011-09-10 2013-09-12 Cook Medical Technologies Llc Suction Lithotripsy Apparatus, Method and Kit
US8608760B2 (en) 2006-06-21 2013-12-17 The Board Of Trustees Of The Leland Stanford Junior University Compositions and methods for joining non-conjoined lumens
US20140276924A1 (en) * 2013-03-15 2014-09-18 Boston Scientific Scimed, Inc. Gel sweeper for residual stone fragment removal
US8845599B2 (en) 2011-07-11 2014-09-30 Boston Scientific Scimed, Inc. Medical procedures, devices and kits for the formation and removal of plug-forming compositions
US8998928B2 (en) 2003-10-14 2015-04-07 Genzyme Corporation Confinement of kidney stone fragments during lithotripsy
US20150265298A1 (en) * 2014-03-21 2015-09-24 Terumo Kabushiki Kaisha Calculus retrieving/removing device and method
US20150265295A1 (en) * 2014-03-21 2015-09-24 Terumo Kabushiki Kaisha Calculus retrieving/removing device and method
US20150265297A1 (en) * 2014-03-21 2015-09-24 Terumo Kabushiki Kaisha Calculus retrieving/removing device and method
US20150265294A1 (en) * 2014-03-21 2015-09-24 Terumo Kabushiki Kaisha Calculus retrieving/removing device and method
US9161767B2 (en) 2005-05-02 2015-10-20 Genzyme Corporation Non-lithotripsic kidney-stone therapy
US20150305760A1 (en) * 2006-10-13 2015-10-29 University Of Washington Method and Apparatus to Detect the Fragmentation of Kidney Stones by Measuring Acoustic Scatter
CN105147723A (en) * 2015-09-07 2015-12-16 山东赛克赛斯药业科技有限公司 Temperature-sensitive gel preparation, preparation method thereof and application of temperature-sensitive gel preparation to preventing transfer of calculus in lithotripsy
US9360124B2 (en) 2013-03-15 2016-06-07 Cook Medical Technologies Llc Bi-directional valve device for selective control of fluid flow through multiple converging paths
US9539014B2 (en) * 2014-03-21 2017-01-10 Terumo Kabushiki Kaisha Calculus removing/retrieving device and method
US9636127B2 (en) * 2015-03-31 2017-05-02 Terumo Kabushiki Kaisha Method for retrieving objects from a living body
US9662097B2 (en) * 2015-03-31 2017-05-30 Terumo Kabushiki Kaisha Method for retrieving objects from a living body and expanding a narrowed region in the living body
RU2661014C2 (en) * 2014-09-02 2018-07-11 Нордсон Корпорейшн Device and method for fragmenting organo-mineral concretion

Families Citing this family (12)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7907991B2 (en) * 2005-03-02 2011-03-15 C. R. Bard, Inc. System and method for marking body cavities
JP2010512230A (en) * 2006-12-11 2010-04-22 ザ レイヒー クリニック インコーポレイテッドThe Lahey Clinic, Inc. Perfused organs hemostasis
WO2009070793A1 (en) * 2007-11-29 2009-06-04 Pluromed, Inc. Endoscopic mucosal resectioning using purified inverse thermosensitive polymers
CA2869713A1 (en) 2012-04-12 2013-10-17 Ams Research Corporation Surgical laser systems and laser lithotripsy techniques
DE202013012287U1 (en) 2013-04-23 2016-01-18 Fraunhofer-Gesellschaft zur Förderung der angewandten Forschung e.V. Gel-forming system for the removal of kidney stone fragments
DE202013012275U1 (en) 2013-04-23 2015-12-18 Fraunhofer-Gesellschaft zur Förderung der angewandten Forschung e.V. Kit for producing a cross-linked gel for enclosing kidney stones, and / or kidney stone fragments
EP2796101B1 (en) 2013-04-23 2016-04-20 Fraunhofer-Gesellschaft zur Förderung der angewandten Forschung e.V. Kit for producing a cross-linked gel for encapsulating kidney stones and/or kidney stone fragments
ES2577102T3 (en) 2013-04-23 2016-07-13 Fraunhofer-Gesellschaft zur Förderung der angewandten Forschung e.V. gelling system to remove fragments of kidney stones
US9282985B2 (en) 2013-11-11 2016-03-15 Gyrus Acmi, Inc. Aiming beam detection for safe laser lithotripsy
US9254075B2 (en) 2014-05-04 2016-02-09 Gyrus Acmi, Inc. Location of fragments during lithotripsy
US9259231B2 (en) 2014-05-11 2016-02-16 Gyrus Acmi, Inc. Computer aided image-based enhanced intracorporeal lithotripsy
CN106037864A (en) * 2016-07-21 2016-10-26 李勇 Plugging device capable of injecting hydrogel for ureteroscope lithotripsy

Citations (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4608979A (en) * 1984-02-22 1986-09-02 Washington Research Foundation Apparatus for the noninvasive shock fragmentation of renal calculi
US4696297A (en) * 1985-02-27 1987-09-29 Farco-Pharma Gmbh Process for collecting fragments which are obtained on shattering stones in body cavities of living humans and other mammals
US5403324A (en) * 1994-01-14 1995-04-04 Microsonic Engineering Devices Company, Inc. Flexible catheter with stone basket and ultrasonic conductor
US5860972A (en) * 1995-10-26 1999-01-19 Xintec Corporation Method of detection and destruction of urinary calculi and similar structures
US20020120237A1 (en) * 2001-02-28 2002-08-29 Ronald Sahatjian Immobilizing objects in the body
US20040266983A1 (en) * 2000-08-17 2004-12-30 Reeve Lorraine E Purified polyoxyalkylene block copolymers
US20050175702A1 (en) * 2002-06-01 2005-08-11 Muller-Schulte Detlef P. Thermosensitive polymer carriers having a modifiable physical structure for biochemical analysis, diagnosis and therapy
US20050203498A1 (en) * 2002-02-15 2005-09-15 Celsion Corporation Method and apparatus treating tissue adjacent a bodily conduit with thermocompression and drugs

Family Cites Families (45)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4308905A (en) * 1980-03-24 1982-01-05 Nancy Gallagher Cover for air conditioner
JPS6158175B2 (en) * 1984-07-03 1986-12-10 Kyotofu
US4781677A (en) 1985-07-17 1988-11-01 Wilcox Gilbert M Method of treatment utilizing a double balloon nasobiliary occlusion catheter
US4845125A (en) 1987-11-10 1989-07-04 Indianapolis Center For Advanced Research, Inc. Chemolytic EDTA-citric acid composition for dissolution of calculi
US4979948A (en) 1989-04-13 1990-12-25 Purdue Research Foundation Method and apparatus for thermally destroying a layer of an organ
US5059200A (en) * 1990-04-06 1991-10-22 John Tulip Laser lithotripsy
WO1992016484A1 (en) 1991-03-19 1992-10-01 Cytrx Corporation Polyoxypropylene/polyoxyethylene copolymers with improved biological activity
US5696298A (en) * 1991-03-19 1997-12-09 Cytrx Corporation Polyoxypropylene/polyoxyethylene copolymers with improved biological activity
US5567859A (en) * 1991-03-19 1996-10-22 Cytrx Corporation Polyoxypropylene/polyoxyethylene copolymers with improved biological activity
US5129910A (en) 1991-07-26 1992-07-14 The Regents Of The University Of California Stone expulsion stent
EP0593741B2 (en) 1992-05-11 2004-10-27 Medical Innovations Corporation Improved biliary catheter
US5599300A (en) 1992-05-11 1997-02-04 Arrow Precision Products, Inc. Method for electrosurgically obtaining access to the biliary tree with an adjustably positionable needle-knife
US6770066B1 (en) 1992-05-11 2004-08-03 Ballard Medical Products Multi-lumen endoscopic catheter
US5843028A (en) 1992-05-11 1998-12-01 Medical Innovations Corporation Multi-lumen endoscopic catheter
US5536248A (en) 1992-05-11 1996-07-16 Arrow Precision Products, Inc. Method and apparatus for electrosurgically obtaining access to the biliary tree and placing a stent therein
EP1512398A1 (en) * 1997-03-31 2005-03-09 Boston Scientific Limited Intravascular stent with cytoskeletal inhibitors for the prevention of restenosis
US5401257A (en) 1993-04-27 1995-03-28 Boston Scientific Corporation Ureteral stents, drainage tubes and the like
US5448363A (en) * 1993-08-09 1995-09-05 Hager; Horst Food sorting by reflection of periodically scanned laser beam
US5531716A (en) 1993-09-29 1996-07-02 Hercules Incorporated Medical devices subject to triggered disintegration
JP3107488B2 (en) 1993-09-29 2000-11-06 株式会社資生堂 Sustained-release preparations and embolic agents with crosslinked hyaluronic acid
DE4405656C2 (en) * 1994-02-22 1998-12-10 Ferton Holding Means for removing calculi
US5860872A (en) 1996-03-07 1999-01-19 Vitale; Kevin Batter's stride training device
US5814006A (en) 1996-05-28 1998-09-29 Planz; Konrad Temporary stent in the urine path
US5855601A (en) 1996-06-21 1999-01-05 The Trustees Of Columbia University In The City Of New York Artificial heart valve and method and device for implanting the same
US5800711A (en) * 1996-10-18 1998-09-01 Mdv Technologies, Inc. Process for the fractionation of polyoxyalkylene block copolymers
US6261298B1 (en) * 1998-08-24 2001-07-17 Karl Storz-Gmbh & Co. Kg Device for concrement destruction or crushing
FR2781156B1 (en) * 1998-07-20 2001-06-29 Lafon Labor Pharmaceutical composition intended in particular for the prevention and treatment of radiation mucitis and chimiomucites
US6149656A (en) * 1998-09-11 2000-11-21 Volker Walz Electrodynamic lithotriptor
US6309384B1 (en) 1999-02-01 2001-10-30 Adiana, Inc. Method and apparatus for tubal occlusion
EP1154727B1 (en) 1999-02-19 2005-12-07 Boston Scientific Limited Laser lithotripsy device with suction
US6159220A (en) 1999-03-11 2000-12-12 Scimed Life Systems, Inc. Medical retrieval device
US6709465B2 (en) 1999-03-18 2004-03-23 Fossa Medical, Inc. Radially expanding ureteral device
US6214037B1 (en) 1999-03-18 2001-04-10 Fossa Industries, Llc Radially expanding stent
US7214229B2 (en) 1999-03-18 2007-05-08 Fossa Medical, Inc. Radially expanding stents
US6620172B1 (en) 1999-07-01 2003-09-16 Medsource Technologies, Inc. Entraining biological calculi
US6518871B2 (en) * 1999-12-29 2003-02-11 Robert B. Fennell Fuseholder remover
US7039453B2 (en) 2000-02-08 2006-05-02 Tarun Mullick Miniature ingestible capsule
US6440061B1 (en) 2000-03-24 2002-08-27 Donald E. Wenner Laparoscopic instrument system for real-time biliary exploration and stone removal
US6761824B2 (en) * 2000-08-17 2004-07-13 Reeve Lorraine E Process for the fractionation of polymers
US7041139B2 (en) 2001-12-11 2006-05-09 Boston Scientific Scimed, Inc. Ureteral stents and related methods
US6949125B2 (en) 2002-04-16 2005-09-27 Boston Scientific Scimed, Inc. Ureteral stent with end-effector and related methods
WO2005037062A3 (en) 2003-10-14 2006-03-23 Pluromed Inc Confinement of kidney-stone fragments during lithotripsy
US7052489B2 (en) 2003-12-05 2006-05-30 Scimed Life Systems, Inc. Medical device with deflecting shaft and related methods of manufacture and use
KR20080033159A (en) 2005-05-02 2008-04-16 더 제너럴 하스피탈 코포레이션 Non-lithotripsic kidney-stone therapy
EP1892231A1 (en) 2006-08-21 2008-02-27 Bayer Schering Pharma Aktiengesellschaft A large scale method for the deoxofluorination of ketones

Patent Citations (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4608979A (en) * 1984-02-22 1986-09-02 Washington Research Foundation Apparatus for the noninvasive shock fragmentation of renal calculi
US4696297A (en) * 1985-02-27 1987-09-29 Farco-Pharma Gmbh Process for collecting fragments which are obtained on shattering stones in body cavities of living humans and other mammals
US5403324A (en) * 1994-01-14 1995-04-04 Microsonic Engineering Devices Company, Inc. Flexible catheter with stone basket and ultrasonic conductor
US5860972A (en) * 1995-10-26 1999-01-19 Xintec Corporation Method of detection and destruction of urinary calculi and similar structures
US20040266983A1 (en) * 2000-08-17 2004-12-30 Reeve Lorraine E Purified polyoxyalkylene block copolymers
US20020120237A1 (en) * 2001-02-28 2002-08-29 Ronald Sahatjian Immobilizing objects in the body
US6565530B2 (en) * 2001-02-28 2003-05-20 Scimed Life Systems, Inc. Immobilizing objects in the body
US20050053662A1 (en) * 2001-02-28 2005-03-10 Scimed Life Systems, Inc. Immobilizing objects in the body
US20050203498A1 (en) * 2002-02-15 2005-09-15 Celsion Corporation Method and apparatus treating tissue adjacent a bodily conduit with thermocompression and drugs
US20050175702A1 (en) * 2002-06-01 2005-08-11 Muller-Schulte Detlef P. Thermosensitive polymer carriers having a modifiable physical structure for biochemical analysis, diagnosis and therapy

Cited By (49)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US8998928B2 (en) 2003-10-14 2015-04-07 Genzyme Corporation Confinement of kidney stone fragments during lithotripsy
US7883516B2 (en) * 2004-07-07 2011-02-08 Percutaneous Systems, Inc. Methods for removing kidney stones from the ureter
US8753351B2 (en) 2004-07-07 2014-06-17 Percutaneous Systems, Inc. Methods for removing kidney stones from the ureter
US8080019B2 (en) 2004-07-07 2011-12-20 Percutaneous Systems, Inc. Apparatus for deploying occluding structures in body lumens
US20090287238A1 (en) * 2004-07-07 2009-11-19 Percutaneous Systems, Inc. Methods and apparatus for deploying short length ureteral stents
US20080177277A1 (en) * 2004-07-07 2008-07-24 Percutaneous Systems, Inc. Methods for removing kidney stones from the ureter
US20110098690A1 (en) * 2004-07-07 2011-04-28 Percutaneous Systems, Inc. Methods for removing kidney stones from the ureter
US8911450B2 (en) 2004-07-07 2014-12-16 Percutaneous Systems, Inc. Methods and apparatus for deploying ureteral stents
US20060020269A1 (en) * 2004-07-20 2006-01-26 Eric Cheng Device to aid in stone removal and laser lithotripsy
US20060135725A1 (en) * 2004-12-21 2006-06-22 Scimed Life Systems, Inc. New balloon materials
US9968369B2 (en) 2005-05-02 2018-05-15 Genzyme Corporation Non-lithotripsic kidney-stone therapy
US9161767B2 (en) 2005-05-02 2015-10-20 Genzyme Corporation Non-lithotripsic kidney-stone therapy
US7972292B2 (en) 2005-07-06 2011-07-05 Percutaneous Systems, Inc. Methods and apparatus for deploying ureteral stents
US20070016244A1 (en) * 2005-07-06 2007-01-18 Percutaneous Systems, Inc. Methods and apparatus for deploying ureteral stents
US20070185520A1 (en) * 2006-02-07 2007-08-09 Boston Scientific Scimed, Inc. Detachable medical immobilization device and related methods of use
US8062282B2 (en) 2006-02-13 2011-11-22 Fossa Medical, Inc. Methods and apparatus for temporarily occluding body openings
US20070191768A1 (en) * 2006-02-13 2007-08-16 Fossa Medical, Inc. Methods and Apparatus for Temporarily Occluding Body Lumens
US8608760B2 (en) 2006-06-21 2013-12-17 The Board Of Trustees Of The Leland Stanford Junior University Compositions and methods for joining non-conjoined lumens
US20090187199A1 (en) * 2006-06-21 2009-07-23 The Board Of Trustees Of The Leland Stanford Junior University Compositions and methods for joining non-conjoined lumens
US8197499B2 (en) 2006-06-21 2012-06-12 The Board Of Trustees Of The Leland Stanford Junior University Compositions and methods for joining non-conjoined lumens
US8216259B2 (en) 2006-06-21 2012-07-10 The Board Of Trustees Of The Leland Stanford Jr. University Compositions and methods for joining non-conjoined lumens
US20080045985A1 (en) * 2006-06-21 2008-02-21 The Board Of Trustees Of The Leland Stanford Junior University Compositions and methods for joining non-conjoined lumens
US20080103481A1 (en) * 2006-09-29 2008-05-01 Pluromed, Inc. Methods for Preventing Retropulsion of Concretions and Fragments During Lithotripsy
CN106236181A (en) * 2006-09-29 2016-12-21 普拉罗美德公司 Methods for preventing retropulsion of concretions and fragments during lithotripsy
US20150305760A1 (en) * 2006-10-13 2015-10-29 University Of Washington Method and Apparatus to Detect the Fragmentation of Kidney Stones by Measuring Acoustic Scatter
US20090162438A1 (en) * 2007-12-20 2009-06-25 Synvascular, Inc. Compositions and methods for joining non-conjoined lumens
US8172861B2 (en) 2007-12-20 2012-05-08 Tautona Group, L.P. Compositions and methods for joining non-conjoined lumens
US20100204718A1 (en) * 2009-02-06 2010-08-12 Synvascular, Inc. Compositions and methods for joining non-conjoined lumens
US8563037B2 (en) 2009-02-06 2013-10-22 Tautona Group, L.P. Compositions and methods for joining non-conjoined lumens
US8845599B2 (en) 2011-07-11 2014-09-30 Boston Scientific Scimed, Inc. Medical procedures, devices and kits for the formation and removal of plug-forming compositions
US9775674B2 (en) * 2011-09-10 2017-10-03 Cook Medical Technologies Llc Suction lithotripsy apparatus, method and kit
US20130237967A1 (en) * 2011-09-10 2013-09-12 Cook Medical Technologies Llc Suction Lithotripsy Apparatus, Method and Kit
US9982791B2 (en) 2013-03-15 2018-05-29 Cook Medical Technologies Llc Bi-directional valve device for selective control of fluid flow through multiple converging paths
US9775631B2 (en) * 2013-03-15 2017-10-03 Boston Scientific Scimed, Inc. Gel sweeper for residual stone fragment removal
US9360124B2 (en) 2013-03-15 2016-06-07 Cook Medical Technologies Llc Bi-directional valve device for selective control of fluid flow through multiple converging paths
US20140276924A1 (en) * 2013-03-15 2014-09-18 Boston Scientific Scimed, Inc. Gel sweeper for residual stone fragment removal
US20150265297A1 (en) * 2014-03-21 2015-09-24 Terumo Kabushiki Kaisha Calculus retrieving/removing device and method
US20150265298A1 (en) * 2014-03-21 2015-09-24 Terumo Kabushiki Kaisha Calculus retrieving/removing device and method
US9539014B2 (en) * 2014-03-21 2017-01-10 Terumo Kabushiki Kaisha Calculus removing/retrieving device and method
US9610087B2 (en) * 2014-03-21 2017-04-04 Terumo Kabushiki Kaisha Calculus retrieving/removing device and method
US9615842B2 (en) * 2014-03-21 2017-04-11 Terumo Kabushiki Kaisha Calculus retrieving/removing device and method
US9636123B2 (en) * 2014-03-21 2017-05-02 Terumo Kabushiki Kaisha Calculus retrieving/removing device and method
US9517080B2 (en) * 2014-03-21 2016-12-13 Terumo Kabushiki Kaisha Calculus retrieving/removing device and method
US20150265295A1 (en) * 2014-03-21 2015-09-24 Terumo Kabushiki Kaisha Calculus retrieving/removing device and method
US20150265294A1 (en) * 2014-03-21 2015-09-24 Terumo Kabushiki Kaisha Calculus retrieving/removing device and method
RU2661014C2 (en) * 2014-09-02 2018-07-11 Нордсон Корпорейшн Device and method for fragmenting organo-mineral concretion
US9662097B2 (en) * 2015-03-31 2017-05-30 Terumo Kabushiki Kaisha Method for retrieving objects from a living body and expanding a narrowed region in the living body
US9636127B2 (en) * 2015-03-31 2017-05-02 Terumo Kabushiki Kaisha Method for retrieving objects from a living body
CN105147723A (en) * 2015-09-07 2015-12-16 山东赛克赛斯药业科技有限公司 Temperature-sensitive gel preparation, preparation method thereof and application of temperature-sensitive gel preparation to preventing transfer of calculus in lithotripsy

Also Published As

Publication number Publication date Type
US8998928B2 (en) 2015-04-07 grant
WO2005037062A3 (en) 2006-03-23 application
US20160015393A1 (en) 2016-01-21 application
US8409218B2 (en) 2013-04-02 grant
JP2007508116A (en) 2007-04-05 application
US20110060256A1 (en) 2011-03-10 application
JP4898447B2 (en) 2012-03-14 grant
EP1682014A4 (en) 2010-11-17 application
EP1682014A2 (en) 2006-07-26 application
US20170086849A1 (en) 2017-03-30 application
US20130172789A1 (en) 2013-07-04 application
WO2005037062A2 (en) 2005-04-28 application

Similar Documents

Publication Publication Date Title
Teichman et al. Holmium: YAG lithotripsy yields smaller fragments than lithoclast, pulsed dye laser or electrohydraulic lithotripsy
Mueller et al. Extracorporeal shock wave lithotripsy of ureteral stones: clinical experience and experimental findings
Basiri et al. Ultrasonographic versus fluoroscopic access for percutaneous nephrolithotomy: a randomized clinical trial
Teichman et al. Ureteroscopic management of ureteral calculi: electrohydraulic versus holmium: YAG lithotripsy
Watterson et al. Ureteroscopy and holmium: YAG laser lithotripsy: an emerging definitive management strategy for symptomatic ureteral calculi in pregnancy
Auge et al. In vitro comparison of standard ultrasound and pneumatic lithotrites with a new combination intracorporeal lithotripsy device
Delius et al. Biological effects of shock waves: kidney haemorrhage by shock waves in dogs—administration rate dependence
Mobley et al. Low energy lithotripsy with the Lithostar: treatment results with 19,962 renal and ureteral calculi
US7591996B2 (en) Ultrasound target vessel occlusion using microbubbles
Kellett et al. Percutaneous cholecystolithotomy
Schulze et al. The Swiss Lithoclast: a new device for endoscopic stone disintegration
Gupta Is the holmium: YAG laser the best intracorporeal lithotripter for the ureter? A 3-year retrospective study
US20100087798A1 (en) Systems, methods and devices for using a flowable medium for distending a hollow organ
US6547754B1 (en) Thrombolysis device
Cooper et al. Intraoperative and early postoperative complications of operative hysteroscopy
Adamek et al. Management of retained bile duct stones: a prospective open trial comparing extracorporeal and intracorporeal lithotripsy
US6936025B1 (en) Thrombolysis device
US20050147585A1 (en) Internal clamp for surgical procedures
Grasso et al. A 7.5/8.2 F actively deflectable, flexible ureteroscope: a new device for both diagnostic and therapeutic upper urinary tract endoscopy
Paterson et al. Stone fragmentation during shock wave lithotripsy is improved by slowing the shock wave rate: studies with a new animal model
Denstedt et al. The Swiss Lithoclast: a new device for intracorporeal lithotripsy
Bapat et al. Comparison of holmium laser and pneumatic lithotripsy in managing upper-ureteral stones
Ritchey et al. A case of pediatric ureteroscopic lasertripsy
Sackmann et al. Extracorporeal shock wave lithotripsy for clearance of bile duct stones resistant to endoscopic extraction
Drasler et al. Rheolytic catheter for percutaneous removal of thrombus.

Legal Events

Date Code Title Description
AS Assignment

Owner name: PLUROMED, INC., MASSACHUSETTS

Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNORS:SCHWARTZ, ALEXANDER;MCDOUGAL, W. SCOTT;REEL/FRAME:016010/0442;SIGNING DATES FROM 20041111 TO 20041113

AS Assignment

Owner name: THE GENERAL HOSPITAL CORPORATION, MASSACHUSETTS

Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNOR:MCDOUGAL, W. SCOTT;REEL/FRAME:035876/0079

Effective date: 20150618

Owner name: GENZYME CORPORATION, MASSACHUSETTS

Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNOR:PLUROMED, INC.;REEL/FRAME:035876/0059

Effective date: 20121217