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WO2000004909A2 - Agent anesthesique injectable contenant un gaz noble - Google Patents

Agent anesthesique injectable contenant un gaz noble Download PDF

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Publication number
WO2000004909A2
WO2000004909A2 PCT/EP1999/004849 EP9904849W WO0004909A2 WO 2000004909 A2 WO2000004909 A2 WO 2000004909A2 EP 9904849 W EP9904849 W EP 9904849W WO 0004909 A2 WO0004909 A2 WO 0004909A2
Authority
WO
WIPO (PCT)
Prior art keywords
injection
gas
xenon
anesthetic
gaseous
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.)
Ceased
Application number
PCT/EP1999/004849
Other languages
German (de)
English (en)
Other versions
WO2000004909A3 (fr
Inventor
Ralf Igelhorst
Peter Neu
Carsten Pilger
Fridtjof Schucht
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.)
Messer Griesheim GmbH
Original Assignee
Messer Griesheim GmbH
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Messer Griesheim GmbH filed Critical Messer Griesheim GmbH
Priority to AU54104/99A priority Critical patent/AU5410499A/en
Priority to EP99939999A priority patent/EP1100514A2/fr
Publication of WO2000004909A2 publication Critical patent/WO2000004909A2/fr
Publication of WO2000004909A3 publication Critical patent/WO2000004909A3/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K33/00—Medicinal preparations containing inorganic active ingredients

Definitions

  • the invention relates to anesthetic agents for administration by injection, which contain a noble gas, and devices for applying these anesthetic agents.
  • Anesthetics include inhalation anesthetics, e.g. As diethyl ether, nitrous oxide, cyclopropane and halothane, and injection anesthetics, e.g. B. ketamine, barbiturates.
  • inhalation anesthetics e.g. As diethyl ether, nitrous oxide, cyclopropane and halothane
  • injection anesthetics e.g. B. ketamine, barbiturates.
  • Xenon has been used as an inhalation anesthetic for many years. Compared to the laughing gas (N 2 O) common today, there are a number of medical advantages. However, the widespread introduction of xenon for anesthesia has so far been opposed by the much higher material costs.
  • xenon As an inhalation anesthetic, large amounts are required for a narcotic effect.
  • B. consumed a minimum of 15 liters of xenon in the closed ventilation system.
  • the concentration of xenon in a breathing gas for anesthesia is a maximum of 79 vol .-% to ensure an oxygen content of at least 21 vol .-%. Anesthesia is achieved, but this alone is not sufficient. Additional sedatives, intravenous anesthetics and analgesics have to be administered in addition. Muscle relaxants must also be used for certain interventions.
  • the known injection anesthetics have a number of disadvantages. These agents have only a slight pain-relieving effect, are only gradually broken down in the body or excreted via the liver and kidneys, usually have undesirable side effects and are difficult to control. To date, combinations of active substances have always been used for intravenous anesthesia.
  • the invention has for its object to provide a means for anesthesia that does not have the disadvantages mentioned.
  • the invention thus relates to an injection anesthetic which contains one or more lipophilic noble gases or a gas containing Iipophilic noble gas.
  • the injection anesthetic is, for example, a pure gaseous lipophilic noble gas, a mixture of lipophilic noble gases or gas mixtures which contain one or more lipophilic noble gases.
  • Lipophilic noble gases are argon, krypton, xenon and radon.
  • Argon, krypton or xenon, in particular xenon, are preferably suitable as an injection anesthetic or part of an injection anesthetic.
  • the invention is explained below using the example of xenon and xenon-containing gases, from which no restriction to xenon or xenon-containing gases can be derived and the information can be transferred to lipophilic noble gases.
  • the xenon gas used generally has the natural isotope composition.
  • the isotope composition of xenon can differ from the natural isotope composition.
  • the xenon gas is preferably used in high purity, as is customary for medical gases.
  • the xenon gas serves as a pure gas or in a mixture with other gases as an injection anesthetic or anesthetic.
  • xenon as an injection anesthetic can be administered as a pure gas into the bloodstream.
  • Gases containing xenon are gas mixtures containing xenon.
  • the gas mixtures preferably contain more than 50% by volume of xenon, particularly preferably more than 70% by volume of xenon, in particular more than 80% by volume of xenon.
  • the gas mixtures can contain one or more gases or gaseous substances at body temperature and normal pressure.
  • Gas mixtures that can be used are, for example, xenon-carbon dioxide gas mixtures.
  • the carbon dioxide content of such xenon-carbon dioxide gas mixtures is e.g. B. 1, 10, 20, 50 or 90 vol .-%.
  • the addition of a gas to the xenon can be very advantageous if little xenon is to be brought into the body.
  • the xenon content in the injection anesthetic or injection anesthetic can, for example, be 100% by volume when the anesthetic is initiated and can be reduced to maintain the anesthetic.
  • the gas composition of the injection anesthetic or injection anesthetic can be changed continuously or discontinuously during anesthesia.
  • the injection anesthetic is preferably a gaseous injection anesthetic or gaseous injection anesthetic.
  • the injection anesthetic can also be solid or liquid and contain gaseous xenon or xenon-containing gas.
  • Gaseous injection anesthetic is generally provided as a compressed gas in pressurized gas containers such as pressurized gas cylinders or pressure cans.
  • the gaseous injection anesthetic can also be provided in a container with a liquefied gas or gas mixture.
  • the gaseous injection anesthetic is typically injected into the body through a cannula or catheter connected to a gas source.
  • the injection is usually in a vein or artery.
  • the gas source contains or transports gaseous xenon or a gas containing xenon.
  • the gas source is e.g. B. a syringe, a gas balloon, a gas line, a gas hose, a gas pump or preferably a gas metering device.
  • the gaseous injection anesthetic or injection anesthetic is advantageously injected into the body using a gas metering device via a catheter.
  • the gas metering device is advantageously a precision gas metering device which is based, for example, on the principle of a piston gas pump.
  • catheters can be used as the catheter for the application of the gaseous injection anesthetic.
  • the catheters can have one or more openings (outlet openings) for dispensing the gaseous injection anesthetic.
  • the catheters can be straight or curved. Bent catheters can have a spiral shape. It is advantageous to use curved or spiral catheters with a plurality of openings which are arranged on the inside of the arc or the turns.
  • Outlet openings of cannulas or catheters in particular very advantageously have a small diameter, for. B. in the range of 50 to 1000 microns, preferably 50 to 700 microns, for generating microbubbles of xenon or xenon-containing gas in the blood.
  • a small diameter for. B. in the range of 50 to 1000 microns, preferably 50 to 700 microns, for generating microbubbles of xenon or xenon-containing gas in the blood.
  • To generate microbubbles of xenon or xenon-containing gas in the blood for. B. microcatheter suitable.
  • the injected xenon or gas containing xenon generally dissolves partially or completely in the blood.
  • Injection anesthetic in the blood is affected by the amount and rate of gas dosing (gas injection). According to the current, preliminary state of knowledge, it is assumed without being determined that the xenon which is undissolved in the blood, in particular in the form of microbubbles in the blood, is particularly effective in the case of intravenous or intra-arterial injection anesthesia.
  • the injection anesthetic is introduced into the bloodstream, for example by means of suitable devices such as microcatheters with a gas metering device, in such a way that microbubbles with xenon or xenon-containing gas form in the blood.
  • the microbubbles with injection anesthetic are therefore generated in situ (in the bloodstream).
  • microbubbles with injection anesthetic can be produced outside the body in a liquid, which are administered as a quasi liquid injection anesthetic with microbubbles made of xenon or xenon-containing gas.
  • Suitable liquids are e.g. B. blood or injectable, body-compatible liquids.
  • Body-compatible liquids are e.g. B. blood substitutes, e.g. B.
  • isotonic solutions such as physiological saline, Ringer's solution and Tyrode's solution or so-called plasma (volume) expander, these are viscous solutions of macromolecular substances such as dextrans, gelatin derivatives, starch derivatives, serum proteins or perfluorinated compounds such as fluorocarbons, perfluorinated Ethers and amines, optionally emulsified with polyethers.
  • liquids with smaller or smaller are preferably used Lipophilia is used, for example viscous, preferably aqueous solutions of macromolecular substances such as polysaccharides, peptides or proteins.
  • the preparation is advantageously carried out by partially or completely dissolving xenon or xenon-containing gas in the liquid under hyperbaric conditions, that is to say under pressure at a preferably reduced temperature (for example 10 ° C. to minus 10 ° C., preferably around 0 ° C.) . When the pressure is released, small and very small gas bubbles form.
  • Liquid injection anesthetics can be administered in doses, for example, by means of peristaltic pumps or conventional infusion pumps, wherein the xenon content and / or the infusion rate, preferably controlled, can be varied.
  • the liquid injection anesthetics can also be administered simply by means of an infusion bag / infusion line / catheter or by means of a syringe into the bloodstream.
  • the dispensing of the liquid injection anesthetic from an infusion bag can be controlled, for example, using a control valve in the hose line and a controller.
  • the injection anesthetic, gaseous or liquid, can also be supplied to the blood outside the body and the blood loaded with the injection anesthetic can be injected or infused into the body.
  • the xenon injected into the body is exhaled through the lungs.
  • the patient's exhaled gas (expiratory gas) is analyzed particularly advantageously during anesthesia and the xenon content measured in the expiratory gas or a corresponding measurement signal for monitoring the anesthetic or for controlling the dosage of injection anesthetic or injection anesthetic, in particular of gaseous injection anesthetic or injection anesthetic.
  • composition of the expiratory gas is advantageously tracked online with the aid of an analysis device such as a mass spectrometer, the measurement signal of the mass spectrometer, which corresponds to the xenon content or the content of another gas in the expiratory gas, being fed to a control device which doses the injection anesthetic by means of the gas metering device or another dosing device controls.
  • an analysis device such as a mass spectrometer
  • the measurement signal of the mass spectrometer which corresponds to the xenon content or the content of another gas in the expiratory gas
  • a control device which doses the injection anesthetic by means of the gas metering device or another dosing device controls.
  • Anesthetic agents are supplied, for example, analogously to the method described for inhalation anesthesia in WO 97/20591 (internal name MG 1970), to which reference is hereby made.
  • Anesthesia with injection anesthetic in particular gaseous injection anesthetic, can be influenced by separate injection into the bloodstream from a liquid, in particular a lipophilic liquid.
  • Lipophilic liquids are e.g. B. fat emulsions.
  • fat emulsions based on soybean oil / (3-sn-phosphatidyl) choline / glycerol / water are suitable, which are available for infusion under the name Intralipid (R) (Pharmacia & Upjohn GmbH, Er Weg).
  • the administration of the injection anesthetic can take place in combination with one or more additional pharmacologically active agents, namely as a component of the injection anesthetic and / or by separate administration of injection anesthetic and pharmacologically active agent.
  • An injection anesthetic can also be made from xenon or a xenon-containing gas and liquid.
  • the liquids usually contain water. Isotonic liquids are advantageous. A pH of the liquid in the range pH 6 to 8 is also advantageous.
  • the liquid is loaded with gas bubbles, preferably micro gas bubbles.
  • the liquid particularly advantageously contains an additive that stabilizes gas bubbles, e.g. B. an additive with one or more surfactants or emulsifiers.
  • Liquids with protein or protein mixtures can also advantageously be used as additives, e.g. B. an albumin solution.
  • Injection anesthetic from a liquid with xenon or a xenon-containing gas, e.g. B. in the form of gas bubbles, in particular micro gas bubbles can also be regarded as a liquid injection anesthetic or anesthetic.
  • Injected xenon or xenon-containing gases or xenon-containing liquids have been found to be sedative, analgesic, anti-inflammatory and muscle relaxant.
  • Xenon or gases containing xenon can therefore be used as gaseous injection sedation agents! (Sedative), as a gaseous injection analgesic, as a gaseous injection agent for inflammation therapy or injection anti-inflammation agent or as a gaseous injection agent for muscle relaxation (injection muscle relaxant).
  • liquids containing xenon can be used as injection sedatives (sedatives), as injection analgesics, as anti-inflammatory agents or as muscle relaxants.
  • the agents are administered in a pharmacologically effective amount.
  • the gas metering device is used to introduce nakose to a xenon gas flow of 60 ml / min. set. 30 ml xenon in 1 ml Pulses are injected intravenously into the patient through a catheter. After reaching a sufficient anesthetic depth, the xenon gas flow on the gas metering device is increased to 12 ml / min. reduced and every 10 seconds 2ml Xenon are administered pulsed intravenously to maintain. When the anesthesia ends, the xenon supply is stopped.
  • Xenon is exhaled through the lungs during the entire anesthetic.
  • the measurement of the xenon content in the patient's expiratory air, e.g. B. by means of mass spectrometry, enables precise monitoring of the injection anesthesia.

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Inorganic Chemistry (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Medicinal Preparation (AREA)

Abstract

L'invention concerne un agent anesthésique injectable qui contient un ou plusieurs gaz nobles lipophiles, par ex. de l'argon, du krypton ou du xénon, ou des mélanges gazeux renfermant un ou plusieurs gaz nobles lipophiles. Cet agent anesthésique injectable se présente sous forme gazeuse, liquide ou solide. Les agents anesthésiques liquides contiennent de préférence des bulles de gaz microscopiques renfermant un gaz noble lipophile. Cet agent anesthésique injectable est de préférence administré par voie intraveineuse ou intra-artérielle.
PCT/EP1999/004849 1998-07-23 1999-07-10 Agent anesthesique injectable contenant un gaz noble Ceased WO2000004909A2 (fr)

Priority Applications (2)

Application Number Priority Date Filing Date Title
AU54104/99A AU5410499A (en) 1998-07-23 1999-07-10 Injectable anaesthetic containing noble gas
EP99939999A EP1100514A2 (fr) 1998-07-23 1999-07-10 Agent anesthesique injectable contenant un gaz noble

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
DE19833014.6 1998-07-23
DE1998133014 DE19833014A1 (de) 1998-07-23 1998-07-23 Edelgashaltige Injektionsanästhesiemittel

Publications (2)

Publication Number Publication Date
WO2000004909A2 true WO2000004909A2 (fr) 2000-02-03
WO2000004909A3 WO2000004909A3 (fr) 2000-06-22

Family

ID=7874947

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/EP1999/004849 Ceased WO2000004909A2 (fr) 1998-07-23 1999-07-10 Agent anesthesique injectable contenant un gaz noble

Country Status (4)

Country Link
EP (1) EP1100514A2 (fr)
AU (1) AU5410499A (fr)
DE (1) DE19833014A1 (fr)
WO (1) WO2000004909A2 (fr)

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2002022116A1 (fr) * 2000-09-14 2002-03-21 Messer Griesheim Gmbh Agent anesthesique volatil au xenon
EP1570852A3 (fr) * 2000-09-14 2005-11-23 Air Liquide Deutschland GmbH Utilisation thérapeutique du xénon

Families Citing this family (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
AU5985900A (en) * 1999-07-19 2001-02-05 Michael Georgieff Novel spinal and epidural anaesthetic
WO2002045721A1 (fr) * 2000-12-04 2002-06-13 Uws Ventures Limited Complexes a base de gaz noble
DE10161251B4 (de) * 2001-12-13 2007-07-12 Air Liquide Deutschland Gmbh Schlafmittel mit Xenon
EP3035942B1 (fr) * 2013-08-19 2022-12-14 Schmidt, Klaus Michael Le gaz protecteur non anesthésique argon combiné à des liquides anesthésiques, et son utilisation pour la protection des organes

Family Cites Families (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5536241A (en) * 1990-12-05 1996-07-16 The General Hospital Corporation Methods and devices for relaxing smooth muscle contractions
US5099834A (en) * 1991-07-16 1992-03-31 Union Carbide Industrial Gases Technology Corporation Method for anesthesia
US5545396A (en) * 1994-04-08 1996-08-13 The Research Foundation Of State University Of New York Magnetic resonance imaging using hyperpolarized noble gases
DE69617719D1 (de) * 1995-10-20 2002-01-17 Air Liquide Pharmazeutische zusammensetzung von stickstoffmonoxid
DK0921807T3 (da) * 1996-08-27 2004-03-15 Messer Griesheim Gmbh Hydrogenholdigt lægemiddel
US5869538A (en) * 1996-11-26 1999-02-09 Research Foundation Of State University Of New York Method for enhancing transport of gases to tissues
DE19709704C2 (de) * 1997-03-10 1999-11-04 Michael Georgieff Verwendung einer flüssigen Präparation von Xenon zur intravenösen Verabreichung bei Einleitung und/oder Aufrechterhaltung der Anaesthesie

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2002022116A1 (fr) * 2000-09-14 2002-03-21 Messer Griesheim Gmbh Agent anesthesique volatil au xenon
EP1570852A3 (fr) * 2000-09-14 2005-11-23 Air Liquide Deutschland GmbH Utilisation thérapeutique du xénon
EP1908458A1 (fr) * 2000-09-14 2008-04-09 Air Liquide Deutschland GmbH Agent anesthésique volatile au xénon

Also Published As

Publication number Publication date
AU5410499A (en) 2000-02-14
WO2000004909A3 (fr) 2000-06-22
DE19833014A1 (de) 2000-01-27
EP1100514A2 (fr) 2001-05-23

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