Classifications

• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
  • A61B8/00—Diagnosis using ultrasonic, sonic or infrasonic waves
  • A61B8/48—Diagnostic techniques
  • A61B8/481—Diagnostic techniques involving the use of contrast agents, e.g. microbubbles introduced into the bloodstream
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K41/00—Medicinal preparations obtained by treating materials with wave energy or particle radiation ; Therapies using these preparations
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K49/00—Preparations for testing in vivo
  • A61K49/22—Echographic preparations; Ultrasonic imaging preparations
  • A61K49/222—Echographic preparations; Ultrasonic imaging preparations characterised by a special physical form, e.g. emulsions, liposomes
  • A61K49/223—Microbubbles, hollow microspheres, free gas bubbles, gas microspheres
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
  • A61N7/00—Ultrasound therapy
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
  • A61B17/00—Surgical instruments, devices or methods
  • A61B17/22—Implements for squeezing-off ulcers or the like on inner organs of the body; Implements for scraping-out cavities of body organs, e.g. bones; for invasive removal or destruction of calculus using mechanical vibrations; for removing obstructions in blood vessels, not otherwise provided for
  • A61B2017/22082—Implements for squeezing-off ulcers or the like on inner organs of the body; Implements for scraping-out cavities of body organs, e.g. bones; for invasive removal or destruction of calculus using mechanical vibrations; for removing obstructions in blood vessels, not otherwise provided for after introduction of a substance
  • A61B2017/22088—Implements for squeezing-off ulcers or the like on inner organs of the body; Implements for scraping-out cavities of body organs, e.g. bones; for invasive removal or destruction of calculus using mechanical vibrations; for removing obstructions in blood vessels, not otherwise provided for after introduction of a substance ultrasound absorbing, drug activated by ultrasound
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
  • A61B17/00—Surgical instruments, devices or methods
  • A61B17/22—Implements for squeezing-off ulcers or the like on inner organs of the body; Implements for scraping-out cavities of body organs, e.g. bones; for invasive removal or destruction of calculus using mechanical vibrations; for removing obstructions in blood vessels, not otherwise provided for
  • A61B2017/22082—Implements for squeezing-off ulcers or the like on inner organs of the body; Implements for scraping-out cavities of body organs, e.g. bones; for invasive removal or destruction of calculus using mechanical vibrations; for removing obstructions in blood vessels, not otherwise provided for after introduction of a substance
  • A61B2017/22089—Gas-bubbles

Definitions

• the invention relates to the use of bubble-containing media for shock wave and ultrasound therapy.
• An effective stone destruction is the electro-hydraulic stone destruction, in which a pressure wave is generated outside the body and is focused on the stone through the body tissue.
• a pressure wave is generated outside the body and is focused on the stone through the body tissue.
• waves are generated in liquid by excitation of a spark gap with a damped resonant circuit or with capacitor discharge.
• the spark gap is surrounded by a focusing reflector.
• wave generation is e.g. pulsed lasers, piezoelectric or electromagnetic elements.
• the waves can be focused, in addition to reflection on a semi-ellipsoid, by means of a parabolic arrangement of the energy sources or by bundling with an acoustic lens (F. Eisenberger et al. Urological Stone Therapy, Georg Thieme Verlag Stuttgart 1987 p. 25 ff. And the listed literature) .
• shock or ultrasonic waves are used as waves for therapy.
• the invention has for its object to use a means for therapy by means of shock waves and ultrasound with which the total irradiated energy per treatment can be reduced compared to the known methods by increasing the effectiveness at the site of stone destruction to relieve the patient.
• a suspension with microbubbles consisting of microparticles of a surface-active substance in a liquid carrier or
• the agent used can advantageously contain microparticles, the surfactant lecithins, polyoxyethylene fatty acid esters, glycerol polyethylene glycol ricinoleate, polyoxyethylene polyoxypropylene polymers, sucrose esters, xyloglycerides, saturated or unsaturated (C44C20) fatty alcohols, saturated or unsaturated (C4-C20) fatty acids Contain salts, mono-, di- and triglycerides, fatty acid esters as microparticles. It is also possible that the agent contains microparticles which contain soybean oil sucrose glyceride or polyethylene glycol sorbitan monostearate as the surfactant.
• Magnesium stearate, ascorbyl palmitate, sucrose monopalmitate, sucrose monostearate, sucrose distearate or butyl stearate as surface-active substances on average can be used as microparticles with particular advantage be included.
• the microbubble suspension contains the surfactant in a concentration of 0.001 to 5 percent by weight, preferably 0.04 to 1 percent by weight.
• the agent can preferably contain cyclodextrins, monosaccharides, disaccharides, trisaccharides, polyols or inorganic or organic salts in a concentration of 2 to 50 percent by weight, preferably 9 to 40 percent by weight.
• the agent may also contain microparticles which contain dextrose, maltose, galactose, lactose or ⁇ -cyclodextrin in a concentration of 2 to 50 percent by weight, preferably 9 to 40 percent by weight, as a non-surfactant solid.
• Suitable inorganic or organic salts are sodium chloride, sodium citrate, sodium acetate or sodium tartrate.
• the smock used as a physiologically acceptable liquid carrier water, physiological electrolyte solution, aqueous solution of mono- or polyhydric alcohols or polyether alcohols or aqueous solution of a mono- or disaccharide or Ringer's solution or Tyrode solution or an aqueous solution of maltose, dextrose , Lactose or galactose.
• the liquid carrier can particularly advantageously contain glycerol, polyethylene glycol or propylene glycol methyl ether.
• physiological saline can also be contained in the agent as a physiologically compatible liquid carrier.
• an agent used according to the invention which contains microparticles of maltose, dextrose, lactose or galactose in a liquid carrier of water, a physiological electrolyte solution such as 0.9% aqueous sodium chloride solution, Ringer's solution or Tyrode solution or an aqueous one Solution of maltose, dextrose, lactose or galactose can contain, without the addition of viscosity-increasing substances such as propylene glycol, a good effect enhancement in shock wave and ultrasound therapy.
• the agent used according to the invention can contain microparticles of lactose in up to 25% (weight percent) aqueous lactose solution.
• the agents used according to the invention can also contain microparticles of galactose in up to 20% aqueous galactose solution or microparticles of galactose in water.
• the agent contains microparticles of a mixture of butyl stearate and galactose in water or a mixture of soybean oil sucrose. contains glyceride and galactose in water or polyethylene glycol sorbitan monostearate and galactose in physiological saline or oleic acid and galactose in physiological saline.
• an agent used according to the invention is a liquid solution with microbubbles, consisting of the mixture of 0.01 to 10 percent by weight of a surfactant or surfactant mixture with an aqueous or water-miscible carrier liquid and the mixture of 0.5 up to 50 percent by weight of a viscosity-increasing substance or a mixture of substances in an aqueous or water-miscible carrier liquid, the two mixtures being present separately or combined.
• a means for shock wave and ultrasound therapy can be used with particular advantage, consisting of a mixture of 0.01 to 10 percent by weight of a surfactant or surfactant mixture in an aqueous or water-miscible carrier liquid, the 0.05 to 5 percent by weight of a physiologically compatible carboxylic acid Salt contains and the mixture of 0.5 to 50 percent by weight of a viscosity-increasing substance or a substance mixture with an aqueous or water-miscible carrier liquid which contains an amount equivalent to the carboxylic acid salt physiologically compatible acid.
• Sodium hydrogen carbonate and potassium hydrogen are particularly found as physiologically compatible carboxylic acid salts carbonate application. Lactic acid, citric acid and pyruvic acid are particularly mentioned as physiologically compatible acids.
• nonionic surfactants lecithins, lecithin fractions and their modification products, polyoxyethylene fatty acid esters such as polyoxyethylene fatty alcohol ethers, polyoxyethylated sorbitan fatty acid esters, glycerol polyethylene glycol oxystearate, glycerol polyethylene glycol rhizinoleate, ethoxylated soy ethylene oxide polymers, ethoxylated ethoxylated ethoxylated ethoxylated ethoxylated ethoxylated ethylene oxide polymers, with molecular weights 6800-8975, 13300 and 16250 are preferred.
• Possible ionic surfactants are: quaternary ammonium base, sodium lauryl sulfate, sodium dioctyl sulfosuccinate.
• Possible viscosity-increasing substances are mono- or polysaccharides such as glucose, levulose, galactose, lactose, sorbitol, mannitol, xylitol, sucrose or dextrans, cyclodextrins, hydroxyethyl starch and polyols. Glycerol, polyglycols, inulin and 1,2-propanediol are used as polyols.
• protein-like substances amino acids or blood substitutes such as, for example, plasma proteins, gelatin, oxypolygelatin and gelatin derivatives or mixtures thereof are also used.
• the concentration of these substances mentioned in the solution can be 0.5 to 50 percent by weight, the maximum concentration also depending on the solute.
• glucose or lactose at a concentration of 0.5 to 50 percent by weight can be used, whereas gelatin has a preferred concentration of 0.5 to 2 percent by weight.
• the oxypolygelatin is preferably used in a concentration of 0.5 to 10 percent by weight.
• surfactants which at the same time increase the viscosity, such as, for example, polyoxyethylene-polyoxypropylene polymers with the molecular weight from 4750 to 16250.
• the concentration of the surfactants with a viscosity-increasing effect is 1 to 20 percent by weight, preferably 3 to 10 percent by weight.
• the surfactant or surfactant mixture is preferably dissolved in a carrier liquid in the presence of the viscosity-increasing substance or substance mixtures.
• Water can be used as the carrier liquid or aqueous solutions which are physiologically compatible, such as, for example, physiological electrolyte solutions such as physiological saline, can be mixed with water or polyhydric alcohols, Ringer's solution, Tyrode's solution or the aqueous solutions of sodium chloride, calcium chloride, sodium hydrogen carbonate, sodium citrate, sodium acetate or sodium tartrate or salt solutions, as are usually used as infusion solutions, or mixtures thereof.
• physiological electrolyte solutions such as physiological saline
• the abovementioned means are used for any form of extracorporeal shock wave lithotripsy (ESWL). They are excellent for reinforcing the crushing of kidneys and gallstones.
• the agents are transported to the target organs by retrograde or antegrade application.
• the agent is introduced retrograde into the kidney, the urine must first be withdrawn via a catheter that is introduced into the kidney via the ureter. After the urine has been removed, the agent (2 - 50 ml depending on the volume of the kidney) is introduced into the kidney in order to be removed from the kidney after a short residence time of approx. 0.5 to 2 minutes. The kidney is then filled with a physiologically compatible solution. Irradiation using elastomechanical vibrations (shock waves, ultrasonic waves) for the purpose of stone destruction can now join.
• the means is brought into the immediate vicinity of the stone in the case of retrograde working.
• the stone surface is specifically provided with the middle solution (volume: 0.1 - 5 ml).
• the stone is deliberately coated with the middle solution (volume of the applied solution: 1 - 5 ml). Irradiation by elastomechanical vibrations can now follow.
• the agent is introduced into the kidney using a puncture needle and removed after a short residence time (0.5-2 minutes) and then exposed to the vibrations.
• the cavities of the target organs for example kidney, bile
• the desired success of lithotripsy is not achieved.
• the numerous microbubbles absorb and scatter the radiated elastomechanical vibration on the stones. The incident waves do not reach the destination, the stone, with sufficient energy.
• the properties of the agents cause the microbubbles of the agent, for example by adhesive forces on the upper, in a procedure as described under a) stick to the surface of the stones.
• the subsequent displacement by means of a physiologically compatible solution displaces only the agent from the organ space; the microbubbles adhering to the stones remain in sufficient quantity.
• stones that are covered with a microbubble layer and that are (stone + bubbles) in the physiologically compatible solution are then stones that are covered with a microbubble layer and that are (stone + bubbles) in the physiologically compatible solution. If the elastomechanical vibrations are now radiated in, the energy of these vibrations is absorbed by the bubbles adhering to the stone and used to break up the stone.
• Treatment of gallstones is possible in an analogous manner, for example, using antegrade or retrograde puncture using known methods.
• a human gallstone is introduced into the second focus of the elipsoid in a sample vessel.
• the sample vessel is then filled with the agent (20 ml of a 25% galactose suspension in water).
• the galactose suspension is then removed from the sample vessel by means of a plunger and the sample vessel is filled with 20 ml of physiological saline.
• the concrement in the sample vessel is now exposed to the shock waves. After only nine impacts, this stone fell into many small fragments.
• the experimental set-up is the same as in Example 1. However, the gallstone (same size as in Example 1) was not treated with the galactose agent, but was immediately introduced into the physiological saline solution. After 100 impacts of the same energy applied to the stone, no stone fragmentation was achieved.

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• 1987
  • 1987-12-02 DE DE19873741199 patent/DE3741199A1/de active Granted
• 1988
  • 1988-12-02 EP EP88730269A patent/EP0322350A1/de active Pending
  • 1988-12-02 WO PCT/DE1988/000751 patent/WO1989005160A1/de not_active Ceased
  • 1988-12-02 JP JP1500022A patent/JPH03505723A/ja active Pending
  • 1988-12-02 EP EP19890900109 patent/EP0397671A1/de not_active Withdrawn

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